PREPARATION OF GLIMEPIRIDE MUCOADHESIVE TABLETS BY DIRECT COMPRESSION METHOD AND THEIR IN-VITRO EVALUATION

Objectives: The present investigation is concerned with formulation and evaluation of mucoadhesive buccal tablets containing antidiabetic drug, glimepiride, to circumvent the first pass effect and to improve its bioavailability with reduction in dosing frequency and dose related side effects. Methods: The tablets were prepared by direct compression method. The tablets were tested for weight variation, hardness, surface pH, drug content uniformity, percentage swelling index, bio adhesive strength, exvivo residence time in-vitro drug dissolution study, in-vitro drug release kinetic study, ex-vivo permeation study and stability study. Results: FTIR studies showed no evidence on interactions between drug, polymers, and excipients. The surface pH, bio adhesive strength, ex-vivo residence time and swelling index of formulation was found to be 6.80±0.02, 36.3±0.04g, 325min and 289.8±0.52%, respectively. The formulation containing 4 mg of glimepiride exhibited 6 h sustained drug release i.e. 93.98±0.8% with desired therapeutic concentration. The drug permeation from the formulation was slow and steady and 3.56 mg of glimepiride could permeate through sheep buccal membrane with a flux of 0.27 mg hr -1 cm -2 . The in-vitro release kinetics studies reveal that all formulations fits well with zero order kinetics and followed non-Fickian diffusion mechanism. Conclusion: Hence, it was concluded that the best formulation was suitable for all the evaluation parameters and can be permeated through human buccal mucosa.


INTRODUCTION
Glimepiride is an oral antidiabetic drug which belongs to the sulfonylurea group and usually given as an oral antidiabetic therapy for patients with type 2 diabetes mellitus. Glimepiride acts to lower blood glucose by stimulating the release of insulin from pancreatic β-cells [1,2].
It is used to lower blood sugar in patients with high blood sugar (diabetes) [3,4]. Glimepiride is indicated to treat type 2 diabetes mellitus; its mode of action is to increase insulin production by the pancreas. It is not used for type 1 diabetes because in type 1 diabetes the pancreas is not able to produce insulin. The more common side effects that can occur with glimepiride include low blood sugar (hypoglycemia), trembling or shaking, nervousness or anxiety,

Drug content
The drug content of glimepiride prepared tablet of each batch of the formulation was determined. Approximately around twenty tablets were taken from each batch weighed for the initial weight Percentage Friability of tablets less than 1% is considered acceptable.

Thickness
The thickness of the tablets was determined using a thickness screw gauge. Five tablets from each batch were used and average values were calculated.

Uniformity of weight
To study weight variation, 20 tablets of each formulation were weighed using an electronic balance and the test was performed according to the official method.

Surface pH
The objective of study of surface pH of buccal tablet was to know whether the tablet causes any irritation to mucus membrane of buccal region.
The buccal tablets were allowed to swell at 37 ± 1 °C for 2 hrs in 50 ml phosphate buffer (pH 6.8). The surface pH of swollen buccal tablets was measured by using pH paper [13].

Swelling index study
Swelling study of buccal tablets was done on 1%

Hardness Test
The adequate tablet hardness is necessary requisite for consumer acceptance and handling.
The measured hardness of the tablets of batch was ranged between 4.0±0.09 to 4.6±0.05 Kg/cm 2 . This ensures good handling.

Thickness
The thickness of the tablets was found to be almost uniform in all formulation of batch. The thickness was found to be in the range of 3.26±0.057 to 3.73±0.010 mm (Fig. 2). None of the formulations showed a deviation. Hence, it is concluded that all the formulations complied the thickness test.

Weight Variation
The weight variation test was conducted for each batch of all formulation as per Pharmacopoeia.
The weight variation test for all the formulations complies with the limit (± 10%). The weight variations for formulation were ranged between 149.0±0.20 to 151.1±0.48 mg.

Friability Test
The friability test for all the formulations was done as per the standard procedure. The results of the friability test were ranged between 0.132±0.05 to 0.533±0.04%. The data indicates that the friability was less than 1% in all formulations ensuring that the tablets were mechanically stable.

Surface pH
Surface pH of all the formulations was found to be 6.22±0.08 to 6.87±0.02 (Fig, 2), which is well within the limit of acceptable salivary pH range of 5.6 to 7.

Ex-vivo Residence Time
The ex-vivo residence time is one of the important physical parameter of buccal mucoadhesive tablets. The Ex-vivo residence time was determined by using specially designed dissolution apparatus. The ex-vivo residence time found to be in the range of 230 minutes to 235 minutes (Fig 3).

Swelling Study
The swelling studies were conducted for all formulation. Tablets were hydrated generally by keeping the tablets in contact with water for 1 h to 12 h. The highest hydration (swelling) i.e.

In-vitro Dissolution Studies
In-vitro dissolution studies were designed to carry out in such a way that they simulate invivo conditions. The purpose of in-vitro release study was to provide a fast, easily performed and in-expensive method that correlates with the performance of dosage form in human subjects. These tests indicated that the tablets formed are upto standards and are formulated accurately.
Dissolution and disintegration studies were performed and estimated times are recorded.