Formulation and optimization for DPP-4 inhibitor nanomicelles using response surface methodology

Abstract

Objective: Dipeptidyl peptidase-4 (DPP-4) inhibitors are the oral antidiabetics that inhibits the enzyme DPP-4. The main aim of study was to formulate, statistically optimize and characterize the polymeric nanomicellar (PNM) formulation of DPP-4 inhibitor (sitagliptin) using natural polymer and a nonionic surfactant.

Method: Response surface methodology (RSM) an experimental design was applied for optimization of nanomicelles using full central composite design. Drug and polymer concentration are independent variables (each at two factor three level) whereas drug loading (% DL) (R1), entrapment efficiency (% EE) (R2) and % drug release (R3) were identified as dependent variables. The polymeric nanomicelles were prepared by direct dissolution method and characterized for surface morphology, particle size, polydispersity index, zeta potential, entrapment efficiency, drug loading, and % drug release.

Results: The optimized formulation of sitagliptin loaded polymeric nanomicelles (PNM 10) was found to be clear, homogenous nanomiceller solution with round spherical structures with a low poly dispersity index of 0.564. PNM 10 has particle size of 368.2 nm. PNM 10 showed drug loading of 38.67 ± 0.23%, entrapment efficiency of 79.67 ± 0.54% and % drug release (R3) of 82.34 ± 0.78%.

Conclusion: Design-Expert (DOE) version 11.0.5.0 software (Stat-Ease Inc, USA) was used for statistically optimization of formulations. PNM 10 was considered best optimized formulation and highly stable for prolonged use and found to be safe for application. Thus this can be a futuristic approach for developing nanomicelles, which can minimize the possible side effects of drug.

Keywords:

• DPP-4 inhibitors
• central composite design
• response surface methodology
• polymeric nanomicelles
• sitagliptin

Acknowledgements

All authors have contributed significantly in the preparation of the manuscript and are in agreement with the content of the manuscript and agree to submission to Drug Development and Industrial Pharmacy, Taylor & Francis. The authors express gratitude to DIT University, Faculty of Pharmacy.

Disclosure statement

The authors declare that there is no conflict of interest that could be prescribed as prejudging the impartiality of the review. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.