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Pharmatechnology lab journal pharmacy 9th semester
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0% found this document useful (0 votes)
50 views32 pagesRaihab Pharmtech Manual
Pharmatechnology lab journal pharmacy 9th semester
Uploaded by
Erum JanCopyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PDF or read online on Scribd
Introduction to Granulation
|[Gfaiutation is a process of enlargement of powdered particles to form grain-like agglomerates.
In the pharmaceutical industry, the granules formed from the particles of the active
pharmaceutical ingredient (API) and excipient mix are further processed effectively into solid
(dosage forms, such as tabletsjandeapsules, orfmiult particulates. These granules offer the
aulvantages of favourable size distribution, improved bulk density, and flow properties that
further prevent the problems of eaking, segregation, and poor tableting performance,in the
downstream processing. It also of a formulation, by providing
intimate contact between mar
Methods of Granulation:
‘There are majorly two types of methods adopted for granulation
+ Dry Granulation
Wet Granulation
Dry Granulation
In dry granulation method, the primary powder particles are aggregated at high pressure! The
‘two main processes in this method are:
> Slugging
> Roller compaction
Slugging
using a tablet press or, more usually, a large heavy-duty) . The resultant compact is
then filled using a hammer milVor other conventional milling equipment. The milled slugs are
passed through a screen of desired mesh for sizing! Lubricant is added/in the usual manner, and
the granules compressed into tablets.
Roller compaction
Roller compaction (also referred to as fibbon blending) is a relatively simple, more efficient
and inexpensive form of dry granulation. It is a process where formulation ingredients are
continuously passed between two counter-rotating rollers where its densified and consolideted
{nto sheet of solid mass. Lubricant
Screen
Wet Granulation
Wet granulation method is a process of size enlargementyin which fine powder particles are
agglomerated or brought together into larger, strong and relatively permanent structure called
granules Using a suitable hon-ioxe grantlating uid sueh as water isopropanol oF ethanol or
mixtures thereof), The granulating fluid can be used alone or as a solvent containing bit
granulating agent. The chi
ce of the granulating fluid depends greatly on the properties of the
materials to be granulated. Powder mixing, in conjunction with the cohesive properties of the,
+ granulating agenty enables the formation of granules. The characteristics and performance of
the final product, greatly depends on the extent to which the powder particles interact with each
other to form aggregates (granules).
+ Weighing
+ Sieving
+ PreMixing
. Binder solu
n preparation . Kneading/Addition of binder
. Sieving of wet Mass
+ Drying of wet mass
+ Sieving of dried mas
Difference between wet and dry Granulation
‘The two main methods of granulation employed in the pharmaceutical industry for preparing
solid dosage form include wet granulation and dry granulation, The major difference between
these two is the use of bindet. A binder is often added to the formulation to facilitate the wet
‘granulation process. Ideally, a cohesive network between the formulation ingredients is created
by the binder in order to produce granules and tablets that meet the predetermined quality target
(e.g. in terms of granule size distribution, granule friability, tablet tensile strength, and tablet
content uniformity) EXPERIMENT NO 01
Preparation of Granules by Wet granulation using Water as
Binder
Introduction to Binder
|A binder or binding agent is any material or substance that holds or draws other materials,
together to form a eohesive whole mechanically, chemically, by adhesion or cohesion.
Ina more narrow sense, binders are liquid or dough-like substances that harden by a chemical
or psa process and bin bers filler powder and oer parle aed noi)
Examples include glue, adhesive and thickening.
Mechanism
During compression fine particles of power (both active and inactive ingredient) or granules
[must have two properties;
4. Firstly, Proper Flow property: Fine particles have fewer flow properties and thus, they make
problems such as weight variation, segregation of powder particles during manufacturing.
‘2. Secondly, Proper Compressibility: Particles of powder or granules of the tablet should have
proper compressibility.
Compressibility is required for the proper compress of tablets.
‘A binder can accumulate fine particles to large particles (granules) and these large particles
hhave adequate flow properties and compressibility? Certainly, during compression particles
need to compact and this is possible when one or more binders used in a formulation. Thus, a
binder is added either dry or in liquid form during wet granulation to form granules or to
promote cohesive compacts for directly compressed tablets. In addition, the binder ensures the,
Zldcl prOpEHTEs of tablet de ae cee
added either
I. Physiologically inert.
Ay 06 woah
Acceptable to regulatory agencies. Viguid doen
Physiologically and chemically stable. dative, wel grenesh
Should not interfere with the bioavailability of the drug.
