A-ONE PHARMACY COLLEGE

M. PHARM SEM- I

PHARMACEUTICS –I (MPH105P)

PRACTICAL JOURNAL
PART B

YEAR: - 2024-2025

DEPARTMENT OF PHARMACEUTICS (20)

Approved by PCI New Delhi

AFFILIATED WITH GUJARAT TECHNOLOGICAL UNIVERSITY-A’BAD
SNME Campus, Naroda-Dahegam Road, Anasan, Ahmedabad-382330
Ph: 02718-240232 Fax: 02718-240231 Website: www.snme-campus.org
Email: [email protected]
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INDEX

Sr Practical Page Date Signature

no. no.
1 To prepare standard calibration curve of given active
pharmaceutical ingredient (API) ( Ranolazine) 2

2 To perform In-vitro dissolution profile of CR/

SR marketed formulation. 6

3 Formulation and evaluation of sustained release

matrix tablets. 11
4 Formulation and evaluation osmotically
19
controlled DDS.
5 Preparation and evaluation of Floating DDS-
hydro dynamically balanced DDS. 23

6 Formulation and evaluation of Muco adhesive

tablets (Ranolazine). 27

7 Formulation and evaluation of trans dermal

patches (Ranolizine). 34

8 To carry out pre-formulation studies of powder &

37
tablets.
9 To study the effect of compressional force on
tablets disintegration time. 44

10 To study the effect of binders on dissolution of

a tablet. 49

11 To plot Heckal plot, Higuchi and peppas plot and

determine similarity factors 55

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Practical No. 1
AIM: To prepare standard calibration curve of given Ranolazine
active pharmaceutical ingredient (API)

1.0 INTRODUCTION
In analytical chemistry, a calibration curve is a general method for determining the concentration
of a substance in an unknown sample by comparing the unknown to a set of standard samples of
known concentration. The construction of a curve or straight line by plotting observed or
experimental data on a graph is an important method of visualizing relationships between
variables.

Fitting a curve to the points on a graph implies that there is some sort of relationship between the
variables X and Y. Moreover, the relationship is not confined to isolated points but is a continuous
function of X and Y. In many cases, a hypothesis is made concerning the relationship between the
variables X and Y. Then an empirical equation is formed that best describes the Hypothesis. This
empirical equation must satisfactorily fit the experimental or observed data.However, it may be
possible to arrange or transform the data to express the relationship between the variables as a
straight line. Straight lines are very useful for accurately predicting values for which there are no
experimental observations.

The general equation of a straight line is…

y = mx + c
Where, y = dependent variable
m = slope.
x = independent
variable. c= intercept

2.0 MATERIAL & METHOD

2.1 Material
Active pharmaceutical ingredient (Ranolazine) Gift sample from XYLOPIA Labs., Ahmedabad,
0.1N HCL (Hydrochloric Acid)

2.2 Method
By Dilution using 0.1N HCL (Hydrochloric acid)

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2.3 Solubility of Ranolazine

• As per literature Review, the solubility of Ranolazine as follows.
• Easily soluble in acid
• Very slightly soluble in water
• Slightly soluble in ethyl acetate, isopropanol
• Sparingly soluble in ethanol, acetone, acetonitrile

2.4 Preparation of standard curve

Ranolazine was spectrophotometrically (UV 1800, Shimadzu) measured at 272 nm by using 0.1N
pH 1.2 acid buffer. Weighed accurately 100mg of Ranolazine and transferred to a 100ml
volumetric flask. Volume was made with 0.1N Hydrochloric Acid. It was mixed well to get a
concentration of 1000 μg/ml. From the stock Solution, 10 ml was withdrawn & dilute to 100ml with
respective Medias to get 100μg/ml. From this secondary stock 0.5 to 5 ml, was taken separately and
made up to 10ml with buffer, to produce a concentration range of 5-50 μg/ml. The
absorbance was measured at 272 nm in UV- spectrophotometer Using 0.1N HCl as blank .plot the
graph between the concentration on X-axis And absorbance on Y-axis get the calibration curve of
the drug.

2.4.1 Procedure
2.4.1.1 Preparation of 0.1N HCl (37% HCl):-9.9ml in 1000ml
2.4.1.2 Dilution
Six different dilutions were used to minimise error. They are as per follow
(A)
100mg in 100ml VF (1000µg/ml)
Take above solution 10ml in 100ml VF (100µg/ml)
2ml in 10ml VF 4ml in 10ml VF 6ml in 10ml VF 8ml in 10ml VF 10ml in 10ml VF
(20µg/ml) (40µg/ml) (60µg/ml) (80µg/ml) (100µg/ml)

(B)
200mg in 100ml VF(2000µg/ml)
Take above solution 5ml in 100ml VF(100µg/ml)
2ml in 10ml VF 4ml in 10ml VF 6ml in 10ml VF 8ml in 10ml VF 10 ml in 10ml VF
(20µg/ml) (40µg/ml) (60µg/ml) (80µg/ml) (100µg/ml)

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(C)
400mg in 100ml VF(4000µg/ml)
Take above solution 2.5ml in 100mlVF (100µg/ml)
2ml in 10ml VF 4ml in 10ml VF 6ml in 10ml VF 8ml in 10ml VF 10ml in 10ml VF
(20µg/ml) (40µg/ml) (60µg/ml) (80µg/ml) (100µg/ml)
(D)
100mg in 50ml VF(2000µg/ml)
Take above solution 5ml in 100ml VF(100µg/ml)
2ml in 10ml VF 4ml in 10ml VF 6ml in 10ml VF 8ml in 10ml VF 10ml in 10ml VF
(20µg/ml) (40µg/ml) (60µg/ml) (80µg/ml) (100µg/ml)
(E)
100mg in 200ml VF(500µg/ml )
Take above solution 20ml in 100ml VF (100µg/ml)
2ml in 10ml VF 4ml in 10ml VF 6ml in 10ml VF 8ml in 10ml VF 10ml in 10ml VF
(20µg/ml) (40µg/ml) (60µg/ml) (80µg/ml) (100µg /ml)
(F)
100mg in 500ml VF(200 PPM)
10ml in 100ml 20ml in 100ml 30ml in 100ml40ml in 100ml VF 100ml in 100
(20µg/ml) (40µg/ml) (60µg/ml) (80µg/ml) (100µg/ml)

3.0 RESULT
3.1 Observation table
CONC. ABS 1 ABS 2 ABS 3 ABS 4 ABS 5 ABS 6 AVG SD
(µg/ml)

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4.0 CONCLUSION:

5.0 REFERENCES
1. Pittala B, Kumar N, Kakkerla A, Murthy SV. Formulation and Evaluation of Ranolazine
Extended-Release Tablets by using pH-Dependent and Independent polymers.
2013;4(6):1164-1171.
2. Services M. Department of health & human services. 2002.

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Practical No. 2
AIM: To perform In-vitro dissolution profile of CR/ SR marketed formulation.

1.0 INTRODUCTION:
The aim of the study was to perform In-vitro dissolution profile of CR/ SR marketed formulation. Here
marketed formulation Ranolaz® (Torrent) was taken (ranolazine tablet-500 mg); generally it can be
use in chest pain (Angina) due to prolonged therapeutic effect by continuously release medication over
an extended period of time after single dose. Drug release study was evaluated for 24 hours in 0.1 N
HCL dissolution medium at 37±0.5 0C temperature. As per USFDA the USP apparatus 2 (paddle) was
used. Here studied drug release for 24 hours and compare it with test
formulation of ranolazine. In that case the marketed product and test formulation showed
dissolution profile relatively similar & marketed formulation don’t control burst effect initially

“Dissolution is the process by which a solid substance enters the solvent phase to yield a solution’’.
It is a rate limiting step for the absorption of drugs

Sustained release – to achieve a prolonged therapeutic effect by continuously releasing medication

over an extended period of time after single dose.

In vitro dissolution testing for optimization of drug release from the formulation. Also employed
as a quality control (QC) in R & D, to detect the influence of critical manufacturing variables and
in comparative studies for in vitro in vivo correlation (IVIVC)

Dissolution from drug particles mainly reflects the effect of solubility and particle size, which are
largely properties of the drug raw material, but can also be influenced significantly by processing
and formulation. Drug dissolved also play a major role, as described by the Noyes–Whitney
equation, which describes the flux of drug into solution as a mathematical relationship between
these factors.

Dissolution tests are used nowadays in the pharmaceutical industry in a wide variety of applications:
to help identify which formulations will produce the best results in the clinic, to release products to
the market, to verify batch-to-batch reproducibility, and to help identify whether changes made to
formulations or their manufacturing procedure after marketing approval are likely to affect the
performance in the clinic. Further, dissolution tests can sometimes be implemented to help determine
whether a generic version of the medicine can be approved or not.

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2.0 DISSOLUTION SPECIFICATIONS

Dissolution parameters Specification

Drug name Ranolazine tablet

Marketed name Ranolaz
Temperature 37± 0.5 ◦C
Speed of rotation 50 rpm
USP apparatus Type 2 (paddle)
Medium 0.1 N HCL
Volume 900 ml
Sampling times (hrs) Interval of 1 hour for 24 hours
Dissolution tester Dissolution tester (USP) TDT-08L

3.0 MATERIALS & METHODS:

Ranolazine tablet (500 mg), dissolution rate test apparatus, distilled water, 0.1N HCL, Wattman
filter paper, UV VIS apparatus, glasswares

3.1 Procedure:
After interval of 1 hour for 24 hours a suitable volume (~ 5ml) of the medium was withdrawn and
filtered.. Absorbance in UV was taken of filtered sample, if the reading was not in range of the
calibration curve then dilute with suitable volume of same solvent. Measure the absorbance of the
resulting solution at the maximum at about 272nm. Calculate the drug concentration from y=mx+ C
(slope of standard curve of ranolazine) and find out the % drug release or % drug dissolved. Plot a
graph of time Vs % drug release. Also calculate the similarity and dissimilarity factors.

4.0 EVALUATION: similarity and dissimilarity

factor Similarity Factor: -

Dissimilarity Factor: -

These fit factors directly compare the difference between % drug dissolved per unit time for a test
and a marketed product. The fit factors are denoted f1 (dissimilarity) and f2 (similarity) where n

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is the number of dissolution sample times, and Rt and Tt are the individual or mean % dissolved
at each time point, t, for the marketed and test dissolution profiles, respectively.

