The document describes an in vitro bioequivalence study of Glimepiride using biorelevant media. The aim was to evaluate the dissolution rate of Glimepiride in different biorelevant media, compare the bioequivalence of local generic brands to an innovator brand, and predict the effect of food in the GI tract on dissolution. Dissolution studies were conducted in four biorelevant media with two tablets each of three brands. Results showed that dissolution was highest in the intestinal medium and reduced with food. Difference and similarity factors indicated the two generic brands were equivalent to the innovator brand. Using biorelevant media allowed prediction of dissolution rates and bioequivalence of the Glimepiride brands.

1. In vitro Bioequivalence Study of
Glimepiride Using Bio relevant
Medium.

2. Indroduction
• two pharmaceutical products are bioequivalent if they are
pharmaceutically equivalent and their bioavailability (rate
and extent of availability) after administration in the same
molar dose are similar to such a degree that their effects, with
respect to both efficacy and safety, can be expected to be
essentially the same.
• -Drug products in identical dosage forms that contain the
same active ingredient
-the same salt or ester
• -same dosage form
-identical in strength or concentration.
-may differ in characteristics such as shape, scoring
configuration release mechanisms, packaging , excipients.
-when applicable , must meet the same content uniformity,
disintegration times, and dissolution rates.

3. Aim Of The Work
The aim of project work
 To evaluate the dissolution rate of Glimepiride ein
different biorelevant medium.
 To compare the bioequvalence of local generic
Glimepiride with the innovator Glimepiride brand.
 To predict the effect of presence of food in GI tract in
the dissolution of Glimepiride.
 To recommend the ideal medication process of the drug.

4. Drug Profile
Glimepiride
 Glimepiride is a medium- to long-acting sulfonylurea anti-
diabetic drug. It is sometimes classified as either the first
third-generation sulfonylurea, or as second-generation.
 It lowers blood sugar by stimulating the release of insulin by
pancreatic beta cells and by inducing increased activity of
intracellular insulin receptors.
 Its Chemical formula C24H34N4O5S and Molecular mass is
490.617 g/mol.
 Its is usually given in Oral route.

5. Design Of Study
 In vitro dissolution study of three brands of Glimepiride
tablet was carried out in separate biorelevant media of
FaSSGF, FaSSGF, FeSSGF and FeSSIF. Percent release of
two local brand of Glimepiride Diaryl (Beximco) and Secrin
(Opsonin) was compared with the release rate of innovator
brand Lasix (Sanofi Aventis). Two tablets of each brand were
tested in each of the above mentioned medium for up to 4
hours using USP dissolution apparatus II paddle assembly at
50 rpm. temperature was maintained at 37±0.5°C. for
FaSSGF, FeSSGF and FeSSIF 900mL of dissolution medium
was used and for FaSSGF 500mL dissolution medium is
recommended(USP-32).

6. Composition of Dissolution
Medium
Table 1: composition of FaSSGF
FaSSGF pH 1.6
Sodium taurocholate 80µM
lecithin 20 µM
pepsin 0.1gm
Sodium chloride 34.2 µM
HCl q.s. pH 1.6
Distilled water q.s. 1000mL

7. Composition of Dissolution
Medium
Table 2: composition of FaSSGF
FaSSGF pH 6.5
Maleic acid 19.12mM
Sodium taurocholate 3 mM
lecithin 0.2 mM
NaCl 68.62 mM
NaOH 34.80 mM
Distilled water q.s. 500mL

8. Composition of Dissolution
Medium
Table 3: composition of FeSSGF
FeSSGF
Acetic acid 17.12mM
Sodium acetate 29.75 mM
Sodium chloride 237.02 mM
Milk: buffer 1:1
NaOH/HCl q.s. pH 5

9. Composition of Dissolution
Medium
Table 4: composition of FeSSIF
FeSSIF pH 5.0
Sodium taurocholate 15 mM
lecithin 3.75 mM
Acetic acid 8.65gm
NaCl 11.874gm
NaOH 4.04gm
Distilled water q.s. to 1L
pH 5.0

10. In vitro Glimepiride release
study
 Preparation of standard curve:
SL No. Concentration Absorbance
1 0 0
2 5 0.37
3 10 0.69
4 15 1.03
5 20 1.36
6 25 1.61

11. In vitro Glimepiride release
study
 Graphical representation of comparative drug release profile
of generic drug with innovator brand.
 Zero order plot:
Fig: zero order plot for release profiles Fig: zero order plot for release profiles
Of Generic and Amaryl ,Diaryl & Secrin in fassif
Of Generic and Amaryl ,Diaryl & Secrin in fassgf

12. In vitro Glimepiride release
study
Fig: zero order plot for release profiles of Generic and Amaryl in fessgf Fig:zeroorderplotforreleaseprofilesofGenericandAmaryl,Diaryl&Secrininfessif

13. In vitro Glimepiride release
study
1st Order Plot:
Fig: first order plot for release profiles of Generic and Amaryl,Diaryl & Secrin in fassgf

14. In vitro Glimepiride release
study
Fig: first order plot for release profiles of Generic and Amaryl,Diaryl, Secrin in fessgf

15. In vitro Glimepiride release
study
 Higuchi Plot:
Fig:HiguchiplotforreleaseprofilesofGenericandAmaryl,Diaryl,Secrininfassgf Fig:HiguchiplotforreleaseprofilesofGenericandAmaryl,Diaryl,Secrininfassif

16. In vitro Glimepiride release
study
Fig:HiguchiplotforreleaseprofilesofGenericandAmaryl,Diaryl,Secrininfessgf Fig:HiguchiplotforreleaseprofilesofGenericandAmaryl,Diaryl,Secrininfessif

17. Comparison of Dissolution
Data

18. Comparison of Dissolution Data
Table: Comparison of difference factor and similarity factor in FaSSGF
Brand f1 f2
Diaryl 14.88 66253
Secrin 3.86 67.74
Table: Comparison of difference factor and similarity factor in FaSSIF
Brand f1 f2
Diaryl 3.23 73.51
Secrin 6.13 66.33
Table: Comparison of difference factor and similarity factor in FeSSGF
Brand f1 f2
Diaryl 11.78 65.44
Secrin 2.98 80.68
Table: Comparison of difference factor and similarity factor in FeSSIF
Brand f1 f2
Diaryl 6.97 71.68
Secrin 8.43 63.96

19. Conclusion
 Food induced solubility of poor soluble drug glimepiride was
tested in four biorelevant medium as in vitro simulation of
gastrointestinal conditions. Glimepiride was observed to be
best soluble in the intestinal medium than the gastric medium.
While the highest dissolution was achieved in the intestine at
fasted state, food seemed to have reduced the dissolution rate
of the drug both in the intestine and in the stomach. From the
difference factor and the similarity factor it could be deduced
that the two generic brands were equivalent.
 By using biorelevant medium it was possible to predict the
most empirical dissolution rate for the glimepiride brads and
thus it was possible to predict the bioequivalence of the
glimepiride brands.

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