Aim: To prepare conventional tablet formulation containing hydrophilic and hydrophobic API and to study effect on dissolution rate

a) Hydrophilic API by direct compressionb) Hydrophilic API by wet granulationc) Hydrophobic API by direct compression

Formula:

a) Each tablet contains 500 mg Metformin, Excipients quantity sufficient.b) Each tablet contains 500 mg Metformin, Excipients quantity sufficient.c)

Batch size: 20 tablets

Packaging: Aluminum strips of 10 tablets.

Formulation:

a) Metformin by wet granulation.

Ingredients Formula for one tablet

Formula for 20 tablets

Role of each ingredient

Metformin 500 mg 10 gm DrugPolivinyl pyrollidon

62.5 mg 1.25gm Binder

Microcrystalline cellulose

62.5mg 1.25gm Filler

Crosscarmalose Sodium

12.5 mg 0.25gm Superdisintegrant

Magnesium Stearate

6.25 mg 0.125gm Lubricant

Purified water q.s. q.s Granulating fluidTotal 643.75 mg 12.875 gm

b) Metformin by direct compression.

Ingredients Formula for one tablet

Formula for 20 tablets

Role of each ingredient

Metformin 500 mg 10 gm DrugHydroxy Propyl Methyl Cellulose

77.90 mg 1.558 gm Diluent

Povidone 26.8 mg 0.536 gm BinderColloidal Sillica 3.25 mg 0.065 gm GlidentMicro Crystalline Cellulose

36.85 mg 0.737 gm Diluent

Magnesium Stearate

5.2 mg 0.104 gm Lubricant

Total 650 mg 13 gm

Procedure:

1. Method of preparation All the ingredients were weighed accurately. Metformin and Polivinyl pyrollidon, Microcrystalline cellulose were

taken in mortar and pestle and grinded together to have uniform mixing and obtain fine powder.

Lump mass was obtained by using purified water as granulating agent. Pass this lump mass through 10# sieve and granules obtained. The granules were collected on the paper and allowed to dry in oven at

45°C for 1 hour. After drying the mass was passed through 20# sieve and granules were

retained on 40# sieve. At the end, 1% w/w of croscarmellose sodium and 2% w/w of the

lubricant magnesium stearate were added and mixed for 5 minutes. Fines obtained were weighed. 15% of fines were added to the dried granules and pack in zip lock bag

and punched into tablets using tablet punching machine. Tablets were then evaluated.

2. Method of characterizationi. Weight variation: A total of 20 tablets were taken and each tablet were weighed

accurately. Average of 20 tablets was calculated and percentage weight

variation was calculated using following formula. % weight variation = x-x avg /x avg *100

ii. Hardness: Hardness of tablet was determined by using Monsanto hardness

tester®.iii. Friability:

20 tablets were weighed and placed in the apparatus where they were exposed to rolling and repeated shocks.

They fell 6 inches in each turn within the Roche apparatus. After 100 revolutions of apparatus the tablets were weighed and

the weighed to compare with initial weight. The loss due to abrasion was a measured of table friability. The value was expressed in percentage.

Observations:i .Observation table of weight variation

Sr.no.

Weight of tablets(x) x-x avg x-x avg /x avg *100a B c a b C a b c

1234567891011121314151617181920Avg.

iv. Disintegration time One tablet was put into each tube, assembly was suspended

in the beaker containing distilled water and operated with the 10# discs.

Time was recorded required to disintegrate tablet and its pattern.

Remove the assembly from the liquid.

v. Dissolution study In vitro dissolution study of metformin tablets was

performed using phosphate buffer pH 6.8 maintained at a temperature of 37 ± 0.5°C in USP II dissolution test apparatus and at rotation speed of 100 rpm.

Samples were withdrawn time interval (5, 10, 15, 20, 30, 45 and 60 min), and filtered through Whatman filter paper.

Absorbance of suitably diluted samples was determined by UV spectrophotometer at 236 nm and the percentage of drug release was calculated.

ii. Hardness of tablet:

a.)

b.)

c.)

iii. Disintegration time:

a.)

b.)

c.)

iv. Observation table of Friability

Formulation Initial weight of tablet(a)

Final weight of tablets(b)

(a)-(b) (a)-(b)*100 (a)

abc

vi. Observation table of DissolutionT

ime

Abs

rban

ce

Con

c.(m

cg/m

l)

Con

c. *

dil

. F

acto

r

conc

(mcg

/5m

l)

Con

c.(m

cg/9

00m

l)

Cum

.con

c(m

cg/5

ml)

Tot

al

mcg

/900

ml

Tot

al

(mg/

900m

l)

%D

R

Sr.no.

Time(min.) absorbance Conc.per ml.

Conc.in 900 ml

Cumulative conc.

% drug release

a b c a b c a B c a b c a b c1 02 103 204 305 406 507 60

Comments:

1.) Hydrophilic API can be crystalline powder having average to good flowability. It can be formulated by direct compression or wet granulation method. While hydrophobic API has poor flow and can only be formulated by wet granulation method which will improve flow.

2.) Physicochemical nature of API affects sets of disintegration, deaggregation and also dissolution. In case of hydrophilic API steps are not rate limiting while for hydrophobic API formulation should facilitate sequences of steps. This can be achieved by wet granulation method using proper binder.

3.) In present study effects of method of preparation on rate limiting step is investigated. Observation show…