5.0 RESULTS:
5.1 Observation table
Time Avg Conc(mc Dilution Conc* (900*conc.) Amt. of % %
(hrs) absorb g/ml) Dilution amt. of Drug Drug Drug
ance drug Release( Relea Rele
release mg/ml) se ase

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5.2 COMPARE WITH LAB FORMULATION

Time(h Market HPMC HPMC HPMC HPMC HPMC HPMC
rs) ed K4M(50 K4M(100 K15M K15M K100M(50 K100M(100
mg) (F1) mg) (F2) (50mg)( (100mg)( mg) (F5) mg) (F6)
F3) F4)

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Table F1 & F2 value
Evaluation Marketed Marketed Marketed Marketed Marketed Marketed

& & HPMC & HPMC & HPMC & HPMC & HPMC

HPMC K4M(100 K15M(50 K15M(100 K100M(50 K100M(100

K4M(50 mg) mg) mg) mg) mg)
mg) (F2) (F3) (F4) (F5) (F6)
(F1)
F1(dissimila
rity)
F2(similarit
y)

5.3 CONCLUSION:

6.0 REFERENCES:
1.Bettini, R. (1994). Pharmaceutical dissolution testing. (J. D. & J. Kramer), Journal of Controlled
Release (Vol. 32). Tylor & Francis. https://doi.org/10.1016/0168-3659(94)90064-7
2 . Administration, F. and D., & Silver Spring, M. 20993. (2013). Department of health &
human services. DEPARTMENT OF HEALTH & HUMAN SERVICES, (Reference ID:
3348461).

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Practical No. 3
AIM: Formulation and evaluation of Sustained Release Matrix
Tablet

1.0 INTRODUCTION: -

Ranolazine is novel drug used in treatment of chronic heart disease such as angina. It has
antianginal effect that does not depend upon reduction in rate or blood pressure. Ranolazine
inhibits persistent or late inward sodium current (INa) in heart muscle in a variety of voltage-gated
sodium channels. Inhibiting that current leads to reductions in elevated intracellular calcium levels.
This in turn leads to reduced tension in the heart wall, leading to reduced oxygen requirements for
the muscle. The QT prolongation effect of ranolazine on the surface electrocardiogram is the result
of inhibition of IKr, which prolongs the ventricular action potential. Ranolazine also exhibits its
effects on the delayed rectifier current (hERG/IKr Potassium channels), it readily stimulates
myogenesis, it reduces a pro-oxidant inflammation/oxidative condition, and activates the calcium
signalling pathway. Ranolazine prolongs the action potential duration, with corresponding QT
interval prolongation on electrocardiography, blocks the INa current, and prevents calcium
overload caused by the hyperactive INa current, thus it stabilizes the membrane and reducing
excitability.

Ranolazine shows high pH dependent solubility, it is freely soluble in aqueous solutions having
pH below 4.5 and then, as the pH increases solubility of the drug decreases dramatically,
furthermore Ranolazine has a short half-life 7 hrs, the acid solubility property of Ranolazine
results in rapid drug absorption and clearance, causing large and undesirable fluctuation in
plasma concentration and short duration of action, thus necessitating frequent oral administration
for adequate treatment. In order to maintain plasma drug concentration in the body twice daily
formulation of Ranolazine is needed for better control of drug release and therapeutic activity up
to 24 hrs.
Matrix tablets are providing the promising way to decrease the side effect of drug by preventing
the fluctuation of therapeutic concentration of the drug in the body.

• By this the frequency of dose to be administered is reduced by two-fold so side effects of the
drug may be reduced and in turn the patient compliance may also increase.
Hydrophilic matrix systems are the most popular among different technologies used in controlled
drug delivery because of the simplicity of formulation, ease of manufacturing, low cost, FDA
acceptance, and applicability to drugs with wide range of solubility Hydroxypropyl
methylcellulose (HPMC), which is commonly used in hydrophilic matrix drug delivery systems,
is mixed with alkyl hydroxyalkyl cellulose ether containing methoxyl and hydroxypropyl groups.
The hydration rate of HPMC increases with an increase in the hydroxypropyl content. HPMC has
been found to be a very versatile material for the formulation of soluble matrix tablets. It is widely
accepted pharmaceutical excipients and is included in all major compendia. Because HPMC is
available in a wide range of molecular weight. Due to this effective control of gel viscosity is
easily achieved.

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The present investigation aims at the design, development and optimization of controlled release
tablet of a Ranolazine, by using different grades of HPMC. The drug release profile of the tablets
was to compare with the drug release profile of marketed formulation for the selection of optimized
formulation.

2.0 MATERIALS & METHODS: -

Ranolazine (Xylopia Pharma Lab., Ahmedabad, India), Hydroxypropyl cellulose
(HPMCK4M, HPMCK15M, HPMCK100M) (Otto, Chemicals Pvt. Ltd.), Microcrystalline
cellulose (MOLYCHEM LTD., Mumbai, India), Magnesium stearate (Thrien Laboratory,
Ahmedabad, India), Talc (MOLYCHEM LTD., Mumbai, India).

2.1. Methods: -
2.1.1Preparation of Ranolazine tablets:
Matrix tablets of Ranolazine with other excipients were prepared by direct compression. The
weight of Ranolazine was kept constant in all the prepared tablets at 100mg/tablet. Different
viscosity grades of HPMC namely HPMC K4M, HPMC K15M, HPMC K100M were chosen
as polymeric matrix materials.
Micro crystalline cellulose (MCC) was selected as tablet diluent for increasing the
compressibility and flowability of the ingredients as well as to maintain the tablets at constant
weight of 120 mg. Magnesium stearate was used as a lubricant at concentration of 2% by
weight of tablet. To make powder mixtures, the drug, polymer and MCC were thoroughly
mixed for 30 min by means of pestle and mortar. This powder mixture was then lubricated
with magnesium stearate then compressed into tablets in 6 mm rotary tablet punching
machine. The force of compression was adjusted so that hardness of all the prepared tablets
ranges from 5.0-6.0 kg/cm. The detailed compositions of the prepared matrix tablets
formulations are given in (Table 1).

Table1: The Formula for Preparation of Matrix Tablet of Ranolazine

Ingredients(mg/tab) Formulation Code

F1 F2 F3 F4 F5 F6

Ranolazine 100 100 100 100 100 100

HPMC K4M 50 100 - - - -
HPMC K15M - - 50 100 - -
HPMC K100M - - - - 50 100
Micro Crystalline Cellulose PH101 22 22 22 22 22 22
Magnesium Stearate 2 2 2 2 2 2
Talc 1 1 1 1 1 1

2.2. Evaluation of prepared tablets:

2.2.1. Hardness test:
The crushing strength (Kg/cm2) of tablet was determined by using Monsanto hardness tester.

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2.2.2. Friability test:

This was determined by weighing 10 tablets after dusting, placing them in the friabilator (Roche
friabilator) and rotating vertically at 25 rpm for 4min. After revolutions the tablets were dedusted
and weighed again the percent friability was calculated by the formula: -

%F= {1-Wt/W} ×100

2.2.3. Uniformity of weight:
20 tablets were selected at random and weighed individually. The average weight of each of
tablet was calculated. Individual weights of the tablets were compared with the average weight.
Since the tablets weighed mg, I.P specifies that the tablets pass the test if not more than two of
the individual weights deviate from the average weight by more than 5%.
2.2.4. Thickness and diameter:
Five tablets were randomly selected for the determination of thickness and diameter with the
help of Vernier calipers apparatus.
2.2.5. Determination of swelling behavior:
The swelling-eroding behavior of matrix tablets was determined using the method described by
40Al-Taani and Tashoush. One matrix tablet was weighed and placed in a dissolution apparatus.
The swollen weights of tablets were calculated after placing the mixture in a vacuum oven at
C for 24 h.∗100Thefollowing formula was used for calculating %
swelling: % Swelling =
where, S is the weight of the matrix after swelling and T is the initial
weight of the matrix.
2.2.6. In vitro dissolution study
After interval of 1 hour for 24 hours a suitable volume (~ 5ml) of the medium was withdrawn and
filtered. Absorbance in UV was taken of filtered sample, if the reading was not in range of the
calibration curve then dilute with suitable volume of same solvent. Measure the absorbance of the
resulting solution at the maximum at about 272nm. Calculate the drug concentration from y=mx+ C
(slope of standard curve of ranolazine) and find out the % drug release or % drug dissolved. Plot a
graph of time Vs % drug release. Also calculate the similarity and dissimilarity factors.

3.0. RESULTS & DISCUSSION:

The results of Post Compressional Parameters of the formulation formed are as shown in following
table: -
3.1. % Swelling:
Physicochemical parameters of sustained release matrix tablet of Lornoxicam
Formulation Code Hardness Thickness (mm) Friability (% Weight variation
(kg/cm2) loss) (mg)
F1
F2
F3
F4
F5
F6

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Formulation % swelling
F1
F2
F3
F4
F5
F6

3.2. Observation Table of In- Vitro Dissolution Studies: -

Polymer: HPMC K4M - 50mg in 100mg Tablet. (2:1) – F1
Sr Time Absorbance Conc Dilution Conc*Dilution Amt of Amt. of %
No. (hrs) (µg/ml) Drug Drug Drug
Release Release Release
(µg/ml) (µ/ml)
1
2
3
4
5
6
7
8
9
10
11
12
13
14

Polymer: HPMC K4M – 100mg in 100mg/tab. (1:1) – F2

Sr Time Absorbance Conc Dilution Conc*Dilution Amt of Amt. of %
No. (hrs) (µ g/ml) Drug Drug Drug
Release( Release Release
µ g/ml) (mg/ml)
1
2
3
4
5
6
7
8
9
10
11
12
13
14

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Polymer: HPMC K15M - 50mg in 100mg Tablet. (2:1) – F3

Sr Time Absorbance Conc Dilution Conc*Dilution Amt of Amt. of %
No. (hrs) (mcg/ml) Drug Drug Drug
Release Release Release
(mcg/ml) (mg/ml)
1
2
3
4
5
6
7
8
9
10
11
12
13
14

Polymer: HPMC K15M – 100mg in 100mg/tab. (1:1) – F4

Sr Time Absorbance Conc Dilution Conc*Dilution Amt of Amt. of %
No. (hrs) (µ g/ml) Drug Drug Drug
Release Release Release
(µ g/ml) (mg/ml)
1
2
3
4
5
6
7
8
9
10
11
12
13
14

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Polymer: HPMC K100M - 50mg in 100mg Tablet. (2:1) – F5

Sr Time Absorbance Conc Dilution Conc*Dilution Amt of Amt. of %
No. (hrs) (µ g/ml) Drug Drug Drug
Release Release Release
(µ g/ml) (mg/ml)
1
2
3
4
5
6
7
8
9
10
11
12
13
14

Polymer: HPMC K100M – 100mg in 100mg/tab. (1:1) – F6

Sr Time Absorbance Conc Dilution Conc*Dilution Amt of Amt. of %
No. (hrs) (µ g/ml) Drug Drug Drug
Release Release Release
(µ g/ml) (mg/ml)
1
2
3
4
5
6
7
8
9
10
11
12
13
14

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3.3 Comparative Release profile of formulations containing different polymers and

Marketed Formulation (Ranolaz).

