Design and evaluation of innovative bilayer tablet of Gliclazide and Sitagliptin for the management of type II diabetes mellitus 

 Primary Author: K. Reeta Vijaya Rani¹

M. Suba², Mullaicharam Bhupathyraaj³, Muralikrishnan Dhanasekaran⁴, Kiruba Mohandoss ⁵

1. Department of Pharmaceutics, Surya School of Pharmacy, Surya Group of Institutions, Vikravandi, Villupuram – 605 652, Tamilnadu, India.

2. Dr. Kalam College of Pharmacy, Periyanayagipuram, Aavanam, Thanjavur (Dt), Tamil Nadu, India.

3. College of Pharmacy, National University of Science and Technology, Muscat, Oman.

4. Department of Drug Discovery and Development, Harrison College of Pharmacy, Auburn University, Auburn, AL, 36849, USA.

5. Sri Ramachandra Institute of Higher Education and Research, Chennai - 600 116, Tamil Nadu, India.

ABSTRACT:

AIM & OBJECTIVE: Diabetes Mellitus is a metabolic disorder where the major clinical problem is hyperglycemia.  However, other complications and comorbidities are associated with diabetes mellitus, such as stroke, cardiac failure, loss of vision, renal damage, and neurological problems.  Gliclazide and Sitagliptin are well-accepted and globally used therapeutic anti-hyperglycemic medications.  Gliclazide (Sulfonylureas) Subsequently, a scientific endeavor was designed to overcome glucose intolerance and maintain blood glucose at the optimum level using a novel technology, “Bilayer tablet compression”.

METHODOLOGY: Gliclazide Sustained Release (SR) tablets were prepared using polymer HPMC in different viscosity grades with different ratios of drug and polymer (1:1, 1:1.5. 1:2). Similarly, Sitagliptin Immediate Release (IR) tablets were prepared using various super disintegrants with different percentages.  Based on pre-formulation and the in vitro release characteristics, four formulations were selected as the optimal formulations for the current study.  The selected SR & IR formulations were combined and compressed as bilayer tablets and subjected to in vitro release studies and drug release kinetics.

RESULTS AND DISCUSSION: The novel Bilayer tablet compression showed an immediate release of 100.04% within 60 minutes and a sustained release of 104.98% at 24 hours.  The release kinetics data have been best fitted for zero-order and korsmeyar peppas; the values are r2=0.999 and n= 0.812.  It further showed that it follows a non-fickian transport mechanism.

CONCLUSION: The present work has achieved the rapid drug release of Sitagliptin to give immediate anti-hyperglycemic pharmacodynamic action combined with the sustained release of Gliclazide to achieve a prolonged pharmacological effect by continuously releasing medication over an extended period of 24 hours after administration of a single dose.  The current novel formulation synergistically exerts its pharmacodynamic potential by enhancing insulin secretion through activating beta-cell sulphonylurea receptors, stimulating intracellular calcium transport, specifically improving the abnormal first and second-phase insulin release, and preserving stimulated circulating plasma levels of incretin.  Additionally, insulin secretion is stimulated under hyperglycemic conditions, and glucagon secretion is suppressed.  Thus, our new and novel pharmaceutical dosage form can significantly reduce hyperglycemia without significant adverse effects and improve the quality of life of diabetic mellitus patients worldwide.

KEY WORDS:Gliclazide, Sitagliptin, TypeIIdiabetesmellitus, Bilayer tablet