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METHODOLOGY
MATERIALS
Avicel pH 102
ESSEL Fine Chem,Mumbai
(Microcrystalline cellulose)
EQUIPMENTS
MRR. COLLEGE OF PHARMACY Page 44
METHODOLOGY
METHODOLOGY
a) PRE-FORMULATION STUDIES
Pre-formulation testing is an investigation of physical and chemical properties of a drug
substance alone and when combined with excipients.
Pre-formulation studies yield necessary knowledge to develop suitable formulation for
toxicological use. It gives information needed to define the nature of the drug substance and
provide a dosage form. Hence, the following pre-formulation studies were performed for the
obtained sample of drug.
PRE-FORMULATION STUDIES
Pre-formulation testing is an investigation of physical and chemical properties of a drug
substance alone and when combined with excipients.
Pre-formulation studies yield necessary knowledge to develop suitable formulation for
toxicological use. It gives information needed to define the nature of the drug substance and
provide a dosage form. Hence, the following pre-formulation studies were performed for the
obtained sample of drug.
Melting point:
The melting points of loratidine were found out by capillary method using programmable
Accurately weighed 100 mg of drug was first dissolved in100 mL of 6.8 pH Phosphate buffer in
100 mL of volumetric flask to make a concentration of 1000 g/mL (primary stock solution). 5
mL of primary stock solution was pipetted out into 50 mL of volumetric flask and volume was
adjusted with 6.8 pH Phosphate buffer to make a concentration of 100g/mL (secondary stock
solution).
2. Sample Preparation
From the secondary stock solution pippetout 0.2,0.4,0.6,0.8 and 1ml in to 10ml of volumetric
flask and volume made up to with 6.8 pH Phosphate buffer Fto give various concentrations such
as 2,4,6,8,10g/mL were prepared for calibration curve. Standard curve was plotted by taking
absorbance of secondary stock solutions in UV double beam spectrophotometer at 245 nm.
Absorbance at 245nm
SD, n=3
Concentration in mcg
0.0550.011
2
0.1050.012
4
0.1650.014
6
0.2120.012
8
0.2660.016
10
0.3
0.15 Abs
Linear (Abs)
0.1
0.05
0
1 2 3 4 5 6 7 8 9 10 11
interaction between the drug and excipients used in the formulation.1-2 mg of solid fine powder
of loratidine and 200-300 mg of dry powder of KBr (IR grade) were taken in a mortar and mixed
well with the help of a spatula. Spectrum measurement was carried out using KBr disk method in
physical mixture was compared with that of the pure drug to check any possible drug-excipient
interaction.
Bulk density
Bulk density of a compound varies substantially with the method of crystallization,
milling or formulation. Bulk density is determined by pouring pre sieved blend into a graduated
cylinder via a large funnel and measure the volume and weight.
Bulk density = weight of blend
Bulk volume of blend
Bulk density was expressed in g/cc.
Tapped density:
Tapped density is determined by placing a graduated cylinder containing a known mass
of blend and mechanical tapper apparatus, which is operated for a fixed number of taps until the
powder bed volume has reached a minimum volume. using the weight of the drug in the cylinder
and this minimum volume, the taped density may be computed.
Tapped density = weight of blend
Excellent <10
Good 11 15
Fair 16 20
Possible 21 25
Poor 26 31
Very poor 32 37
Hausners Ratio:
It indicates the flow properties of the powder and ratio of Tapped density to the Bulk
density of the powder or blend.
Hausners Ratio = Tapped density/Bulk density
Table-5 Flow Properties and Corresponding Hausners ratio
Angle of repose:
The manner in which stresses are transmitted through a bead and the beads response to
applied stress are reflected in the various angles of friction and response. The method used to
find the angle of repose is to pour the powder ion a conical heat on a level, flat surface and
measure the included angle with the horizontal.