Time Marketed HPMC HPMC HPMC HPMC HPMC HPMC

(hrs) K4M K4M K15M K15M K100M K100M
(50mg) (100mg) (50mg) (100mg) (50mg) (100mg)

Chart Title
120
100
80
60
40
20
0
0 5 10 15 20 25 30

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% Drug release Marketed % Drug release HPMC K4M(50mg)

% Drug release HPMC K4M(100mg) % Drug release HPMC K15M(50mg)

% Drug release HPMC K15M(100mg) % Drug release HPMC K100M(50mg)

% Drug release HPMC K100M(100mg)

Release parameters of the tablet formulations are summarized as in Tables. Ranolazine release
from the prepared tablets was slow, spanning a period of 24 h and rested on the grade of the
controlled release polymer. A study was undertaken to determine the release profile of
Ranolazine matrix tablets with different viscosity grades of HPMC and thereby select a suitable

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polymer. HPMC K4M, HPMC K15M and HPMC K100M were selected for formulation and their
release profile compared with marketed formulation Ranolaz.
The result indicates that tablet formulation F2(HPMC K4M), F4(HPMC K15M) and F6 (HPMC
K100M) released 31.44 %, 28.23% and 26.94% at the end of 1 hour and 95.60 %, 95.86% and
94.32% at the end of 24hour.

4.0. CONCLUSION: -

5.0. REFRENCES:

1.Sharma PR, Lewis SA. Design and in vitro/in vivo evaluation of extended release matrix
tablets of nateglinide. J Young Pharm. 2013;5(4):167-172. doi:10.1016/j.jyp.2013.11.003.

2.Bettini, R. (1994). Pharmaceutical dissolution testing. (J. D. & J. Kramer), Journal of Controlled
Release (Vol. 32). Tylor & Francis. https://doi.org/10.1016/0168-3659(94)90064-7

3. Administration, F. and D., & Silver Spring, M. 20993. (2013). Department of health &human
services. DEPARTMENT OF HEALTH & HUMAN SERVICES, (Reference ID: 3348461).

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Practical No. 4
AIM: PREPARATION AND EVALUATION OF OSMOTIC
CONTROLLED DRUG DELIVERY SYSTEM OF RANOLAZINE
1.0 INTRODUCTION

Osmotically controlled drug delivery system, deliver the drug in a large extent and the delivery
nature is independent of the physiological factors of the gastrointestinal tract and these systems
can be utilized for systemic as well as targeted delivery of drugs.
Osmotically controlled oral drug delivery systems utilize osmotic pressure for controlled delivery of
active agents. Deliver the API at predetermined zero order rate for a prolonged period of time so these
are used as the standard dosage forms for the constant delivery of contents.
Once the tablet comes in contact with the aqueous environment, the water-soluble component
dissolves, and an osmotic pumping system results. Subsequently, water diffuses into the core
through the microporous membrane, setting up an osmotic gradient and thereby controlling the
release of the drug.
Osmosis can be defined as the spontaneous movement of a solvent from a solution of lower solute
concentration to a solution of higher solute concentration through an ideal semipermeable
membrane, which is permeable only to the solvent but impermeable to the solute. The pressure
applied to the higher-concentration side to inhibit solvent flow is called the osmotic pressure.
Vant Hoff identified an underlying proportionality between osmotic pressure, concentration, and
temperature. He revealed that osmotic pressure is proportional to concentration and temperature
and the relationship can be described by the following equation.

π = n2 RT
Where, π = osmotic coefficient
N2 = molar concentration of solute in the
solution R = gas constant
T = Absolute temperature
Osmotic pressure is a colligative property, which depends on the concentration of solute that
contributes to osmotic pressure. Solutions of different concentrations having the same solute and
solvent system exhibit an osmotic pressure proportional to their concentrations. Thus, a constant
osmotic pressure, and thereby a constant influx of water can be achieved by an osmotic delivery
system that results in a constant zero order release rate of the drug. The rate of drug release from
osmotic pump depends on the drug solubility and the osmotic pressure of the core; hence, these
systems are suitable for delivery of drugs with moderate water solubility.

2.0 MATERIAL & METHOD

Ranolazine was obtained as a gift sample from Xylopia laboratory, Ahmedabad, India. Mannitol
and Microcrystalline cellulose were obtained from SDFCL, Mumbai, India.
Magnesium Stearate, Talc, and Dichloro methane were obtained from molychem, Mumbai, India.
Cellulose acetate was obtained from Oxford laboratory. Hydroxypropyl methylcellulose was
obtained from Suvidhinath laboratories, Vadodara, India.
Dibutyl phthalate was obtained from Finar limited, Ahmedabad, India.

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2.1 METHOD
2.1.1 Preparation of tablet core:
Microcrystalline cellulose, the Osmotic agent was weighed according to given in the
table and pass through sieve no.40. To the above bland Ranolazine was added and
passed through sieve no.18. The shifted materials were mixed for 10 minutes.
Magnesium stearate and Talc was added to above mixture. The mixture was mixed
properly and the blend was compressed by tablet punching machine using a punch of
8 diameters.
Serial Ingredient Quantity (mg)
no.
1 Ranolazine 120
2 Mannitol 60
3 MCC 10
4 Magnesium stearate 5
5 Talc 5

2.1.2 For coating

Core tablets were coated by using perforated pan coating equipment. Cellulose acetate
was selected as a semi-permeable membrane, pH-independent polymer. Cellulose
acetate and HPMC were hydrated in dichloromethane by overnight storage and then
mixed it properly. Dibutyl phthalate as plasticiser was added slowly to above solution.
Addition of plasticizer improves the flexibility of coating.

Serial no. Ingredients Weight

1 Cellulose acetate 4 gms
2 HPMC 2 gms
3 Dibutyl phthalate 2 ml
4 Dichloromethane 100 ml
The coating solution was sprayed over a tablet by spray gun till the desired coating was
obtained. The coated tablet was dried at 50◦ C for 1 Hr. to remove the residual of
coating material.

3.0 EVALUATION
3.1 Evaluation of core tablet:
3.1.1 Hardness test:
The hardness of core tablets was measured by Monsanto hardness tester and it was found
5 kg/cm2.
3.1.2 Friability test:
✓ Friability of core tablets was measured by Roche friabilator using 10 tablets.
✓ Equation for friability testing;

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The friability of core tablet according to above equation was found to be 0.81% which
shows similarity to IP standard value.

3.2 Evaluation of coated tablet:

3.2.1 In Vitro Dissolution study:
The dissolution test was performed using a USP XXIII paddle apparatus at 37◦C ± 0.5 ◦C in 900
ml of 0.1N HCl solution with a speed of 50 rpm.5 ml of Samples was withdrawn after 1-hour time
intervals and ranolazine content was measured using UV-Visible spectrophotometer at a
wavelength of 272 nm.

The absorbance of withdrawn samples

Serial Time (hour) Absorbance

no.
1 1 0.055
2 2 0.104
3 3 0.165
4 4 0.241
5 5 0.328
6 6 0.396

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4.0 RESULT:

4.1 CONCLUSION:

5.0 REFERENCE:
1. Syed SM, Farooqui Z, Mohammed M, Dureshahwar K, Farooqui M. Osmotic Drug
Delivery System : An Overview. Int J Pharm Res Allied Sci. 2015;4(3):10-20.
2. On R, Testing D, Pharmaceutical FOR, Forms D. International Journal of Innovative
Pharmaceutical Sciences and Research. 2013;1(206):206-226. doi:10.13040/IJPSR.0975-
8232.5(5).1914-18.
3. D PS, C GM, K PR, P PV. Preparation and Evaluation of Osmotic Controlled Drug Delivery
System of. 1(1):84-93.

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Practical no. 5
AIM: To prepare and evaluate floating DDS – Hydro dynamically
balanced DDS.
1. INTRODUCTION:
Floating tablet is gastro retentive dosage from which increase the retention time of drug in GIT by
floating in gastric fluid. Hydro dynamically balance drug delivery system (HBS) also called
floating drug delivery system .Floating systems having low density systems that have sufficient
buoyancy to float over the gastric contents and remain in the stomach. While the systems float
over the gastric contents, the drug is released slowly at the desired rate, which results in increased
gastric retentive time and reduces fluctuation in plasma drug concentration.

1.1 Based on the Mechanism of Buoyancy FDDS can be classified in to:

1. Single unit floating Dosage System
(a)Effervescent system (Gas-generating system)
(b)Non-effervescent System
2. Multiple Units Floating Dosage System
(a) Non-effervescent System
(b) Effervescent system (Gas-generating system)
3. Raft Forming System

1.2 Advantages:
• Low risk of toxicity
• Improves patient compliance
• Suitable for delivery of drugs with narrow absorption window in small intestine region.
• Drug acting locally in stomach
• Drug which degrade in the colon
• Drug having rapid absorption through GIT

1.3Application of FDDS:
• Sustained drug delivery
• Site specific drug delivery
• Absorption enhancement

2. MATERIALS & METHODS:

Ranolazine was a generous gift sample from (Xylopia Pharma Lab.Ahmedabad, India ), HPMC
K100M (Otto, Chemicals Pvt. Ltd.), sodium bicarbonate (Finar. Ltd. Ahmedabad, India), Lactose
monohydrate(MOLYCHEM Ltd. ,Mumbai, India) talc(MOLYCHEM Ltd. ,Mumbai, India) and
magnesium stearate (Thrien Laboratory ,Ahmedabad, India)
2.1 Preparation of floating tablets of Ranolazine:
Floating tablet of Ranolazine was prepared by direct compression method. All the ingredients were
accurately weighed and mixed properly. The drug and polymer (HPMC K100M) were blended in
mortar followed by the addition of sodium bicarbonate, Lactose, talc and magnesium stearate. The
forces of compression was adjusted so that the hardness of all the prepared tablet ranges 6.5-
7.5kg/cm from finally compressed into tablets using a rotary tablet punching machine (Model Mini
I, Rimek, 10 station, B tooling, 3mm concave punch)

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2.2 Formulation:

Sr.no. Ingredient Quantity(mg/tab) Use

1 Ranolazine 150 API
2 HPMC K100M 150 Polymer
3 Sodium bicarbonate 50 Effervescent agent
4 Lactose 10 Diluents
5 Talc 1%w/w Lubricant
6 Magnesium stearate 2%w/w Glidant

2.3 Evaluation of floating tablet of Ranolazine:

2.3.1 Hardness test: The crushing strength (Kg/cm2) of tablet was determined by using
Monsanto hardness tester.

2.3.2 Friability test: This was determined by weighing 10 tablets after dusting, placing them
in the friabilator (Roche friabilator) and rotating vertically at 25 rpm for 4min. After
revolutions the tablets were dedusted and weighed again the percent friability was calculated
by the formula

%Friability=(Initial weight-Final weight) x 100

Initial weight

2.3.3. Uniformity of weight: 20 tablets were selected at random and weighed individually.
The average weight of each of tablet was calculated. Individual weights of the tablets were
compared with the average weight. Since the tablets weighed mg, I.P specifies that the tablets
pass the test if not more than two of the individual weights deviate from the average weight
by more than 5%.

