Dissolution rate enhancement of repaglinide by solid dispersion

Xiao-Dong Yang,Da-Hong Gao,Hai-Li Ma,Yan-Juan Tian,Wan-Sen Li,Cheng-Gong Liu

doi:10.4314/tjpr.v15i6.2

Abstract

Purpose : To enhance the solubility and dissolution rate of the antidiabetic drug repaglinide by solid dispersion (SD) technique Method : The solid dispersion of repaglinide was prepared by solvent evaporation method using the hydrophilic carrier, polyethylene glycol 4000 (PEG 4000) in three drug:PEG 4000 ratios (1:1, 1:3, 1:5). For comparison, physical mixtures of repaglinide and PEG 4000 in the same ratios were also prepared. The formulations were characterized by Fourier transformed infrared spectroscopy (FTIR), x-ray diffractometry (XRD) and differential scanning colorimetry (DSC). Phase solubility study of pure repaglinide, physical mixture and solid dispersion was performed in distilled water. Dissolution studies were carried out in pH 7.4 phosphate buffer. Results : DSC and XRD results indicate that repaglinide exists in amorphous form in solid dispersion. FT-IR analysis demonstrated the presence of intermolecular hydrogen bonding between repaglinide and PEG 4000 in the solid dispersion. The solubility of pure repaglinide was enhanced from 22.5± 5.0 to 235.5± 5.0 μg/mL in distilled water at 37 0C. Rapid burst release (80 - 86 %) from the solid dispersion formulations was observed within 15 min. Conclusion : The solubility and dissolution rate of repaglinide are enhanced by formulating SDs of repaglinide with PEG 4000. This will likely lead to increase in bioavailability which would be beneficial for better glucose control in diabetic patients. Keywords : Diabetes, Solid dispersion, Repaglinide, Solubility, Dissolution, Burst release

Highlights

The oral bioavailability of a pharmaceutically active ingredient depends on its water solubility and dissolution rate
Pure RPG and its physical mixture with Polyethylene glycol (PEG) 4000 exhibited an endothermic peak at around 135 °C, which was consistent with the melting point of repaglinide
The former resulted from the amorphous nature of the polymer, and the later revealed no crystallinity of repaglinide existed in solid dispersion, indicating that repaglinide might be in an amorphous form

Summary

Introduction

The oral bioavailability of a pharmaceutically active ingredient depends on its water solubility and dissolution rate. Solid dispersion (SD) is one of the most widely used techniques to improve solubility as well as dissolution rate of poorly water soluble drugs This method involves a dispersion of one or more active ingredients in an inner carrier or matrix in solid state prepared by melting, dissolution in solvent or melting solvent method [4]. The drug and carrier are dissolved in a mutual organic solvent followed by solvent evaporation, whereas in fusion method, drug-carrier mixtures are prepared by co-melting and cooling. In both methods, a suitable carrier needs to be selected in order to achieve enhanced solubility [5]. Polyethylene glycol (PEG) and polyvinylpyrrolidone (PVP) are amongst the most frequently investigated hydrophilic polymeric carriers.SD using suitable carrier, changes the micro-environment of the drug particles, reduces the drug particle size thereby increasing dissolution, solubility and changes biopharmaceutical properties [6]

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Conclusion