Professional Documents
Culture Documents
Chapter-4 Materials and Methods PDF
Chapter-4 Materials and Methods PDF
The following raw materials were used for the formulation of fast dissolving tablets:
Equipments and instruments used for the preparation of Fast dissolving tablets are given in
table below:
4.2 METHOD
4.2.1 PRE-FORMULATION STUDIES:
Pre-formulation study is the first step in the development of dosage form of a drug
principles are applied to determine the physicochemical parameters of a new drug substance
To generate useful information about the drug to the formulator to design an optimum
The FTIR spectrum of the sample of the drug was compared with the standard FTIR spectra
Solubility Analysis
Solubility analysis is carried out for Montelukast Sodium samples in various solvents. 10
mg pure drug was dissolved in 10ml of different solvents i.e. water, ethanol and dimethyl
Standard stock solution of Montelukast Sodium was prepared in 0.5% SLS working standard
solution of Montelukast Sodium was prepared by taking suitable aliquots of standard drug
solution (1000µg/ml) and volume was made up to 10ml with 0.5% SLS. The resulting
solutions were then scanned in the UV range (200-400) using UV double beam
spectrophotometer using blank. The spectrum of absorbance versus wavelength was recorded
Accurately weighed 100mg of Montelukast Sodium was dissolved with 0.5% SLS in 100ml
volumetric flask. From this stock-I, 10ml was pipette in 100ml volumetric flask and volume
was made with 0.5% SLS to make second solution. From the second stock solution different
aliquots were prepare solution in the range 5-30µg/ml. The standard curve was obtained by
Method of preparation
crospovidone, gellan gum, guar gum and sterculia gum according to the formulae given in
Table 4. The average weight of the tablet was taken to be 180mg. The ingredients were
seived through a 60# mesh and then the required quantities weighed. All the ingredients
except magnesium stearate. After mixing the drug and the excipients for 20 min, magnesium
stearate were added and further mixed for additional 2 min. The tablet mixture was then
machine (Cadmach). 3
Ingredients F1 F2 F3 F4 F5 F6 F7 F8 F9
Montelukast 10 10 10 10 10 10 10 10 10
Sodium
Crospovidone 20 30 40 - - - 20 30 20
SSG - - - 20 30 40 - - -
Guar gum - - - - - - 20 10 -
Gellan gum - - - - - - - - 20
Sterculia gum - - - - - - - - -
Stevia leaf 9 9 9 9 9 9 9 9 9
powder
Mannitol 15 15 15 15 15 15 15 15 15
Magnesium 3.6 3.6 3.6 3.6 3.6 3.6 3.6 3.6 3.6
stearate
MCC pH 101 122.4 112.4 102.41 122.4 112.4 102.4 102.4 102.4 102.4
Total 180 180 180 180 180 180 180 180 180
Ingredients F10 F11 F12 F13 F14 F15 F16 F17 F18
Montelukast 10 10 10 10 10 10 10 10 10
Sodium
Crospovidone 30 20 30 - - - - - -
SSG - - - 20 30 20 30 20 30
Guar gum - - - 20 10 - - - -
Gellan gum 10 - - - - 20 10 - -
Sterculia gum - 20 10 - - - - 20 10
Stevia leaf 9 9 9 9 9 9 9 9 9
powder
Mannitol 15 15 15 15 15 15 15 15 15
Magnesium 3.6 3.6 3.6 3.6 3.6 3.6 3.6 3.6 3.6
stearate
MCC pH 101 102.4 102.4 102.4 102.4 102.4 102.4 102.4 102.4 102.4
Total 180 180 180 180 180 180 180 180 180
Note: weight per tablet is 180mg containing montelukast equivalent to 10mg montelukast.
Bulk Density:
a) Bulk Density: Accurately weighed of powder from each formulation previously passed
through 20-mesh sieve, was transferred into a graduated cylinder via a large funnel. The
powder in the cylinder was leveled without compacting, and the unsettled apparent volume
(V0) was noted. The apparent bulk density (g/ml) was calculated by the following
formula;
b) Tapped density: Accurately weighed of powder from each formulation, which was
previously passed through 20-mesh sieve, was transferred into a graduated cylinder.
Then the cylinder containing the sample was mechanically tapped by raising the cylinder
and allowing it to drop under its own weight using Bulk density apparatus. The density
apparatus was set for 100 taps and after that, the volume (Vf) was measured and continued
operation till the two consecutive readings were equal. The tapped bulk density in gm/ml
c) Carr’s Index
compressibility index. It is a simple test to evaluate the BD and TD of a powder and the
rate at which it is packed down. The formula for Carr’s Index is as below:
d) Hausner’s Ratio
The Hausner’s ratio is a number that is correlated to the flowability of a powder or granular
Hausner’s Ratio = TD / BD
Table No. 6 : Effect of Carr’s Index and Hausner’s Ratio on flow property.