2.3.4 Thickness and diameter: Five tablets were randomly selected for the determination of
thickness and diameter with the help of vernier calipers Apparatus.

2.3.5 In-vitro buoyancy study: The test was performed using dissolution testing apparatus
USP type-1. The test for all the formulation was carried out in 900 ml 0.1 HCL at basket
rotation of 100 rpm at 37±0.5 0C. The time required for the tablet to rise to the surface of the
dissolution medium and the duration of time tablet constantly floated on the dissolution
medium was noted as floating lag time and total floating time respectively.
2.3.6 Swelling characteristics (Water uptake study): The swelling properties of the tablets
were determined by placing the tablet in dissolution test apparatus in 900 ml of 0.1 N HCl at
37±0.5 0C. The tablets were removed periodically from the dissolution medium after draining
free from water by blotting paper; these were measured for weight gain. Swelling
characteristics were expressed in terms of percentage water uptake (WU %) shows relationship
between swelling index and time.
Initial weight of tablet
SI % = --------------------------------------- × 100
Weight of swollen of tablet

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2.3.7 In-vitro drug dissolution study: Drug release profiles of Ranolazine floating tablet
were determined by using dissolution testing apparatus, USP type- 1(basket type). The test
for all the formulation was carried out in 900 ml 0.1N HCl and phosphate buffer (pH 6.8)
maintained at 37.50C (±0.5 0C) at 100 rpm. Withdrawing 5 ml filtered samples at preselected
intervals up to 12 hrs monitored during the progress of the dissolution. The release rate from
these hydrophilic polymeric matrices were conducted in a medium of changing pH by starting
with 0.1 N HCl solution (pH 1.2) for 2 hrs, then the tablets were immersed into a phosphate
buffer (pH 6.8) for 10 hrs. Absorbance was measured at 272 nm using a UV
spectrophotometer.

3.0 RESULT:
3.1.1 Pre compression parameter of Ranolazine:
Bulk Density(g/ml) 0.27(g/ml)
Tapped Density(g/ml) 0.38(g/ml)
Angle of Repose 41.24
Carr’s Index (%) 27.86%
Hausner’s Ration 1.38

3.1.2. Post compression parameter of Ranolazine:

Evaluation parameter Result
Hardness(kg/cm2) 6±0.5 kg/cm 2
Friability (%) 0.6%
Weight variation(mg) Pass
Floating Lag time(sec) 7sec
Total floating time (hrs.) >12hrs
Swelling index (%) 98.927%

3.1.3 Dissolution study:

Conc( 900*Conc . Amt. of Drug
Time Absorban mcg/ Amt of Drug Release % Drug
Sr No. (hrs) ce ml) Dilution Conc*Dilution Release(mcg/ml) (mg/ml) Release
1
2
3
4
5
6
7
8
9
10
11
12
13
14

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3.2 CONCLUSION:

4.0 REFERENCES:

1 DESIGN AND CHARECTERISATION OF FLOATING TABLETS OF RANOLAZINE.

(2012). INTERNATIONAL RESEARCH JOURNAL OF PHARMACY, (ISSN 2230 –
8407).
2 Raza, A., Bukhari, N. I., Karim, S., Hafiz, M. A., & Hayat, U. (2017). Floating tablets
of minocycline hydrochloride: Formulation, in-vitro evaluation and optimization.
Future Journal of Pharmaceutical Sciences, 3(2), 131–139.
https://doi.org/10.1016/j.fjps.2017.05.001

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Practical No. 6
Aim: Formulation and Evaluation of Mucoadhesive tablet (Buccal
tablet).

1. INTRODUCTION:
Bioadhesive drug delivery formulations were introduced in 1947 when gum tragacanth was mixed
with dental adhesive powder to apply penicillin to the oral mucosa. In recent years delivery of
therapeutic agents via Mucoadhesive drug delivery system has become highly interesting.
Bioadhesive buccal delivery of drugs is one of the alternatives to the oral route of drug
administration, particularly to those drugs that undergo the first-pass effect. Problems
accompanied by the oral route of administration such as extensive metabolism by the liver, drug
degradation in gastrointestinal tract due to the harsh environment can be solved by administering
the drug through the buccal route. Buccal delivery involves the administration of a drug through
the buccal mucosal membrane (the lining of the oral cavity). Buccal drug delivery is the safer
method of drug utilization because drug absorption is terminated in case of toxicity by removing
the dosage form from the buccal cavity. The drug directly reaches to the systemic circulation
through the internal jugular vein and bypasses the drugs from the hepatic first-pass metabolism,
which leads to high bioavailability. The other advantages of buccal drug delivery include low
enzymatic activity, suitable for drugs or excipients that mildly and reversibly damage or irritate
the mucosa, painless drug administration, easy drug withdrawal. A suitable buccal drug delivery
system should be flexible and should possess good bioadhesive properties so that it can be retained
in the oral cavity for the desired duration. In addition, it should release the drug in a controlled and
predictable manner to elicit the required therapeutic response. Various buccal mucosal dosage
forms are suggested for oral delivery which includes: buccal tablets, buccal patches, and buccal
gels.

In this study, buccoadhesive tablets of Ranolazine have been developed using polymer like
Carbopol 934 and non-ionic polymer Hydroxy propyl methyl cellulose K4M (HPMC K4M).
Ranolazine is BCS class 2 drug, which taken as a model drug for buccoadhesive formulation.

2. MATERIALS & METHODS:

2.1. Materials:
Ranolazine is gift sample from Xylopia Laboratory (Ahmedabad, Gujarat, India), HPMC K4M
was purchased from Colorcon Asia Pvt Ltd. (Goa, India), Carbopol 934 was purchased from Corel
pharma (Ahmedabad, India), Mannitol was purchased from Finar Chemicals Limited
(Ahmedabad, India), Mg. Stearate and Talc were purchased from Molychem Ltd. (Mumbai, India).
2.2. Buccoadhesive tablets preparation:
Ranolazine was mixed manually in polybags with different ratios of Methocel K4M (HPMC
K4M) mixture and Carbopol 934 as mucoadhesive polymers and mannitol as diluent (table 1) for 10
mins. The blend was lubricated with magnesium stearate for 3‐5mins and talc was added as a
glidant.

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Flat faced tablet weighing approximately 120 mg were prepared from each mixture. The mixture
powder was placed manually into a stainless-steel die with an inner diameter of 5 mm and
compressed using automated rotary tablet punching machine (Rimek, Model Mini 1, Karnavati
Engineering limited, Kadi, Mehsana, Gujarat, India).

Table 1: Formulation composition of Ranolazine buccal tablets

INGREDIENTS F1 (mg) (1:1.5) F2 (mg) (1:1.75)
Ranolazine 20 20
Carbopol 934 31.25 35
HPMC K4M 31.25 35
Mannitol 34.87 27.3
Mg. stearate (1%) 0.875 0.9
Talc (2%) 1.75 1.8
TOTAL 120 mg 120 mg

2.3. EVALUATION METHOD:

2.3.1. In-vitro dissolution studies:
The USP dissolution test apparatus (apparatus II paddle type) (Model TDT-08L, Electrolab India
Pvt Ltd, Mumbai, India) was used to study the drug release from the tablets. The dissolution
medium was 900 ml of 0.1N HCl buffer pH 1.2. The release was performed at 37 ± 0.5°C, with a
rotation speed of 50 rpm. 5ml samples were withdrawn at predetermined time intervals and
replaced with fresh medium. The samples were filtered through Whatman filter paper and
analyzed after appropriate dilution by UV spectrophotometer (UV-1800, Shimadzu, Kyoto, Japan)
at 272 nm and drug release was determined from the standard curve.
2.3.2. Dissolution Parameters:
Dissolution medium: 900 ml of 0.1 N HCl buffer with pH 1.2
RPM: 50
Temp: 37 ± 0.5°c
Sample volume withdrew: 5ml
sample λ max: 272 nm
2.3.3. Mucoadhesive Strength:
Mucoadhesive×strength was determined by using modified physical balance method. Cellophane paper 120mm
180mm (Chemdyes Corporation, kotharia Naka Chowk, Rajkot, Gujarat, India) was sticked on 100 ml beaker,
and this beaker was placed in 1Ltr beaker which already contained 0.1N HCl of pH 1.2. Tablet was sticked on
the lower side of a left pan of double pan balance using superglue (Cyanoacrylate adhesive), in both pans of the
balance empty beaker was placed and their weight was adjusted, near to the right-sided pan arrangement of
burette were made for dropwise addition of water, as shown. The mucosal and tablet surface was wetted with
few drops of 0.1N HCl and on the left pan tablet, 5 gm weight was placed for 5min. to allow the initial contact
of mucoadhesion. Then dropwise water was added to a beaker of right pan till the detachment of tablet from the
mucous membrane was observed. The weight of water present in right pan beaker was determined, using
following formula;

Mucoadhesive strength = (Wt. of the beaker + Wt. of the water) – Wt. of the empty beaker

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2.3.4. In Vitro Swelling Studies:

The degree of swelling of the mucoadhesive polymer is an important factor affecting adhesion. For
conducting the study, a tablet was weighed and placed in a petri dish containing 5 ml of 0.1 N HCl
buffer pH 1.2 in 90 min at regular intervals of time (10, 20, 40, and 90 min), the tablet was
taken carefully by using filter paper. The swelling index− was calculated using the following formula. ( ) = ×100
Where S.I = swelling index,
Wt = weight of tablet after swollen at time
t Wo= weight of the initial tablet
2.3.5. Weight Variation Test:
Weight variation test was performed on ten tablets using an electronic balance (BL-220H,
Shimadzu Corporation, Kyoto, Japan) and average values were calculated.
2.3.6. Hardness:
Hardness test was conducted for three tablets using Monsanto hardness tester and average values
were calculated in kg/cm2
2.3.7. Thickness:
The thicknesses of buccal tablets were determined using digital Vernier calipers. (Digital Calliper,
Aerospace, India). Ten individual tablets were used and the average thickness was calculated.
2.3.8. Friability:
Friability test was performed on ten tablets using Roche friability tester. Weigh ten tablets and performed friability test,
after that weigh again those ten tablets and calculate friability using following equation;

−1
= ×100
3. RESULT & CONCLUSION:
3.1. RESULT:
3.1.1. In vitro dissolution study:
F1 was found to release 87.62 % of the drug just within 4.5 h whereas F2 released 87.97% of the
drug in 8 hr.

