INTRODUCTION TO GLICLAZIDE TABLETS

Gliclazide is an oral hypoglycemic (anti-diabetic drug) and is classified as a sulfonylurea. It is marketed as Glizid, Glyloc and Reclide in India

and Diamicron in Canada and Australia. In the Philippines, Servier markets it as Diamicron MR, like in most countries across the world. Many generic equivalents are also available e.g. Glubitor-OD, Clizid. It is not marketed in the United States. A modified-release formulation is also marketed. Its classification has been ambiguous, as literature uses it as both a firstgeneration [1] and second-generation sulfonylurea. Gliclazide was proven to protect human pancreatic beta-cells from hyperglycemia-induced apoptosis. It was also shown to have an antiatherogenic effect (preventing accumultaion of fat in arteries) in type 2 diabetes.

CHEMICAL PROPERTIES

N-(hexahydrocyclopenta[c]pyrrol-2(1H)-ylcarbamoyl)-4methylbenzenesulfonamide

FORM AND COMPOSITION

Each immediate-release tablet contains 80 mg. Modified release formulations contain 30 mg and 60 mg of gliclazide.

INDICATION
Gliclazide is used for control of hyperglycemia in gliclazide-responsive diabetes mellitus of stable, mild, non-ketosis prone, type 2 diabetes. It is used when diabetes cannot be controlled by proper dietary management and exercise or when insulin therapy is not appropriate.

MODE OF ACTION
Gliclazide selectively binds to sulfonylurea receptors (SUR-1) on the surface of the pancreatic beta-cells. It was shown to provide cardiovascular protection as it does not bind to sulfonylurea receptors (SUR-2A) in the heart.[5] This binding effectively closes the K+ ion channels. This decreases the efflux of potassium from the cell which leads to the depolarization of the cell. This causes voltage dependent Ca++ ion channels to open increasing the Ca++ influx. The calcium can then bind to and activate calmodulin which in turn leads to exocystosis of insulin vesicles leading to insulin release.

DOSAGE
The dosage for the 80 mg formulation is 40 to 320 mg daily in two divided doses, while the 30 mg and 60 mg modified release formulation may be given at a dose of 30 to 120 mg once daily at breakfast.

PROPERTIES

Hypoglycemic sulfonylurea, restoring first peak of insulin secretion, increasing insulin sensitivity.

Glycemia-independent hemovascular effects, antioxidant effect. No active circulating metabolites.

CONTRAINDICATIONS

Type 1 diabetes Hypersensitivity to sulfonylureas Severe renal or hepatic failure

Pregnancy and lactation Miconazole coprescription

METABOLISM
Gliclazide undergoes extensive metabolism to several inactive metabolites in humans, mainly methylhydroxygliclazide and carboxygliclazide. CYP2C9 is involved in the formation of hydroxygliclazde in human liver microsomes and in a panel of recombinant human P450sin vitro. But the pharmacokinetics of gliclazide MR are affected mainly by CYP2C19 genetic polymorphism instead of CYP2C9 genetic polymorphism.

INTERACTIONS
Hyperglycemic action may be caused by danazol, chlorpromazine, -blockers, glucocorticoids, progestogens, or -2 agonists. Its hypoglycemic action may be potentiated by phenylbutazone, alcohol, fluconazole, and

possibly ACE inhibitors. It has been found that rifampin increases gliclazide metabolism in humans in vivo.

ADVERSE EFFECTS

Hypoglycemia - while it was proven to have the same efficacy as glimepiride, one of the newer sulfonylureas, the European GUIDE study has shown that it has approximately 50% fewer confirmed hypoglycaemic episodes in comparison with glimepiride.

Gastrointestinal disturbance (reported) Skin reactions (rare) Hematological disorders (rare) Hepatic enzyme rises (exceptional)

OVERDOSAGE
Gliclazide overdose may cause severe hypoglycemia, requiring urgent administration of glucose by IV and monitoring

SIDE EFFECTS: Nausea, stomach upset or diarrhea may occur as your body adjusts to the medication. If any of these effects continue or become bothersome, inform your doctor. Notify your doctor if you develop a skinrash, itching, easy bruising or bleeding, fever, weakness, trembling or chills while taking this medication. This medication may cause low blood sugar (hypoglycemia) which manifests as dizziness, weakness, drowsiness,headache, sweating, nervousness, shaking, tingling of the hands or feet, hunger, fast heartbeat. Should these symptoms occur, drink a glass of orange juice or nondiet soda or eat a piece of candy to raise your blood sugar level quickly. Report the incident to your doctor. To help prevent low blood sugar, eat meals on a regular schedule and do not skip meals. Symptoms of high blood sugar (hyperglycemia) include confusion, drowsiness, flushing, rapid breathing or fruity breath odor. Notify your doctor if you experience any of these symptoms. If you notice other effects not listed above, contact your doctor or pharmacist.

PHYSICAL PROPERTIES OF THE FORMULATED TABLETS

The physical appearance, tablet thickness, diameter, hardness, friability and weight variation of all tablets were found to be satisfactory and reproducible as observed from the table 3. Thickness was within the range of 3.20 to 3.50, diameter within the range of 9.99 to 10.02, hardness was within the range of 8.1 to 11.3. Friability value for all the tablets was less than 0.5. Weight variation of the tablets was also within acceptable range.

Table: Physical Properties of the Gliclazide Tablets

CONCLUSION
From the investigation it was found that tablets prepared by direct compression offered maximum drug release in all polymeric contents than those were prepared by wet granulation technique. It was also observed that Higher polymer content in the matrix decreased the rate of the drug due to increased tortuosity and decreased porosity and at lower polymeric level the rate of drug release was elevated. The tablets showed good tabletting properties which may also be taken in account to evaluate the polymeric content and granulation process. Thus a controlled plasma level profile of drug can be obtained by judicious selection of polymeric content and granulation process in matrix system.

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