Development and Characterization of Mucoadhesive Microcapsules of Nateglinide: Ionic Orifice Gelation Technique

Abstract

Type-2 diabetes is a metabolic disorder where the body is unable to automatically regulate blood glucose levels, resulting in hyperglycemia because the pancreatic β-cell does not produce enough insulin. This produces the classical symptoms of Polyuria (frequent urination), polydipsia (increased thirst) and polyphagia (increased hunger). Nateglinide is a meglitinide short-acting non-sulfonylurea, pancreatic, beta-cell-selective, KATP potassium channel blocker that improves overall glycemic control in type-2 diabetes. Nateglinide binds rapidly to the sulfonylurea SUR1 receptor with rapid association and dissociation gives nateglinide a unique "fast on-fast off" effect. Nateglinide has short biological half-life of 1.5-2.5 h and therefore a sustained release medication is required to get prolonged effect and to reduce fluctuations in drug plasma concentration levels. Microencapsulation is an accepted process used to achieve controlled release and drug targeting for many years. Mucoadhesion has been a topic of interest in the design of drug delivery systems to prolong its intestinal residence time. Mucoadhesion facilitates the intimate contact of the dosage form with the underlying absorption surface for improved bioavailability of drugs. Nateglinide microcapsules were prepared employing SA (sodium alginate) as the coat material in combination with some mucoadhesive polymers such as (sodium carboxy methylcellulose) Sod. CMC and (methyl cellulose) MC (drug:SA:polymer at ratios 2:2:1, 2:3:1 and 2:4:1) following orifice-ionic gelation technique. Infrared (IR) spectroscopy, differential scanning calorimetry and X-ray diffraction studies proved the compositions were compatible without any interaction between the drug and excepients. The prepared microcapsules were evaluated for various physical and release parameters. The resulted microcapsules were found to be discrete and spherical in scanning electron microscopy studies and free flowing in rheological studies. The size of microcapsules was found to be around 756.54 ± 19.276 μm to 797.12 ± 14.761 μm. The microencapsulation efficiency and swelling index was found to be higher in Sod. CMC than in MC containing formulations. The microcapsules with MC exhibited good mucoadhesive property in the in vitro wash-off test. In vitro drug release studies of nateglinide microcapsules were carried out up to 24 h and they followed zero-order release kinetics with Super case II mechanism. The drug release from the microcapsules was sustained over a prolonged period with greater retardation in drug:SA:Sod.CMC (2:4:1) containing microcapsules and this proved to be the best formulation.