Table 2: Dissolution study for F1

Sr Time Conc. Amount of drug
No. (hrs) Absorbance (mcg/ml) (mg/ml) % Drug release
1
2
3
4
5
6
7
8
9

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Table 3: Dissolution study of F2

Sr. Time Absorbance Conc Dilution Conc* Conc. in Amt of drug % Drug
No. (hr.) (mcg/ml) Dilution 900 ml release Release
(mg/ml)

1
2
3
4
5
6
7
8

3.1.2. In-vitro bioadhesive test:

In vitro bioadhesive test for formulation was performed using modified double pan balance. The
bioadhesive force for F1 and F2 formulation was found as follow;
Table 4: Result of Bioadhesion test
Tablet F1 (gm) F2 (gm)
1.
2.
Avgerage.
3.1.3. Swelling Index:
Swelling index was performed for 90 min. After 90 min swelling index was found as follow;
Initial weight of tablet for F1=125.2mg and F2= 127.7mg

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Time (min) F1 Wt after swelling (mg) F2

10
20
30
40
50
60
70
80
90

% swelling index =

. . .

Fig. 2: Bioadhesion and Swelling index of F1 and F2

3.1.4. Weight variation, hardness and thickness:

All tablets are within the range of weight variation 129.743 and 111.643 mg as per USP. The
thickness of tablets was observed 1.197mm. The mass and thickness of all compressed tablets were
within the limit as per USP. The friability of ten tablets was found to be 0.46. The hardness of all
the tablets was found to be 3.5 kg/cm2.

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Table 6: Physiochemical characteristics of tablet

BATCH HARDNESS THICKNESS SWELLING WEIGHT FRIABILITY
(kg/cm2) (mm) INDEX (%) VARIATION (%)
(mg)
F1
F2

3.2. CONCLUSION:

4. REFERENCES:

1. Vinushitha S. FORMULATION AND IN - VITRO EVALUATION OF BUCCAL

TABLETS OF METOPROLOL TARTRATE. International Journal of Pharmacy and
Pharmaceutical Sciences. 2011;3(2).
2. Choi H, Jung J, Soon C, Rhee C, Lee M, Han J, et al. Formulation and in vivo evaluation
of omeprazole buccal adhesive tablet. Journal of Controlled Release [Internet].
2000;68:405–12. Available from: www.elsevier.com
3. Lakshminarayan S, Nilesh P, Hingawe T. Mucoadhesive buccal tablets of domperidone :
formulation evaluation and effects of process variables. 2013;
4. Shanker G, Kumar CK, Sekhara C, Gonugunta R, Kumar BV, Veerareddy PR. Formulation
and Evaluation of Bioadhesive Buccal Drug Delivery of Tizanidine Hydrochloride Tablets.
2009;10(2):530–9.
5. Akbari J, Saeedi M, Enayatifard R, Sagheb M. Development and Evaluation of
Mucoadhesive Chlorhexidine Tablet Formulations. 2010;9(June):321–7.
6. Jadhav BK, Khandelwal KR, Ketkar AR, Pisal SS. Formulation and Evaluation of
Mucoadhesive Tablets Containing Eugenol for the Treatment of Periodontal Diseases.
2004;30(2):195–203.

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Practical No. 7
Aim:-Formulation and evaluation of transdermal patches
of Ranolazine.

1.0INTRODUCTION
Transdermal drug administration generally refers to the topical application of agents to the healthy
intact skin either for localized treatment of tissues underlying the skin or for systemic therapy. For
transdermal products, the goal of dosage design is to maximize the flux through the skin into the
systemic circulation and simultaneously minimize the retention and metabolism of the drug in the
skin.
Transdermal drug delivery has many advantages over the oral route of administration such as
improving patient compliance in long-term therapy, bypassing the first-pass metabolism, sustaining
drug delivery, maintaining a constant and prolonged drug level in plasma, minimizing inter- and
intrapatient variability, and making it possible to interrupt or terminate treatment when necessary.
Ranolazine is antianginal class of drug and used in the treatment of chronic angina. It has antianginal
and anti-ischemic effects. The mechanism of action of ranolazine is unknown. The in-vitro study
suggests that ranolazine is p-GP inhibitor. It altering the intracellular late-sodium current, thus it
indirectly prevents the calcium overload that causes cardiac ischemia.

2.0MATERIALS & METHODS

2.1 Materials
Ranolazine (API) was received as a gift sample from Xylopia laboratory, Ahmadabad, India. The
polymer is obtained from Molychem, Mumbai, India. .The dibutyl phthalate which is used as a
plasticizer is obtained from Finar limited, Ahmadabad, India. The solvents used in the study that are
isopropyl alcohol and Dichloro methane are obtained from Molychem, Mumbai, India.

2.2 PREPARATION OF TRANSDERMAL FILMS

Solvent casting method

The polymer Eudragit S100 was taken in required quantity as shown in the table. About 20 ml of
a solvent mixture of dichloromethane: isopropyl alcohol (1:1) was added and shaked to prevent the
formation of lumps, and then kept aside for swelling of the polymer. And after complete solubilization
of polymer in a mixture of solvent added required quantity of dibutyl phthalate (plasticizer) to this
mixture, and vortexed. Finally weighed the quantity of Ranolazine added to the polymer solution and
mixed well. It was set - aside for some time to exclude any entrapped air and
2
was then transferred to a previously cleaned Petri plate (70 cm ) and then this was kept aside for

solvent evaporation. The rate of solvent evaporation was controlled by inverting a glass funnel over
the Petri plate. After overnight, the dried films were taken out and stored in a desiccator.

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(Table. No. 1: Formulation of Ranolazine Patches)

Ingredients (in mg or ml) Quantity taken

Ranolazine(API) 20 mg
Eudragit-S100(Polymer) 650mg
Dichloromethane(solvent) 10ml
Isopropyl alcohol(solvent) 10ml
Dibutyl phthalate(plasticizer) (in %w/v of polymer) 30%

(Figure.No:1.MatrixDiffusion–ControlledSystem)

2.3EVALUATION METHOD
2.3.1 Thickness
The thickness of films was measured by digital Vernier calipers. The thickness uniformity was
measured at five different sites and an average of five readings was taken with standard deviation.
2.3.2 Folding endurance:
The folding endurance was measured manually for the prepared films. A strip of film (4x3 cm) was
cut evenly and repeatedly folded at the same place till it broke. The number of times the film could
be folded at the same place without breaking gave the exact value of folding endurance.
2.3.3 Weight variation:
The three disks of 2*2 cm2 were cut and weighed on electronic balance for weight variation test. The
test was done to check the uniformity of weight and thus check the batch- to- batch variation.
2.3.4 Drug content Determination:
2
The prepared drug contained patches specified the surface area (2 cm ) were cut and dissolved in

(5% of methanol contained) 100ml of pH 7.4 phosphate buffer, and vigorously shaked for 12hrs, and
then sonicated for15minutes, centrifuged at 5000 rpm for 30 min. Filter the drug contained polymeric
solution through 42 number Whatman filter paper, then 1ml of the filtrate was taken in a test tube and
dilute it for five times with the same solvent by using double beam UV-Visible

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spectrophotometer to determined drug content at lambda max 272nm. Respected Placebo patch was
taken as a blank solution.

2.3.5 In-vitro drug diffusion study

The drug diffusion studies through dialysis(cellophane) membrane experiments were conducted by
using vertical type diffusion cell (Franz type) having receptor compartment 15ml volume with 2cm
2
area. The receptor compartment was filled with 15ml of phosphate buffer pH 7.4; the activated dialysis
membrane was mounted on the flange of the diffusion cell receptor compartment. The
2
prepared Transdermal patch with surface area 2cm placed on the center of the membrane, the donor

compartment was then placed in position and the two valves of the cell clamped together. The whole
assembly was kept on a magnetic stirrer and solution in the receptor compartment was constantly
o
and continuously stirred using a magnetic bead and at 32 C maintained.

Fig. No. 2:Franz-diffusioncell

3. RESULT :

FORMULATION Weight Thickness Folding Flatness(%) Appearence

variation (µ m) endurance
(mg)
1

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4. CONCLUSION:

5. REFERENCE
(1) Sirisha VNL, Kirankumar P, Chinnaeswaraiah M, College AP, Jntuh A, Pradesh A.
Formulation and Evaluation of Transdermal Patches of Propranolol Hydrochloride
INVESTIGATION OF PHYSICOCHEMICAL COMPATIBILITY OF DRUG
AND. 2012;2(5):31–7.
(2) Sahoo BK, Mishra AK. FORMULATION AND EVALUATION OF
TRANSDERMAL PATCHES. :4965–71.

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Practical No. 8
Aim: To carry out pre-formulation studies of powder & Tablets.

1.0 INTRODUCTION:
Theory of pre-formulation:
Prior to the development of dosage form, the study of certain fundamental physical-chemical
properties of potential drug molecules and other derived properties of drug powder is called as pre-
formulation.
Almost all new drugs are marketed as tablet capsules or both. Only a few drugs are marketed as
an injection. However, the formulation for the intravenous route is always required during early
toxicity, metabolic, bioavailability and clinical studies to provide a precise drug dosing.

Information required in pre-formulation is as…

a. Spectroscopy
b. Solubility
c. Melting point
d. Assay development
e. Stability
f. Microscopy
g. Powder flow, bulk density, angle of repose
h. Compression properties
i. Excipient compatibility.

Spectroscopy:
UV Spectroscopy
The first requirement of any pre-formulation study is the development of a simple analytical
method for quantitative estimation in subsequent steps. Most of the drugs have aromatic rings
and/or double bonds as part of their structure and absorb light in UV range, UV spectroscopy
being a fairly accurate and simple method is a performed estimation technique at early pre-
formulation stages. The absorption Coefficient of the drug can be determined by the formula:
E = AF / X
Where, A = Absorbance
F = dilution factor
X = weight of drug (mg)
It is now possible to determine the concentration of drug in any solution by measuring
absorbance.