Commercially available in a stable form.
Meet the standards of regulatory requirements.
pave epy
Able to cohesive compacts for directly compressed tablets. The @oininioN pharmaceutical Dinders\are sugars (c.gmaltodextring), siatural polymers (c.
staeb), (semi) synthetie polymers (eg. polyvinyl pyotidone (PVP), and eelulose base
polymers (e.g. hydroxypropyl methyl cellulose (HPMC))
Apparatus:
Weighing balance, ‘Tray, Beaker (100ml), Stier, Sieve (mesh no.10), Spatula, Tray dryer,
Measuring eylinder.
Material Required:
Paracetamol powder (APD), Water (Binder), Lactose (Diluent), Starch (Disintegrant), ‘Tale
Weight per
Ingredients | Yrange | %selected | tablet Weight per 25 tablets
250/500mg
APL PCM 500mg, 250mg 6.258 ~
Disintegrant | Starch 2t010% | 5% 25mg, 0.625g
Binder Water 10% 50mg 125g
Glidant | Tale Tio 10% | 1% mg 0.1258,
‘Magnesium
Lubricant 2 11010% | 1% mg 0.1258
stearate
Lactose
Diluent | (quantity 39.5mg | 140mg 3.5¢
sufficient)
Procedure:
— | weighed all the ingredients carefully.
— Then I mixed the weighed lactose, starch and API and spread this mixture on a tray to form a
bed of powder.
= I then gradually added the water as binder in portions using measuring cylinder and mixed
vigorously with the help of hand till the formation of a cracking ball.
— Then I passed this ball through the'sieve of mesh no.10 to produce the granules.
— I put the tray with wet granules in the [ray dryer for drying for 45 minutes'at a temperature 6} Result:
‘The Batch 1 of granules is ready to study the characteristics of granules and tabletting.
* Studs) diferente, blo bode, Med, guider Moree Go van,
“CE8an than anedtion
fe Name amy Other 3 tediicte ure mm puns G EXPERIMENT NO 02
Preparation of Granules by Wet granulation using Starch
mucilage as a Binder
Apparatus:
Multifimetional R & D machine, Weighing balance, ‘Tray, Beaker (100ml), Stirrer, Sieve (mesh
10.10), Spatula, ‘Tray dryer or drying oven, Measuring cylinder,
Material Required:
Paracetamol powder (API), Starch mucilage (Bitidér), Lactose (Diltient), Starch (Disintegraht),
Tale (Glidant),
[ Weight per
Ingredients | Yorange | %selected | tablet Weight per 25 tablets
250/500mg,
‘API PCM 500mg | 250mg 6.258,
Disimtegrant | Starch 21010% [5% 25mg 0.625g
Starch,
Binder muecilage | 510 25% | 10% 50mg, 125g
(7%) _
Glidant Tale 10.10% | 1% Smg 0.1258
Lubricant | M2" Tso 10% | 1% sg 0.1258
Stearate
Lactose
Diluent (quantity 39.5mg 140mg 3.58
sufficient)
Preparation of Binder:
| dispersed/7 gm starch jn a beaker and added distilled water (1Oml) init to make athick’sturry?
Procedure:
I weighed all the ingredients carefully.
‘Then I mixed the weighed lactose, starch and API and spread this mixture on a tray to form a
bed of powder.
I then gradually added the starch mucilage as binder in portions using measuring cylinder and
mixed vigorously with the help of hand till the formation of a cracking ball. ‘Then I passed this ball through the sieve of mesh Ho.10to produce the granules.