e) Angle of repose
The angle of repose of powder was determined by the fixed funnel method. Powder was
taken in the funnel. The height of the funnel was adjusted in such a way that the tip of
the funnel just touched the apex of the conical pile of the blend. The blend was allowed
to flow through the funnel freely on to the graph paper that is placed on a flat
horizontal surface. The diameter of the base of the powder cone was measured and angle
θ = tan-1( h /r)
Where, ‘θ’ = angle of repose
< 20 Excellent
20-30 Good
30-34 Passable
A successful formulation of a stable and effective solid dosage form depends on careful
selection of excipients that are added to facilitate administration, promote the consistent
Compatibility studies of pure drug Montelukast Sodium with polymers and other
excipients were carried out prior to the preparation of tablets. Compatibility of Montelukast
Sodium with the polymers used in the formulation and the physical mixture of final
composition after combining with the excipients were investigated by comparing FTIR
spectra of the sample mixture with that of the pure drug. 47,48
The formulated tablets were visually observed for its shape and colour
Weight variation of tablet was determined by analytical weighing balance. Twenty tablets
were selected randomly from each batch and weighed individually. The average and standard
deviation were then calculated. The specifications for weight variation and percentage
80 mg or less 10
250mg or more 5
b) Uniformity of thickness:
Three tablets of each formulation were picked randomly and dimensions were measured
c) Hardness test:
Three tablets were randomly picked from each batch and hardness is expressed in kg/cm2.
d) Friability test:
Roche friabilator was used for friability test. Ten uncoated tablets from each
formulation were weighed (Winitial) accurately, placed in the friabilator and rotated at 25 rpm
for a period of 4 min. Tablets were again weighed (Wfinal) and the percentage weight loss in
F= %
mg Montelukast Sodium was dissolved in 100 ml volumetric flask with water 100µg/ml of
the drug concentration was made. Then solution was filtered and further dilutes 1ml solution
in 10 ml volumetric flask and diluted with water. The solution was analyzed UV
using standard calibration curve of the drug. Drug content was studied in triplets for each
batch of formulation.
Disintegration test for uncoated tablets was carried by placing one tablet in each
tube of the basket and top portion of the each tube was closed with disc. The
disintegrating apparatus was run using 0.5% SLS maintained at 37±20C. The assembly
was raised and lowered between 30 cycles per minute. The time taken for complete
disintegration of the tablet with no palpable mass remaining in the apparatus was measured
and recorded. The experiments was carried out in triplicate from each formulation.
Drug release studies of 6 uncoated tablets from each formulation were carried
out using a USP XXIII dissolution rate test apparatus (Apparatus 2, 50 rpm, 37 °C) for 5
minutes in 0.5% SLS (900 ml). The samples were withdrawn at time intervals 1, 2, 3, 4, 5,
6 and 5 minutes and directly analyzed for Montelukast Sodium content using UV
spectrophotometer at 240 nm. Suitable volume of the dissolution media was added after
The cumulative amount of Montelukast release at different time intervals from the different
formulation of tablets were fitted to zero order kinetics, first order kinetics, Hixson-Crowell
release.
Zero order release: Zero order release kinetics refers to the process of constant drug
release from a drug delivery device. It describes the system in which the release rate is
independent of its concentration. In its simplest form, zero order release can be represented
as: Q = Q0 + K 0 t
If the zero order drug release kinetic is obeyed, the plot of cumulative % drug release [Q] vs.
First order release: This model has also been used to study absorption and/or
elimination of drugs. It describes the drug release from the system in which the release rate is
concentration dependant. The release of the drug which followed first order kinetics can be
= - K 1C
Log C = log C0 -
If the release pattern of drug follows first order kinetics, then a plot of log of cumulative
drug remaining [ log (C0 - C)] vs. time[t] will be straight line with a slope of K1/2.303 and an
intercept at t= 0 of logC0.
particles’ regular area is proportional to the cube root of its volume. They derived the
If the Hixson-Crowell drug release kinetic is obeyed, the plot of cube root of drug amount to
1/3 1/3
be released [W0 - Wt ] vs. time[t] will be straight line with a slope of KHC and an
intercept at W0 1/3.
Higuchi Model: Higuchi tried to relate the drug release rate to the physical constants
based on simple laws of diffusion. Higuchi derived an equation to describe the release of a
drug from an insoluble matrix as the square root of a time-dependent process based on
Where, Mt and M∞ = cumulative amount of drug release at time ‘t’ and infinite
time respectively.
‘S’ is Solubility,
Mt/M∞= KH * t ½
If the Higuchi model of drug release is obeyed, then a plot of Mt/M∞ versus t1/2 will be
which describes the fractional drug release is exponentially related to the release time. It
adequately describes the release of drug from a polymeric system of slabs, cylinders and
M t/ M ∞ = K t n
If the Krosmeyer-Peppas model of drug release is obeyed, then a plot of log cumulative %
drug release [Log (Mt / M∞)] vs. log time [log t] will be straight line. By incorporating the
first 60% of release data, mechanism of release can be indicated according to Korsmeyer
i) Stability Studies
Stability studies were done to understand how to design a product and its packaging such that
product has appropriate physical, chemical and microbiological properties during a defined
Tablet formulation was subjected for stability studies over a period of 3 months as per
. The tablets were wrapped with aluminium foil and packed in amber colored screw capped
and kept in a stability chamber maintained at 40±2˚C. Samples were taken after 3 month
analyzed for the tablet parameters: colour, thickness, hardness, drug content and in-vitro
dissolution profile. In-vitro drug release at 0 month and after 3 months of stability study was
compared.