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C= AF / E mg/ ml
Characterization of drug molecules is a very important step in the pre-formulation phase
of product development.
Solubility:
Aqueous Solubility
The availability of a drag is always limited and the pre-formulation scientist may only have 50 mg.
Solubility dictates the ease with which formulation for oral gavages and intravenous injection
studies in animals are obtained the pKa allies the informed of pH to maintain solubility and to
choose salts required to achieve good bioavailability from the solid state and improve stability and
powder properties.
Inteinsic Solubility (Co)
An increase in solubility in acid compared to aqueous solubility suggests a weak base and an
increase in alkali, a weak acid. An increase in acidic and alkaline solubility suggest either
impotence or zwitter ion behavior. In this case, there will be two pKa’s, one acidic & one basic.
When the purity of the drug sample can be assured the solubility obtained in acid for a weak acid
or alkali for a weak base can be assured to be the intrinsic solubility (Co.) i.e. the fundamental
solubility when completely unionized. The solubility should ideally be measured at two
temperatures.
1. 4C to ensure physical stability and entered short-term storage and chemical stability unit
more definitive data are available. The minimum density of water occurs at 4C. This leads
to a minimum aqueous solubility.
2. 37 oC to support biopharmaceutical evaluation.
pKa Determination:
Determination of the dissociation content for a drug capable of ionization within a pH range of 1
to 10 is important since solubility and consequently absorption, can be altered by orders of
magnitude with changing pH. The Henderson – Hasseslebach equation provides an estimate of the
ionized and unionized drug concentration at a particular pH.
For acidic compounds
pH = pKa + log (un-ionized drug]) / [ionized drug])

Partition Coefficient:
Partition Coefficient (oil/ water) is a measure of a drug’s lipophilicity and an indication of its ability
to cross cell membranes. It is defined as the ratio of the unionized drug distributed between the
organic and aqueous phases at equilibrium.
P o/w = (C oil / C water) equilibrium.

Dissolution:
The dissolution rate of the drug is only important where it is the rate-limiting step in the absorption
process. Kaplan suggested that provided the solubility of a drug exceeded to mg/ ml at pH, 7 no

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bioavailability or distinction related problems were to be expected. Below / mg/ ml such problems
were quite possible and salt formation could improve absorption and solubility by controlling the
pH of the microenvironment, independently of the drug and dosage forms position within the GI
Tract.
Common Ion Effect: A common ion significantly reduces, the solubility of a slightly soluble
electrolyte. The ‘selling out’ results from the removal of water molecules as solvent owing to the
completing hydration of other ions. The reverse process ‘salting in’ carries with large anions e.g.
benzoate, salivate which open the water structure. These hydro topics increase the solubility
of properly water-soluble compounds such as diazepam.

Melting Point
The melting point of a drug can be measured using three
techniques 1) Capillary Melting 2) Hot Stage Microscopy
3) Differential scanning calorimetry or thermal Analysis.
Polymorphism
A polymorphism is a solid material with at least two different molecular arrangement which give
distinct crystal species. The highest melting species is generally more stable and other
polymorphism is metastable and converts to stable forms.

Particle size determination:

The microscopy has two major application in pharmaceutical pre-formulation. Basic
crystallography, to determine crystal morphology, polymorphism and solvates.
Most pharmaceutical powders have crystals in the range 0.5-300 micrometer, the distribution is
often smaller, typically 0.5-50micrometer to ensure good blend homogeneity and rapid dissolution.
Particle size analysis.
#-small particles are important in low dose.
#-dissolution rate is directly proportional to surface area.
Power Flow Properties:
When limited amounts of drugs are available Power flow properties can be evaluated by
measurements of bulk density and angle of repose. Changes in particles size and shape are
generally very important an increase in crystal size or a more uniform shape will lead to a small
angle of repose and a smaller Carr’s index.
Bulk Density:
Knowledge of absolute and bulk density of the drug substance is Very useful in having some idea
as to the size of the final dosage form the density of solids also of affects their flow Properties
Carr’s compressibility index can be used to predict the flow properties based on density
measurement.

Loose bulk density = wt. of powder/volume of packing

Tapped bulk density= wt. of powder/ tapped volume. Of Packing

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Carr’s index (%) = Tapped density –Poured density *100

Tapped density

A similar index has been defined by Hausner:

Hausner ratio = Tapped density

Pored density

Angle of repose:
The maximum angle which is formed b/w the surface of a pile of powder and the
horizontal surface is called the angle of repose.
Stability
Drug degradation occurs by four main processes…
Hydrolysis
Oxidation
Photolysis
Trace metal catalysis
Whenever possible commercial pharmaceutical product should have a shelf life of 3 year .the
potency should not fall below an acceptable minimum.
Temperature also effect on the stability of the drug.
pH- The degradation of the most drugs is catalyzed by extremes of pH i.e. high H30+ OR OH- and
most drugs have their maximum stability between pH 4to8.
Compatibility
Compression properties and excipient compatibility are used as the pre-formulation
based. For excipient:
The successful formulation of stable and effective solid dosage form depends on careful selection
of the excipient which is added to facilitate administration promote the consistent release and
bioavailability of the drug and protect it from degradation.

2.0 MATERIALS & METHOD

2.1 Materials
Ranolazine, Microcrystalline cellulose, HPMC K 100M, DiCalcium Phosphate, Talc,
Magnesium stearate, HCl, NaOH, KCl, potassium dihydrogen phosphate
2.2 Method:
2.2.1Bulk density
5gm of powder was taken and transferred into measuring cylinder and measured the volume of
powder. The Same procedure was followed by all gave a polymer.
2.2.2Tapped density
Weigh accurately 5 gm of powder &, transferred it to the measuring cylinder. Tapped 100 times
& measured the volume. The Same procedure was followed by all given polymer.
2.2.3Angle of Repose
5 gms of powder was taken. Glass funnel was placed on the stand to a height of approximately 2
cm. The plain paper was placed under the funnel. The powder flowed through the funnel. A static

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heap of powder tended to form a conical mold. The angle of repose from the equation was
calculated from the conical mold.

2.2.4 Particle size distribution

First ranolazine suspension in liquid paraffin was prepared. Microscope with a calibrated slide
was taken. The ocular disc was taken and minimum range to calculate the particle was find out.
A drop of suspension was putted on the slide.100 particles were count and mean was calculated,
the range of sizes was reported as a histogram.
2.2.5 Solubility
10 mg of drug was taken & dissolved in 10 ml buffer solution in 1o ml volumetric flask.the drug
was added until the solution became saturated.solution was sonicated for 15 minutes. The solution
was kept for 24 hr. Then centrifuged and the clear solution was taken and filtered. The solution
was analyzed by UV spectroscopy and solubility was measured. The same procedure was repeated
for different pH solution.
2.2.6 Partition coefficient
300mg of the drug was weighed and it was dissolved in two immiscible solutions (ph1.2 HCl
buffer/Octanol) in separating funnel. The funnel was shacked for some time and kept it until both
layers were separated. Each solution was taken out and measure the solubility by UV
spectroscopy.
2.2.7 pka determination:
A phosphate buffer of various different pH was prepared and absorbance was taken by UV
spectroscopy and the graph was the plot of pH vs abs. Find out pka by dividing maximum
absorbance by 2.

3.0 RESULT:
Table 1
Material Parameters
Bulk Tapped Carr’s index Hausner’s Angle of
density density( (%) ratio repose
(gm/ml) gm/ml (%)
Ranolazine
HPMC K 4M
Magnesium stearate
Talc
MCC
HPMC K 1OO
HPMC K15 M

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Table 2 Particle size distribution

Sr no. Particle size No. Of particle Mean value Cumulative
range Fi Xi frequency fixi
1
2
3
4
∑fixi

Factor: 7 division of eyepiece =110µm of stage micrometer

1 division of eyepiece =?
110×1/7=15.71µm n =no of particles Average particle size =
∑fixi/n

=224/100
=2.24
Particle size= average × factor=2.24*15.71=35.1904µm

Table 3 solubility at different pH buffer

pH Absorbance Solubility(mg/ml)
1.2-hydrochloric buffer
2- hydrochloric buffer
7- phosphate buffer
7.4-phosphate buffer
8- phosphate buffer

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Figure 1.Graph for solubility vs different pH of buffer solution

Partition coefficient (log P) = -1.39(less than 1, so the drug was found hydrophilic in nature)
Pka value=1.2

3.1 CONCLUSION:

4.0 REFERENCES
1. White JA, Haghighi C, Brunner J, Estrada M, Lal M, Chen D. Preformulation studies
with the Escherichia coli double mutant heat-labile toxin adjuvant for use in an oral
vaccine. J Immunol Methods. 2017;(September):0-1. doi:10.1016/j.jim.2017.09.003.

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Practical No. 9
Aim: To study the effect of compressional force on tablets
disintegration time.

1.0 INTRODUCTION:
In oral tablet dosage form there are several factors like hardness and applied compressional force
shows a major effect on tablet disintegration time and drug release profile. Generally, increase in
hardness and applied compressional force shows increase in disintegration time and delay in drug
release from the dosage form. The purpose of this experiment is to determine the effect of different
diluents compressed maintaining same hardness and effect of different compressional forces (i.e.
0.5, 1, 1.5, 2, 2.5, 3.0 tons) on disintegration time of tablet formulation.

2.0 MATERIALS & METHODS:

2.1 Materials
Calcium phosphate dibasic (Chemdyes Corporation, Navrangpura, Ahmedabad, India),
Microcrystalline cellulose (MOLYCHEM LTD., Mumbai, India), Lactose monohydrate (S D fine-
chem Limited, Worli Road, Mumbai, India), Mannitol (S D fine-chem Limited, Worli Road,
Mumbai, India), Sodium carboxy methyl cellulose (Wilson Laboratories, Bombay, India), HPMC
15 CPS (Colorcon Asia PVT LTD, Goa, India), Talc (MOLYCHEM LTD., Mumbai, India),
Magnesium stearate (Thrien Laboratory, Ahmedabad, India).
2.2 Methods
2.2.1 Tablet preparation
For first method flat-faced tablet weighing approximately 202 mg were prepared from each mixture.
The mixture powder was placed manually into a stainless steel die with an inner diameter of 8 mm and
compressed at 3.5 kg/cm2 force on an automated rotary tablet punching machine (Punch No. 5, Rimek
Model MINI 1 (10 Station) Karnavati Engineering LTD), Nani kadi, Taluka
–KADI, Dist. Mehsana, North Gujarat, India). The hardness of tablet was measured using Pfizer
& Monsanto hardness tester.
For Second method flat-faced tablet weighing approximately 602 mg were prepared from a
mixture. The mixture powder was placed manually into a stainless steel die with an inner diameter
of 13 mm and compressed at 0.5, 1.0, 1.5, 2.0, 2.5, 3.0 tons compressional force on a KBr Hand
press (Model: SSP-10A, Shimadzu, Kyoto, Japan).
2.2.2 Materials
Ten Grams of mixture of each formulation consisting of Diluents (89%w/w), Sodium
carboxymethyl cellulose (5%w/w), HPMC 15 CPS (4%w/w), Talc (2%w/w), & Magnesium
Stearate (1%w/w) were mixed in mortar-pestle

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Table 1. The formula for a tablet containing Different Diluents.