Tan = h/r
Where, h= height of the heap
r= Radius of the heap
Table-6 Flow Properties and Corresponding Angle of Repose
A series of sieves were arranged in the order of their decreasing pore diameter (increasing
sieve number) i.e. sieve number 20, 30, 60, 80, 100, collector. 30 grams of blend was weighed
accurately and transferred to sieve 20 which is kept on top. The sieves were shaken for about 5-
10 minutes. Then the drug retained on each sieve was taken, weighed separately and amount
retained was expressed in terms of cumulative percentage retained.
camphor and menthol as sublimating agents. The concentrations of the above ingredients were
optimized as shown in below table on the basis of trial preparation of the tablets. All the
ingredients were weighed accurately. The drug was mixed with the release rate enhancing
disintegrants and other excipients, except magnesium stearate, in ascending order of their weight.
The powder mix was blended for 20 min to have uniform distribution of drug in the formulation.
Then, magnesium stearate was added and mixed for not more than 1 min (to ensure good
lubrication.) About 200 mg of the powder mix was weighed accurately and fed into the die of
single punch machinery and compressed using 8 mm flat- surface punches. The hardness of the
Compression
Ingredients F1 F2 F3 F4 F5 F6 F7 F8
Physical appearance:
The general appearance of tablets, its visual identity and overall elegance is essential for
consumer acceptance. The control of general appearance of tablet involves measurement of
number of attributes such as tablet size, shape, colour, presence or absence of odour, taste,
surface texture and consistency of any identification marks.
Hardness test:
This is the force required to break a tablet in a diametric compression. Hardness of the
tablet is determined by Stocks Monsanto hardness tester which consists of a barrel with a
compressible spring. The pointer moves along the gauze in the barrel fracture.
Friability:
This test is performed to evaluate the ability of tablets to withstand abrasion in packing,
handling and transporting. Initial weight of 20 tablets is taken and these are placed in the
friabilator, rotating at 25rpm for 4min. The difference in the weight is noted and expressed as
percentage. It should be preferably between 0.5 to 1.0%.
%Friability = (W1-W2)/W1 X 100
Where, W1= weight o f tablets before test
W2 = weight of tablets after test
It is desirable that all the tablets of a particular batch should be uniform in weight. If any
weight variation is there, that should fall within the prescribed limits:
Disintegration test:
Disintegration time is considered to be one of the important criteria in selecting the best
formulation. To achieve correlation between disintegration time in-vitro and in-vivo, several
methods were proposed, developed and followed at their convenience. One tablet was placed
into each tube and the assembly was suspended into the 1000ml beaker containing water
maintained at 372oc and operated the apparatus for 15 minutes. The assembly was removed
from the liquid and the tablets were observed. If one or two tablets fail to disintegrate
completely, repeat the test on 12 additional tablets. The requirement is met if not less than 16 of
the total of 18 tablets tested are disintegrated.
Dissolution test:
Dissolution: It is the amount of the solid substance that goes into the solution per unit time under
standard conditions of the temperature and pressure
Method: Dissolution media was taken as 6.8 pH Phosphate buffer, 500ml was placed in the
vessel and the USP apparatus 2 (paddle) was assembled. The medium was allowed to
equilibrate to temp of 37 + 0.5C. Tablet was placed in the basket and placed in the vessel, the
apparatus was operated for 15min at 50 rpm. At definite time intervals, 5 ml of the fluid was
withdrawn; filtered and again 5ml of the fluid was replaced. Suitable dilutions were done with
the dissolution fluid and the samples were analyzed using UV.
Dissolution parameters:
Temperature: 375oC.
Assay
The Assay for loratidine porous tablets was estimated by UV spectrophotometer at 245nm.
STABILITY STUDIES:
FDA and ICH specifies the guidelines for stability testing of new drug products, as a
technical requirement for the registration of pharmaceuticals for human life.The ICH tripartite
guidelines have established long term stability testing to be done at 25 0C/60%RH for 12 months.
Accelerated stability testing should be done at 40 0 C/75%RH for 6 months and stability testing at
intermediate storage conditions should be done at 300C/65%RH. The following table shows
different storage conditions and period of stability testing.