Formulation of novel niosomal repaglinide chewable tablets using coprocessed excipients: in vitro characterization, optimization and enhanced hypoglycemic activity in rats

Abstract

Repaglinide (RPG), a monotherapy insulin secretagogue used to treat diabetes mellitus-type II yet, it suffers from poor water solubility and variable bioavailability (∼ 50%) due to hepatic first pass metabolism. In this study, 2FI I-Optimal statistical design was employed to encapsulate RPG into niosomal formulations using cholesterol,span 60 and peceol^TM. The optimized niosomal formulation (ONF) showed particle size 306.60 ± 84.00 nm, zeta potential −38.60 ± 1.20 mV, polydispersity index 0.48 ± 0.05 and entrapment efficiency 92.00 ± 2.60%. ONF showed > 65% RPG release that lasted for 3.5 h, and significantly higher sustained release compared to Novonorm® tablets after 6 h (p < 0.0001). TEM for ONF showed spherical vesicles with dark core and light-colored lipid bilayer membrane. RPG peaks disappeared in FTIR confirming successful RPG entrapment. To eliminate dysphagia associating conventional oral tablets, chewable tablets loaded with ONF were prepared using coprocessed excipients; Pharmaburst^® 500, F-melt^® and Prosolv^® ODT. Tablets showed friability <1%, hardness 3.9 ± 0.423-4.7 ± 0.410 Kg, thickness 4.1 ± 0.045-4.4 ± 0.017 mm and acceptable weight.All tablets showed robust RPG release at 30 min compared to Novonorm^® tablets. At 6h, chewable tablets containing only Pharmaburst^® 500 and F-melt^® showed sustained and significantly increased RPG release compared to Novonorm^® tablets (p < 0.05). Pharmaburst^® 500 and F-melt^® tablets showed rapid in vivo hypoglycemic effect with 5 and 3.5 fold significant reduction in blood glucose compared to Novonorm^® tablets (p < 0.05) at 30 min. Also, at 6h the same tablets showed 1.5 and 1.3 fold significant extended reduction in blood glucose compared to the same market product (p < 0.05). It could be concluded that chewable tablets loaded with RPG ONF represent promising novel oral drug delivery systems for diabetic patients suffering from dysphagia.

Keywords:

• Diabetes mellitus (type II)
• repaglinide
• niosomes
• coprocessed excipients
• dysphagia
• chewable tablets
• enhanced hypoglycemic activity

Disclosure statement

The authors report there are no competing interests to declare.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.