Ingredients FD1 FD2 FD3 FD4 Quantity
Diluent Micro Calcium Mannitol Lactose 180 mg
crystalline phosphate di monohydrate
cellulose basic
Disintegrant Na CMC Na CMC Na CMC Na CMC 9 mg
Binder HPMC15 HPMC 15 HPMC 15 HPMC 15 CPS 7.2 mg
CPS CPS CPS
Glident Talc Talc Talc Talc 3.92 mg
Lubricant Mg Mg Stearate Mg Stearate Mg 1.96 mg
Stearate Stearate
Total Weight 202.08 mg

Table 2a. Formula for Tablets Compressed at Various compressional Forces.

Ingredients Type Ingredients Name Quantity
Diluent Micro crystalline cellulose 543 mg
Disintegrant Na CMC 27 mg
Binder HPMC 15 CPS 16 mg
Glident Talc 11 mg
Lubricant Mg Stearate 5.31 mg
Total Weight 602.31 mg

Table 2b. Weight variation of Tablets Compressed at Various Compressional forces.

Formulation Applied Pressure Tablet Weight (mg)
F1 0.5 tons 600
F2 1.0 tons 610
F3 1.5 tons 598
F4 2.0 tons 608
F5 2.5 tons 605
F6 3.0 tons 603

2.2.3 Evaluation
Hardness is measured using Monsanto & Pfizer (Cadmach) hardness tester in kg/cm2. To maintain
uniform hardness in all 4 formulations.
Tablet disintegration time was measured in the USP tablet disintegration apparatus (Electrolab India
PVT. LTD. Model: ED-3PO, Goregaon East, Mumbai, India) in 37 ± 1º C water. Disintegration testing
was performed without disks to avoid obscuring the differences in times between tablets compressed
at the various forces. When disks are used, the disintegration time always shows an increasing trend
starting from the lowest compressing force in all experiments. The mechanical action exerted by the
disks apparently aids the disintegrating tablet to break up into smaller pieces which are even more
susceptible to breakage by mechanical force. Use of disks

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thus seems to result in disintegration times that reflect the mechanical strength of the tablets, as do
hardness values.
3. RESULT & DISCUSSION
3.1 RESULT
Table 3. Disintegration time for tablets containing Different Diluents.
Sr. no
Diluent Disintegration time
1
2
3
4

Hardness of tablets containing Different Diluents.: 3.5 kg/cm2 (For each formulation)
Disintegration times are shown in a bar chart (Fig. 1) of four tablets. Tablets containing Calcium
phosphate dibasic (FD2) as diluent had shorter disintegration time and Mannitol (FD3) had longer
disintegration time as compare to other diluents used in the formulation.

Figure 1. Graph of Disintegration time v/s Formulation containing Different Diluents.

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Table 4. Disintegration time for Tablets Compressed at Various compressional Forces.

Sr.
1 no Formulation Disintegration time
2
3
4
5
6

Disintegration times are shown in a bar chart (Fig. 2) of six tablets. Tablets compressed at the
lower forces had shorter disintegration time and at the higher forces had longer disintegration time
up-to 2.5 tons compressional force. Then after there is no significant difference is observed on
disintegration time with an increase in compressional force.

Disintegration time vs Formulation

194 210 200

Figure 2. Graph of Disintegration time v/s Formulation of tablets Compressed at Various

compressional Forces.

3.2. CONCLUSION:

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4. REFERENCES
1. Shipar MAH, Ashish W, Cherian V NK, and NT. Effect of Compression Force on Tablet
hardness and disintegration time. 2014;(1):4-15.
2. Marais AF, Song M, De Villiers MM. Effect of compression force, humidity and
disintegrant concentration on the disintegration and dissolution of directly compressed
furosemide tablets using croscarmellose sodium as a disintegrant. Trop J Pharm Res.
2003;2(1):125-135. doi:10.4314/tjpr.v2i1.14577.
3. Khan KA, Rhodes CT. Effect of variation in compaction force on properties of six direct
compression tablet formulations. J Pharm Sci. 1976;65(12):1835-1837.
doi:10.1002/jps.2600651235.

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Practical No. 10
AIM: Effect of three binders on the dissolution rate of
ranolazine tablets.

1.0 INTRODUCTION
Ranolazine is a piperazine derivative is a new anti-ischemic drug for the treatment of angina.
Ranolazine is to inhibit late in a thus preventing sodium overload of the cell. As a consequence,
ranolazine prevents reverse mode sodium–calcium exchange and thus diastolic accumulation of
calcium possibly resulting in improved diastolic tone and improved coronary blood flow.
Ranolazine tablet evaluate the effect of three used binders on three binders namely (PVP K30),
HPMC, HPMC K100, the tablets were evaluated for various tablet parameters including
dissolution rate to evaluate the effect of binders.

2.0 MATERIAL & METHODS

MATERIAL
Ranolazine, PVP K 30, HPMC, HPMC K 100, lactose, talc, Mg. stearate.
Ranolazine tablets were prepared by wet granulation method. All the tablets prepared were
evaluated for hardness, friability, disintegration time and dissolution rate as per official methods.
All the ranolazine tablets prepared using various binders disintegrated within 2 min. The order of
increasing. PVP K30 > HPMC>HPMC K100
2.1 Methods
2.1.1 Estimation of Ranolazine:
An UV Spectrophotometric method based on the measurement of absorbance at 272nm in
phosphate buffer of pH 6.8 was used for the estimation of Ranolozine. The method was validated
for linearity, accuracy, precision and interference.

2.1.3 Preparation of Ranolazine Tablets:

Ranolozine (100 mg) tablets were prepared by wet granulation method as per the formula given in
Table 1 using three different binders. The required quantities of Ranolozine, lactose and binder as per
the formula in each case were blended thoroughly in a dry mortar and granulated with ethyl alcohol
(q.s.) as granulating fluid. The wet mass formed was pressed through mesh no.12to obtain wet granules.
The wet granules were dried at for 1hour. The dried granules were passed through mesh no.14 to break
the aggregates formed and to obtain discrete granules. Super disintegrant, talc and magnesium stearate
were passed through mesh no.80 and collected on to the bed of tablet granulations prepared and mixed.
The tablet granules were blended thoroughly in a closed bag and compressed in to 200 mg tablets using
an 8- station RIMEK tablet punching machine.

2.2Evaluation of Tablets:
Ranolazine tablets prepared were evaluated for , hardness, friability, disintegration time and
dissolution rate as per official methods.
2.2.1Hardness:
➢ The hardness of prepared tablets was determined by using Monsanto hardness tester and
measured in terms of kg/cm2.

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2.2.2Friability:
➢ The friability of the tablets was measured in a Roche friabilator using the
formula. Friability:

2.2.3 Disintegration time:

Disintegration time of the tablets was determined using single unit disintegration test apparatus
using phosphate buffer 6.8.

2.2.4 Dissolution Study:

Dissolution rate of Ranolozine tablets prepared was studied in phosphate buffer of pH 6.8(900 ml)
employing eight station dissolution rate test apparatus using paddle stirrer at 50 rpm and at a
temperature of 37°C ± 1°C. One tablet was used in each test. Samples of dissolution fluid (5 ml)
were withdrawn through a filter at different time intervals and assayed for Ranolozine at 272 nm.
The sample of dissolution fluid withdrawn at each time was replaced with fresh drug free
dissolution fluid and a suitable correction was made for the amount of drug present in the samples
withdrawn.

Table 1: Formulae of Ranolazine Tablets Prepared Employing Various Binders

Ingredient (mg/ tablet)
Ingredient F1 F2 F3
Ranolazine 100mg 100mg 100
PVP K 30 4 mg
HPMC 30mg
HPMC K100 50
MCC pH101 22
Lactose 3mg 66
Talc 1mg 1.5 1
Mg. stearate 2mg 2.5 2

Table 2: Physical Parameters of Ranolazine Tablets Prepared

Formulation hardness Friability% Disintegration
F1 4.5 1.02 15 min
F2 4.4 1.7 48 min
F3 6.8 0.72 38 min

3 RESULTS & DISCUSSION

➢ The objective of the present study is to evaluate the effect of three commonly used binders on the
dissolution rate of Ranolazine tablets. Tablets each containing 100 mg of Ranolazine were

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formulated employing three commonly used binders namely (PVP K30), (HPMC k100).
(HPMC) comparison purpose all the binders were used at the same strength, 6.5% w/v in the
formula. The tablets were prepared by wet granulation method as per the formulae given in
Table 1.
➢ All the tablets prepared were evaluated for drug hardness, friability and disintegration time
and dissolution rate as per official methods. The physical parameters of the Ranolazine tablets
prepared are given in Table 2. The hardness of the tablets was in the range 4.5-5.0 kg/cm2.
Weight loss in the friability test was less than 1 % in all the cases. Ranolazine content of the
tablets prepared was within 100±3 %.
➢ Dissolution rate of Ranolozine from the tablets prepared was studied in phosphate buffer of
pH 6.8.
➢ The dissolution profiles of Ranolozine tablet prepared employing various binders are shown
in table.
➢ The dissolution parameters are summarized in Table. Though all the binders were used at the
same strength of 6.5% w/w difference were observed in the dissolution parameters of tablets
prepared. The binder used has significantly influenced the dissolution rate of Ranolozine
tablets prepared. The order of increasing dissolution rate (K1) observed with various binders
was PVP K30> HPMC K100 >HPMC.