| put the tray with wet granules in the Tray dryer for drying for 45 minuféSlatia temperature ol
usin
‘Afler'45 minutes, Took out the dried granules.,
Result:
“The Batch 2 of granules is ready to study the characteristies of gramules and tabletting EXPERMENT NO 3
Preparation of Granules by Wet granulation using Sucrose
50°%w/y as a Binder
Apparatus:
Multifunctional R & D machine, weighing balance, Tray, Beaker (100ml), Measuring Mask
(LOO), Stirver, Sieve (meshno.10), Spatula, Tray dryer or drying oven, Measuring cylinder
Material Required:
Paracetamol powder (API), Sucrose SO%w/y (Binder), Lactose (iltien), Starch
‘Wisintegrant), Tale (Glidand
Weight per wy
Ingredients | Yrange | Yselected | tablet Weight per 25 tablets
250/500mg
API PCM 300mg | 250mg (| 6.258
Disintegrant | Starch 2t0 10% | 5% 25mg 0.625
Binder Sucrose | 1010 70% | 10% somg 125g
Glidant Tale 1 to 10% 1% Smg 0.125g
Lubricant Magi estan 1 to 10% 1% Smg 0.125g¢
Stearate
Lactose
Diluent (quantity 39.5mg, 140mg, 35g
sufficient)
Preparation of Binder:
1 added 50’gm. OF 6oaise sucrose in a flask. Then | added distilled water'in it up to the"/Smi)
mark with continuous stirring and dissolved the sucrose completely with the help of stirrer,
After that I added more distilled water tolmake the Volume up to 100mL/and mixed thoroughly.
Procedure:
1 weighed all the ingredients carefully.
‘Then I mixed the weighed lactose, starch and API and spread this mixture on a tray to form a
bed of powder.
I then gradually added the prepared sucrose S0%w/v as binder in portions using measuring
cylinder and mixed vigorously with the help of hand till the formation of a cracking ball.
‘Then { passed this ball through the sieve ofimesh no.10 to produce the granules. | put the tray with wet granules in the Tray dryer for drying for 45 minutes
After 45 minutes, I took out the tray with dried granules.
Result:
1 Batch 3 is ready to study characteristics of granules and tableting. Objective: Particle Size Determination
Principle/Purpose:
The particle size distribution of active ingredients and excipients is an important physical
characteristic of the materials used to create pharmaceutical products. he'sizey distribution and
‘appearance of the end produit. The link between particle size and product performance is well
documented with regards to Masoiton absorption rites wd eontent sor 7
Theory:
Introduction and overview:
M
romeritics:
Poly disperse powders consist ofiparticles differing in size or density.
r
Mono disperse powders co
of particles Kavitig same size or density.)
Impot
ize Determinat
Particle size can affect
«+ (EBGEWTRiuIORRRAMIE (APL oc excipient) such os flow sixing, compadtion ee
+ [Rate of absorption of drug depend upon its particle size, Small particle size has greater
solubility hence more rate of absorption.
\ fadide soe VAshubfey TRate oh Nagin + ina formulation appearance and sai depend upon the parle size Elegance of
pharmaceutical preparations such as emulsion, suspension, ointments depend upon the
particle size of the disperse phase.
‘Methods for Determining Particte Size:
* Microscopy,
+ Sieving
+ Sedimentation techniques
Advantages
Bach particle individually examined detest ageregats;2D (dimension) shapes
Disadvantages
Time consuming - high operator fatigue - few particles examined.
Sieve analysis is performed using a hest or stack of sieves where each lower sieve has a smaller
‘aperture size than that ofthe sieve above it. WEN Gc one
Sieve number
Sieves can be referred to either by their aperture size mesh size = sieve number
Gio sizes are based on te number of openings per linear inch)
Advantages
We ball yas
© Economical method
+ Easy to perform Disadvantages
© liso suitable yee Tess than. 5Oumy
+ Particles egate during sieving due to generation of electrostatic charges.
+ Particles may clog the sieve apertures.
Sioves
Control no —_|
Very tne
Mechanical sieve shaker
the pipette method) measures the settling rate of particlesin liquid medium
‘Wis defined as the angle possible between surface of a pile of powder and the horizontal planes
of material,
Angle of repose is one of the methods used to assess th
nvder flow:
Four reported methods for testing powder flow are (1) angle of repose, (2) compressibility index
or Hausner ratio, (3) flow rate through an orifice, and (4) shear cell y
‘The two methods most commonly used to measure the angle of repose:
+ ‘Fixed height cone’ method: © "Fixed base cone' method: The granular material flows through a funnel, which is raised
vertically until the heap covers a circular base of fixed size.
al ‘Table, Relationship between angles of reposes and flow properties of powder
~ Angle of Repose (degrees) Flow Property
po 25-30 fine Excellent
ae 31-35 Good =
=) ae Fait—aidnot needed
4-45 Passable—may hangup
[ge 46-55 Poor—must agitate
ww 56-65 Very poor i
More than 66 Very, verypoor
‘Thelftctors that influence the angle of repose of the materials are as follows,
Ee oo tojirregular shape particle duc tova
‘Very fine particles may reveal cohesiveness owing to the electrostatic effect which increases the
angle of repose,
Angle of repose is a characteristic related to
+ The addition o
fumed silicon
+ Removing moisture.
