Fabrication and Characterization of Gliclazide Nanocrystals.

Nagaraju Ravouru,Saritha Damineni,Rajeswari Surya Anusha Venna,Subhash Chandra Bose Penjuri,Venkata Subbaiah Kotakadi,Srikanth Reddy Poreddy

doi:10.15171/apb.2018.049

Abstract

Purpose: The main aim of the present investigation was to enhance the solubility of poorly soluble Gliclazide by nanocrystallization.Methods: In present investigation gliclazide nanocrystals were prepared by sonoprecipitation using Pluronic F68, Poly Vinyl Alcohol (PVA), Poly ethylene Glycol 6000 (PEG), Poly Vinyl Pyrrolidine (PVP K30) and Sodium Lauryl Sulphate (SLS) as stabilizers. Fourier Transform Infrared Spectroscopic study (FTIR), Differential Scanning Calorimetry (DSC) and X ray diffraction (XRD) studies were conducted to study the drug interactions. Size and zeta potential of the nanocrystals were evaluated. In vitro and in vivo studies of nanocrystals were conducted in comparison to pure gliclazide.Results: The Gliclazide nanocrystals (GN) showed mean particle size of 131±7.7 nm with a zeta potential of -26.6 mV. Stable nanocrystals were formed with 0.5% of PEG 6000. FTIR, DSC and XRD studies of nanocrystals showed absence of interactions and polymorphism. SEM photographs showed a change in morphology of crystals from rod to irregular shape. There is an increase in the saturation solubility and the percentage drug release from formulation GN5 (Optimized Gliclazide Nanocrystals) was found to be 98.5 in 15 min. In the in vivo study, GN5 nanocrystals have reduced the blood glucose level to 296.4±4.26 mg/dl in 12 hr. The nanocrystals showed lower tmax and higher Cmax values as compared to pure gliclazide.Conclusion: The prepared nanocrystals of gliclazide were stable without any drug polymer interactions. Increase in the dissolution of nanocrystals compared to pure gliclazide and significant reduction in blood glucose level in vivo indicated better bioavailability of the nanocrystals. Therefore, it is concluded that nanocrystal technology can be a promising tool to improve solubility and hence dissolution of a hydrophobic drug.

Highlights

According to Biopharmaceutical classification system drugs are categorized into 4 classes, each class having its own rate limiting factor affecting its bioavailability
In present investigation gliclazide nanocrystals were prepared by sonoprecipitation using Pluronic F68, Poly Vinyl Alcohol (PVA), Poly ethylene Glycol 6000 (PEG), Poly Vinyl Pyrrolidine (PVP K30) and Sodium Lauryl Sulphate (SLS) as stabilizers
Increase in the dissolution of nanocrystals compared to pure gliclazide and significant reduction in blood glucose level in vivo indicated better bioavailability of the nanocrystals

Summary

Introduction

According to Biopharmaceutical classification system drugs are categorized into 4 classes, each class having its own rate limiting factor affecting its bioavailability. At present most of the drugs (approximately 70%) in the development pipelines belongs to class II and have rate of dissolution as limiting factor for the absorption due to poor solubility.[1] Though different approaches are available to improve the rate of dissolution, drug nanocrystals are preferred over the other. Gliclazide is a BCS class II drug having low

Methods

Results

Conclusion