CHAPTER – 6 PREFORMULATION STUDIES
PRE-FORMULATION STUDIES
Prefomulation studies involve the determination of both physical and chemical properties of
drug to produce a new drug that is safe, stable and efficacious. These pre-formulation studies
are carried out prior to the formulation of drug. The objectives of these studies are, to establish
the compatibility of drug and excipients used in the formulation and to obtain an optimal drug
delivery system.
1. Material and methods
All materials (AR Grade) used were obtained from different sources and all instruments
used in work that are as given in list respectively.
2. List of materials –
Micro crystalline cellulose, Tween 80 , Poly ethylene glycol, Propylene glycol, Magnesium
stearate and HPMC K100 and Talc.
3. List of Instruments –
UV/VIS Spectrophotometer (UV-1700, Shimadz Corporation, Japan), Electronic balance ,
Mechanical stirrer and pH meter .
Prefomulation studies involve the determination of both physical and chemical properties
of drug with the goal of producing a new drug which is safe, stable and efficacious. These
preformulation studies are carried out prior to the formulation of drug. The objectives of
these studies are, to establish the compatibility of drug and excipients used in the
formulation and to obtain optimal drug delivery system.
4. Identification of pure drug
• Melting point determination:
• The melting point is the temperature at which the pure liquid and solid exist in equilibrium
at an external pressure of 1 atmosphere. Thiel’s tube method of melting point determination
in liquid paraffin was used in the present study
• Solubility studies:
• Solubility studies of Lovastatin were carried out in methanol, phosphate buffer 7.4, PEG
200, and Tween 80. Saturated solutions were prepared by adding excess drugs to the
vehicles and shaking on the shaker for 48 hr at 25 °C under constant vibration. Filtered
samples (1 ml) were diluted appropriately with 0.1N hydrochloric acid solution and
Lovastatin was determined spectrophotometrically at 238 nm. The average value of three
trials was taken. Results are shown in Table no 2
FORMULATION AND EVALUATION OF LOVASTATIN BASED SUSTAIN RELEASE MATRIX TABLET Page 68
CHAPTER – 6 PREFORMULATION STUDIES
• Determination of absorption
Maximum (λ max) The wavelength at which maximum absorption of radiation takes place
is called as λ max. This λ max is characteristic or unique for every substance and useful in
identifying the substance.
Accurately weighed 100 mg of Lovastatin was dissolved in 0.1N NaOH buffer taken in a
clean 100 ml volumetric flask. The volume was made up to 100 ml with the same which
will give stock solution-I with concentration 1000 µg/ml. From the stock solution-I, 5 ml
was pipette out in 50 ml volumetric flask. The volume was made up to 50 ml using 0.1N
NaOH buffer to obtain stock solution-II with a concentration 100 µg/ml. From stock
solution-II, 1ml was pipette out in 10 ml volumetric flask. The volume was made up to 10
ml using 0.1N NaOH buffer to get a concentration of 10 µg/ml. This solution was then
scanned at 200-400 nm in UV-Visible double beam spectrophotometer to attain the
absorption maximum (λ-max).
• Preparation of standard calibration curve for lovastatin:
10 mg of pure drug was accurately weighed and transferred into the 10 ml volumetric flask.
The volume was made up using 0.1N NaoH to get a concentration of 1000 µg/ml. From this
solution, 1 ml was withdrawn into a 10 ml volumetric flask and it was diluted to 10 ml with
distilled water to get a concentration of 100 μg/ml. From this 0.5 ml, 1 ml, 1.5 ml, 2 ml, 2.5
ml, and 3.0 ml were pipetted out into a 10 ml volumetric flask and diluted to 10 ml using
distilled water to get concentrations of 5 μg/ml, 10 μg/ml, 15 μg/ml, 20 μg/ml, 25 μg/ml,
30 μg/ml respectively. The absorbance of this solution was measured at 238 nm using a UV
Spectrophotometer against a blank.
• Drug excipient compatibility:
IR spectra scanning of pure drug Lovastatin, excipients 11 compacts were done in
potassium bromide pellets at a moderate speed between 400 to 4000 cm -1.
• Pre-compression studies (Flow properties):
The flow ability of a powder is of critical importance in the production of pharmaceutical
dosage forms to get a uniform feed as well as the reproducible filling of tablet dies,
otherwise, high dose variations will occur. To ensure the flow properties of the liquid-solid
systems, angle of repose measurements, Carr’s index and Hausner’s ratios were adopted.
FORMULATION AND EVALUATION OF LOVASTATIN BASED SUSTAIN RELEASE MATRIX TABLET Page 69
CHAPTER – 6 PREFORMULATION STUDIES
• Angle of repose (θ):
The angle of repose of powder blend was determined by the funnel method. The accurate
weight of powder blend was taken in the funnel. The height of the funnel was adjusted in
such a way that the tip of the funnel just touches the apex of the powder blend. The powder
blend was allowed to flow through the funnel freely onto the surface. The diameter of the
powder cone was measured and angle of repose (θ) was calculated using the following
equation. θ= tan-1 h/r Where, h and r are the height and radius of the powder cone
• Bulk density
Both loose bulk density (LBD) and tapped bulk density (TBD) was determined. A quantity
of 2 gm of powder blend from each formula, previously shaken to break any agglomerates
formed, was introduced into 10 ml measuring cylinder. After that, the initial volume was
noted and the cylinder was allowed to fall under its own weight onto a hard surface from
the height of 2.5 cm at second intervals. Tapping was continued until no further change in
volume was noted. LBD and TDB were calculated using the following equations.
o LBD= Weight of the powder blend/Untapped Volume of the packing
o TBD=Weight of the powder blend/Tapped Volume of the packing
• Compressibility index
The Compressibility Index of the powder blend was determined by Carr’s compressibility
index. It is a simple test to evaluate the LBD and TBD of a powder and the rate at which it
packed down. The formula for Carr’s Index is as below.
Carr’s Index (%) = [(TBD-LBD) x100]/TBD
• Hausner’s ratio:
Hausner’s ratio was calculated from the equation Hausner’s ratio = Tapped density/Bulk
density
FORMULATION AND EVALUATION OF LOVASTATIN BASED SUSTAIN RELEASE MATRIX TABLET Page 70
