THE EFFECT OF BETACYCLODEXTRIN ON THE SOLUBILITY AND DISSOLUTION OF SPIRONOLACTONE USING PHYSICAL MIXING AND CO-EVAPORATION METHODS

Khaled Saleh

doi:10.21608/ajps.2013.7093

Abstract

Spironolactone is a steroidal drug acting as a specific aldosterone antagonist used as potassium sparing diuretic. It shows variable absorption and bioavailability due to its poor solubility. The objective of this study was to investigate the effect of betacyclodextrin (BCD) on the solubility and dissolution of spironolactone using physical mixing and co-evaporation methods. The physical mixtures of different w/w drug/carrier ratios (1:1, 1:2 and 1:3) were prepared by simple mixing. Also co-evaporate systems containing (1:1, 1:2 and 1:3) w/w drug/carrier ratios were prepared. The physicochemical characterization of the systems using differential scanning calorimetry (DSC) and powder X-ray diffraction was carried out to detect the interaction between the drug and the carrier, moreover, quantitative solubility and in-vitro dissolution studies of spironolactone alone and in physical mixtures or co-evaporates were studied in simulated gastric fluid (SGF) of pH 1.2 and in simulated intestinal fluid (SIF) of pH 7.5. The reduction of drug peaks in X-ray diffraction pattern of the co-evaparate and the absence or reduction of drug peaks in DSC profile of the physical mixture and the co-evaporate suggest the transformation of crystalline spironolactone into an amorphous form due to the inclusion complexation with betacyclodextrin. The study showed an increase in the solubility values and an improvement in the dissolution pattern of the drug in case of the physical mixtures and the co-evaporates.

Highlights

Spironolactone is a renal competitive aldosterone antagonist in a class of pharmaceuticals called potassium sparing diuretics
The main technologies to achieve the enhanced oral bioavailability of drugs with poor aqueous solubility include the use of miconization, nanosizing, solid dispersions, cyclodextrins, solid lipid nanoparticles and other colloidal drug delivery systems such as mcroemulsions and self-emulsifying drug delivery systems (Fahr and Liu, 2007; Gomez-Orellana, 2005)
Differential scanning calorimetry: differential scanning calorimetry (DSC) analysis of plain drug, carrier, physical mixture and co-evaporate is shown in Figure (1)

Summary

Introduction

Spironolactone is a renal competitive aldosterone antagonist in a class of pharmaceuticals called potassium sparing diuretics. It is used to treat heart failure, ascites in patients with liver disease, low-renin hypertension and hypokalemia (Rani et al, 2012). It is described as a light, cream-colored to light tan, crystalline powder with a faint to mild mercaptan-like odor, practically insoluble in water, soluble in alcohol and in ethyl acetate, freely soluble in chloroform and in benzene, and slightly soluble in methyl alcohol and fixed oils (USP XXIX, 2006). Spironolactone is absorbed rapidly and bound avidly to protein. It does not show comprehensive therapeutic effect because of its poor solubility and dissolution, which leads to poor bioavailability of the drug (Ahuja et al, 2007). The main technologies to achieve the enhanced oral bioavailability of drugs with poor aqueous solubility include the use of miconization, nanosizing, solid dispersions, cyclodextrins, solid lipid nanoparticles and other colloidal drug delivery systems such as mcroemulsions and self-emulsifying drug delivery systems (Fahr and Liu, 2007; Gomez-Orellana, 2005)

Objectives

Methods

Results