+ Increasing the particle size by making granules
s| Object:
‘To determine the angle of repose and size of the given powders (lactose, starch, talcum)
Glassware:
1. Funnel
‘Tripod stand
Petri dish
Ren
Electronic balance
Chemie:
1. Lactose
2, Starch
3. Talcum
Procedure:
1, Weigh 40 grain of the powder.
2. Transfer it on the funnel previously mounted on the stand.
3. Place the ointment slab beneath the apertuie of the funnel.
4, Allow the powder to pass through the aperture of formes
ointment slab.
d and collect the powder on the
Measure the height and diameter of the pile formed of powder on the ointment slab,
6. Calculate the angle of repose and predict about the flow properties.
Observation
Powder Height (em) Diameter (em)
Talcum 34 2
Starch 3% i
Lactose % wD -
6| Calculations:
A
FORMULA: tang ="
r
a
fee
2
Result;
°
Angle of repose of starch =_34\
Angle of repose of lactose=_>\
20°
Angle of repose of talcum
Discussion
A es valter, the Slow of
stauch is Penable , sre latore Is abso prnolde
adh Haleum is 30" So WS Good m nalne Aa
sey
TIP Objective: Particle Size Determination
ts constitute a category of tableting excipients added externally to a formulation (@leniianiee
eat ineonjetion wily
of the ity during tableting leading to the formation
of tablets uniform in weight and content and devoid Of defects associated with sticking?
Glidant is alonstoxiogpliarmacologically inactivejsubstance used to optimize the flow properties
of tablet granulation or powder materials by decreasing interparticle friction and cohesion, At a
certain range of concentrations.
Lubricants:
Lubricant is a OHetoxic, [phaiiacologieally inactive substance added to the formulation [Oy
deerease fiction between tablet's surface ad the: dle Wall cavity ig which the tablet was formed
andifo Feduce Wear and tear OF dies and punches!
dvantages of Gli and Lubricant:
Glidant;
+ (Smooth low of powder granules/during solid dosage from manufacturing.
+ Helps {0imaintain uniformity of powder mixture of API and/or excipients
+ Indirectlyprevent weight variation/
8] Many hbicants may prove ROW
Reducing Wear On FuBBingSuraes Object:
To study the particle size and effect of glidant on flow properties of powder sample
Requirements:
Glassware:
Funnel
Tripod stand
Petri dish
lectronic balance
Chemicals:
2
Powder
Glidant
Accurately weigh the powder sample (10g) on balance.
Determine the angle of repose of the sample
Now calculate 1.$% of your bulk: weight and weigh the glidant as per calculated amount.
Mix the glidant into your sample of which angle of repose is pre-determined.
Misi
Repeat the procedure for angle of repose with this mixture.
should be proper and uniform.
Calculate the angle of repose of the sample and the mixture and compare the results.
Wash all the glass ware with tap water and return it.
Observatio
10.
Weight of sample: hs}
Weight of glidant: no
10] Sr. | Name of the | Height of pile | Mean | Diameter of | Mean
‘Angle
no. | powder a height | pile diameter | of
(cm) (em) (cm) ete
1 | Sample ra
Qt DZ [8-6] \o q-3B 3
Mixture 2.5 wy
4S 2.5 [3.295525 4.25 | Be
Calculations:
For sample:
h
tand = _
R
We Lom
a= 43
(raj d
bree of mrepoxe = ! )
2 jan! (2%2)
poe
AS
a dan 0.43)
ul For mixture:
canoe
k= 2-5em
A = U5 om
Prager epee = en an)
a A
vA
Kos
~ dann)
&e
\
"
I Results:
“> ff magma Angle dod “ee, SS
w> Bila sheng fi oertin. pal Slay BA
Discussion:
Pune Tram AOR = HO ulidy tomer under Whe
range O, C36- 40") amd owes ‘
Aaa SBTHA ond com lee vsedh we
ee Rad mbar her hop = 86 Unda
(>c6?) wwdr 18
ay wh tor es nt ees G con't be ee ‘wn
ope aunbedion ox rablethno, fecraye it will dweky
dholle Se oiGce of open Determination of Porosity
Objectiv
Pi
‘The porosity of pharmaceutical materials and medical devices/éait impact)prodiction, material »
_movement, and pharmacokinetic behaviory Tablet porosity determines the tensile strength
‘Theory:
troduction and overview:
volume.
