Palmitic Acid-Pluronic F127-Palmitic Acid Penta-Block Copolymer as a Novel Nanocarrier for Oral Delivery of Glipizide

Abstract

Objective: The aim of the present study is to develop nanotechnology-based oral formulations of Glipizide to enhance bioavailability and to eliminate the frequent oral administration of the conventional dosage form. Glipizide is an antidiabetic drug with short biological half-life with limited oral bioavailability. Noval Palmitic acid-Pluronic F127-Palmitic acid (PAF127) pentablock copolymer based prolonged release glipizide nanoparticles (GN) were prepared and screened for in vitro and in vivo studies. Methods: GN was prepared using novel PA-F127 pentablock copolymer by solvent evaporation technique. The prepared nanoparticles were evaluated for particle size, polydispersity index (PDI), zeta potential, entrapment efficiency, percentage yield, drug excipient compatibility using FTIR and DSC analysis, XRD, SEM, In vitro drug release studies, stability studies and in vivo pharmacokinetic studies. Results: The results of FTIR and DSC analysis revealed the absence of drug-excipient interactions. The optimized GN1 has particle size 242.60 ± 4.20 nm, PDI 0.171 ± 0.014 and zeta potential -21.41 ± 0.462 mV. Prepared nanoparticles were spherical in shape and showed semi-amorphous characteristics. In vitro release studies showed 34.43 ± 4.8 % drug was released in first 8 h, 56.11 ± 4.12 % glipizide were released further for 24 h. The GN1 was found to be stable at 5 ± 3 oC up to three months. Pharmacokinetic studies showed that the orally administered GN1 were superior with Cmax 2.35 fold, tmax 1.6 fold, area under the curve (AUC0→∞) 3.3 fold and mean residence time (MRT) 1.2 fold as compared to pure glipizide (p < 0.05). Conclusion: The study concluded that the bioavailability of newly developed GN1 was successfully prolonged and frequent oral administration problem with conventional dosage form can be defeated for diabetes treatment.