Table 3: Dissolution Parameters of Ranolazine Tablets Prepared Employing Various

Binders HPMC K100
Sr Time Absorbance Conc Dilution Conc* Amt of Drug Amt. of % Drug
No. (hrs) (mcg/ml) Dilution Release Drug Release
(mcg/ml) Release
(mg/ml)
1
2
3
4
5
6
7
8
9
10
11
12

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PVP K30
Sr Time Absorbance Conc Dilution Conc* Amt of Amt. of % Drug
No. (hrs) (mcg/ml) Dilution Drug Drug Release
Release Release
(mcg/ml) (mg/ml)
1
2
3
4
5
6
7
8
9
10
11
12
13

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HPMC
sr no. Time (hrs.) absorbance conc(mcg/ml) amt. of drug(mg/ml) %drug release
1
2
3
4
5
6

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3.1 CONCLUSIONS

4.0 REFERENCE
1. Lachman. L., Liberman, M.A. and Kanig, J.L.,Eds., in: The Theory and Practice of
Industrial Pharmacy, 2ndEdn. Lea andFebiger, Philadelphia, 1978;328.
2. Chowdary, K.P.R., and Aparajitha, N.,The Eastern Pharmacist., 1989; 32:121.
3. Chowdary, K.P.R., and Manjula, T., Indian J. Pharm. Sci., 2000; 62: 224.
4. S. Jaya, K.P.R. Chowdary, P. Rajeswara Rao.,Int. Res J Pharm. App
Sci.,2012; 2(4):109 -113.
5. Chowdary, K. P. R., Lingaraju S Danki and Hiremath, S. N., Der Pharmacia Lettre.,
2010;2(2): 221-236.

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Practical No. 11
AIM: To plot Heckel plot, Higuchi and Peppas plot and determine
similarity factor.

1. INTRODUCTION
1.1. HECKEL PLOT:
In 1961 Heckel postulated a linear relationship between the relative porosity (inverse density) of
a powder and the applied pressure. The slope of the linear regression is the Heckel constant, a
material dependent parameter inversely proportional to the mean yield pressure (the minimum
pressure required to cause deformation of the material undergoing compression). Large values of
the Heckel constant indicate susceptibility to plastic deformation at low pressures when the tablet
strength depends on the particle size of the original powder. The intercept of the line indicates the
degree of densification by particle rearrangement.
The Heckel equations
Heckel (1961a) developed his equation by assuming similarity to a first-order chemical reaction,
where the concentration is substituted with porosity and the time with pressure.
dD /dP = K*(1−D)
Where P is the pressure, D the relative density of the compact and K is a constant. Eq. assumes
that the rate of change in density with respect to pressure is directly proportional to the remaining
porosity.
The Heckel transformation is practically linear at low of fit at low pressures. At high densities, the
Heckle transformation tends to infinity. This means that the heckle plot will show an upward
curvature near zero porosity.
1.2. HIGUCHI PLOT:
Higuchi in 1961 and in 1963 developed models to study the release of water-soluble and low
soluble drugs incorporated in semisolid and solid matrices. To study the dissolution of a planer
system having a homogeneous matrix the relation obtained is shown in the equation.

Q = [ D ( 2C-CS) CS t ]1/2
Where Q is the amount of drug released in time t per unit area, C is the initial drug concentration,
Cs is the drug solubility in the matrix media and D is the diffusivity of drug molecules in the matrix
substance.

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1.3. PEPPAS PLOT:

Korsmeyer and Peppas in 1984 developed an empirical equation to analyze both Fickian and non-
Fickian release of drug from swelling as well as non-swelling polymeric delivery systems. The
equation is represented as from a planer system having a homogeneous matrix the relation obtained
is shown in equation
∝ Mt/M = Ktn

Where Mt/M is a fraction of drug released at time t, n is diffusion exponent indicative of the
mechanism of transport of drug through the polymer, K is kinetic constant incorporating structural
and geometric characteristics of the delivery system.
1.4. SIMILARITY FACTOR (F2):
Among several methods investigated for dissolution profile comparison, f2 is the simplest. Moore
and Flanner proposed a model-independent mathematical approach to compare the dissolution
profile using two factors, f1 and f2.

Where Rt is dissolution value of reference batch at time t, Tt is dissolution value of test batch at
time t, n number of observation.f2 value for test sample exists 50 to 100.
2.0 MATERIALS & METHODS
2.1. Materials
Ranolazine (Xylopia Pharma Lab., Ahmedabad, India ), Calcium phosphate dibasic (Chemdyes
Corporation, Navrangpura, Ahmedabad, India) HPMCK4M, HPMCK15M, HPMCK100M) (Otto,
Chemicals Pvt. Ltd.), HPMC 15 CPS (Colorcon Asia PVT LTD, Goa, India), Microcrystalline
cellulose (MOLYCHEM LTD., Mumbai, India), Lactose monohydrate (S D fine-chem Limited,
Worli Road, Mumbai, India), Sodium carboxy methyl cellulose (Wilson Laboratories, Bombay,
India), Magnesium stearate (Thrien Laboratory, Ahmedabad, India), Talc(MOLYCHEM LTD.,
Mumbai, India).
2.1.1. For Heckel plot
2.1.1.1. Mixture composition & Methods
10 grams of lactose monohydrate, Sodium carboxymethyl cellulose, HPMC 15 CPS, Talc, &
Magnesium stearate.
2.1.1.2. Tablet preparation
For first method flat-faced tablet weighing approximately 202 mg were prepared. The mixture powder
was placed manually into a stainless steel die with inner diameter of 8mm and compressed

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at different compressional pressure (3.5, 4.5, 6, 8 kg/cm2) on an automated rotary tablet punching
machine(Punch No. 5, Rimek Model MINI 1 (10 Station) Karnavati Engineering LTD), Nani Kadi,
Taluka –Kadi, Dist. Mehsana, North Gujarat, India). The hardness of tablet was measured using
Pfizer & Monsanto hardness tester.
Table: 1. Formulation of the tablet
Ingredient Quantity
Diluent Lactose monohydrate 180mg
Disintegrant Na CMC 9mg
Binder HPMC 15 CPS 7.2mg
Glident Talc 3.92mg
Lubricant Mg Stearate 1.96mg
Total weight 202.08mg

2.1.2. For Higuchi & Peppas plot & similarity factor:

2.1.2.1. Tablet preparation:
Matrix tablets of Ranolazine with other excipients were prepared by direct compression. The weight
of Ranolazine was kept constant in all the prepared tablets at 100mg/tablet. Different viscosity grades
of HPMC namely HPMC K100M were chosen as polymeric matrix materials. Microcrystalline
cellulose (MCC) was selected as tablet diluent for increasing the compressibility and flowability of the
ingredients as well as to maintain the tablets at a constant weight of 120 mg. Magnesium stearate was
used as a lubricant at a concentration of 2% by weight of the tablet. To make powder mixtures, the
drug, polymer, and MCC were thoroughly mixed for 30 min by means of pestle and mortar. This
powder mixture was then lubricated with magnesium stearate then compressed into tablets in 6 mm
rotary tablet punching machine. The force of compression was adjusted so that hardness of all the
prepared tablets ranges from 5.5-6.5 kg/cm. The detailed compositions of the prepared matrix tablets
formulations are given in below table.
Table: 2.The Formula for Preparation of Matrix Tablet of Ranolazine
Ingredients(mg/tab) Quality
Ranolazine 100
HPMC K100M
Micro Crystalline Cellulose PH101 22
Magnesium Stearate 2%
Talc 1%

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2.2. EVALUATION:
2.2.1. For Heckel plot
Plot the graph ln (1/1-D) vs. applied pressure
Where D = relative density
1-D = Porosity
Relative density =

Where, tablet volume = πr2h r

= Radius of tablet
h= height of tablet
1 kg/cm2 = 98.07 kPa
Lactose monohydrate true density = 1.545 g/cm3

Table: 3. Tablet volume & density data at different hardness

Hardness (kg/cm2) Height of tablet Tablet volume Density of tablet

(mm) (mm3) (g/ cm3)
3.5 2.30 115.552 1.74
4.5 2.23 112.035 1.80
6 2.16 108.518 1.87
8 104.45
2.08 1.94

2.2.1.1. Hardness

The crushing strength (kg/cm2) of the tablet was determined by using Monsanto hardness tester.
2.2.1.2. Thickness and diameter
Five tablets randomly selected for the determination of thickness and diameter with the help of
Vernier caliper apparatus.
2.2.2. For Higuchi plot
2.2.2.1. Determination of swelling behavior:
The swelling-eroding behavior of matrix tablets was determined using the method described by
40Al-Taani and Tashoush. One matrix tablet was weighed and placed in a dissolution apparatus.
The swollen weights of tablets were calculated after placing the mixture in a vacuum oven at
C for 48 h. The following formula was used for calculating %
swelling: % Swelling = ∗100

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Where S is the weight of the matrix after swelling

Plot the graph % drug release vs time
2.2.3. For peppas plot
Plot the graph log % cumulative drug release vs log time

3. RESULT & DISCUSSION:

Table: 4. For Heckel plot:
PRESSURE (kPa) DENSITY OF RELATIVE LN (1/1-D)
TABLET DENSITY D= RD

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Table: 5. Higuchi plot (For Sustain release formulation):

TIME (Hrs.) % DRUG RELEASE
0
1
2
3
4
5
6
7
8
9
10
11
12
23
24

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Table: 6. Peppas plot

Time (hrs.) % drug release Log time Log % cumulative
drug release
0
1
2
3
4
5
6
7
8
9
10
11
12
23
24

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Table: 7. Similarity factor

Time (hrs.) Lab. Marketed
0
1
2
3
4
5
6
7
8
9
10
11
12
23

Fig. 4. Comparison of % drug release of marketed and formulated tablet

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Table: 8. Data for similarity and dissimilarity factor

Time (hrs.) Lab (Tt) Marketed (Rt) Rt- Tt Rt-Tt sq.
0
1
2
3
4
5
6
7
8
9
10
11
12
23
24
Total

. ×
= {+ ( − ) }
F2= 31.005

= ∑ ∑| | −| |×
F1=28.50

3.1 DISCUSSION:
For Heckel plot
This formulation follows the first order kinetics. Here the pressure was increased in this
formulation the porosity was respectively decreased. Porosity basically dependent on the thickness
of the tablet. The thickness of the tablet increase it was directly proportional to the volume and
increase the tablet volume and relative density of this formulation was increased.

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For Similarity factor

This formulation is not comply with the marketed formulation because the similarity factor (f2)
value is 31.005. If this value obtain above 50% than we can say the formulation is comply with the
marketed formulation.

4.0 REFERENCES:
1. Ramteke KH, Dighe PA, Kharat AR, and Patil S V, “Review Article Mathematical Models
of Drug Dissolution : A Review.” 2014, 3, 388–396.
2. Heckel RW, “Density-Pressure Relationships in Powder Compaction.” 1960,.
3. Pharm A, “A Compressibility and Compactibility Study of Real Tableting Mixtures : The
Effect of Granule Particle Size.” 2012, 62, 325–340.
4. Vromans H, Boer AHDE, Bolhuis GK, Lerk CF, Kussendrager KD, and Bosch H, “Studies on
Tableting Properties O F Lactose Part 2. Consolidation and Compaction of Different
Types of Crystalline Lactose.” 1985,.

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