rue vel
Bulk density:
‘The bulk density of a powder is the ratio of themass 6f an untapped powder sample and its volume
Tapped Dansitv: (Wirimum Packed Volume)
‘The tapped density of a material is the ratio of the:mass'to the tapped volume (excluding the
{imerparticulate yoid volume) of a tapped powder sample
mass
Tapped density = ea volume
41 “The tapped density is obtained by mechanically tapping a graduated cylinder containing the sample
until little further volume change is observed) IPs the wiaximum packing density of a powder (or,
blend of powders) achieved under the influence of Well defitied, externally applied forces!
“TRO aR AEKEA|Volkime thus achieved depends on a number of factors including PaHICIe
size distibutiony true density particle tape’ and Gokesiveress de t0 surface forces including
‘moisture, Therefore, the tap density of a material can be (ised to predict both its flow properties)
‘The tapped density depends on:
+ Thegiuimnauaitheiadenysed
+The numberof times the powders tapped to achieve the tapped density
+ The mitss/of material sed in the test
Seale of Flow-ability
Compressibility index [Flow character | Hausner ratio
(percent)
1-10 Excellent 1.00-1.11
1-1 Good LAZLAS
16-20 Fair 1.19-1.25
21-25 Passable 1.26-1.34
26-31 Poor 135-145
32.37 Very poor 146-159
>38 Very, very poor |> 1.60
asiy Recommended flow properties according to B.P
T 1-10 ~| Excellent
2 1-15 ~ | Good
3 16-20 Fair
a 21-25 Passable
3 26-31 Poor
6 32-37 Very poor
7 338 Very, very poor
16 | Object:
“To determine % Porosity of the given powders.
Requirements:
Glassware:
1. Measuring cylinder
2. Analytical balance
3. Petri dish
Chemicals:
Lactose
starch
Taleum
Procedure:
Weigh 10 gram of the powder.
‘Transfer the powder into the measuring cylinder and record the volume (Vo)
Start tapping the cylinder with 2 second time interval for 50 times.
‘After tapping, record the final volume (V1).
Calculate the porosity for the given powders and predict about the flow properties
wie vation
Sr Name ofthe | Volume “before | Mean | Volume after tapping | Mean *» |
no, | powder tapping ( Vo) (voy [WD vey | Porosity
TT pach | 35M Sh] Bontf23ed aT md | 25nd) 327,
FT pacer [2059] 23-5 ed) ae iad | rd fisad | B1-/-
5 Tracer [54ent | Clin) [60m Sead [UY Ird |ogmd | 3401
Calculations:
STARCH? ne = {Og m)
Rac yi tes 0 > =\s
* age = O21 Tapped Aonatty= 12. = 0-4
Cas mars fine — Powe sige
Pee
«we
y
VT 2 wd. 0
Tacos Cua~ gn)
Go- wc. 08 4 TDF A
a2 1S
= 2:66 ~0.US xiv0
obo
LACTOSE (Ute 20g)
Bp» 1 - 6s $00" a ese
34
60
6. Bin = 6,333 Rio
18 |
0.512 Result:
‘The Porosities of the given powders are as follows:
Discussion:
Tre yoronite, vatue sugaeits hat Brak Glade
Leste Jal mo che Same category of Gor
oy OTe Tahu une 9 ON Mproreel
woe Gate OPER gmat fast sto “fore”
calpy
a9} 34 eck
“To determine the particle size by sieving method.
nin it
Glassware:
1, Blectronic balance
2, Mechanical sieve shaker
Petri dish
Chemicals:
1. Powder
Procedure:
1, Arrange set of sieve in descending order (the sieve of largest pore size on the top followed
by sieves of gradually decreasing pore size).
Weighed 30 g of given powder.
Pour that powder on the top sieve of the sieve set.
Tum on the sieve shaker for 5 min.
wen
After § min, stop the sieve shaker and collect the powder material retained on each sieve
separately.
6. Weighed the retained powder collected from each sieve. Observation:
Percent weight
~ Sieve no ‘Aperture size (jum)
(particle size) retained
[> glowee| 2000
