TITLE:
Application of D-Optimal Study Design with Contour Surface Response for Designing Sustained Release Gliclazide Matrix Tablets
AUTHORS:
Chien Nguyen, John Mark Christensen, Thuy Nguyen
KEYWORDS:
Gliclazide, Sustained Release, D-Optimal, Zero-Order, Response Surface, Modified Release
JOURNAL NAME:
Pharmacology & Pharmacy,
Vol.5 No.7,
June
13,
2014
ABSTRACT: An optimized formulation of a sustained release tablet of Gliclazide was
developed. The use of Doptimal design with a polynomial statistical model to
analyze dissolution data reduced the number of laboratory tests required to
obtain an optimal dosage form. The final formulation contained 22 mg of Methocel®E15LV,
16.5 mg Methocel®E15 and 10.0 mg of Dibasic Calcium Phosphate per 30
mg Gliclazide sustained release tablet. Dissolution studies performed on
tablets from 5000 tablet test batches released greater than 90 percent of
loaded drug in eight hours. Drug release from the optimized tablets followed a
pattern more closely similar to zero-order than other mechanisms of drug
release tested. Storage of tablets in accelerated and ambient conditions for 6
and 12 months respectively did not alter any of the physico-chemical properties,
drug release or the drug release rate compared to initial observations and
dissolution data of the prepared tablets. The addition of potassium phosphate
and monosodium phosphate to the tablet reduced the effect pH has on Gliclazide
dissolution compared to the commercially available product.