Improved dissolution of ofloxacin via solid dispersion

doi:10.1016/S0378-5173(97)00196-8

International Journal of Pharmaceutics

Volume 156, Issue 2, 24 October 1997, Pages 175-180

https://doi.org/10.1016/S0378-5173(97)00196-8 Get rights and content

Abstract

The objective of this study was to improve the dissolution rate of a sparingly water soluble drug, ofloxacin, by solid dispersion systems with urea and mannitol. Differential scanning calorimetry (DSC), powder x-ray diffraction (PXRD) analysis and infrared spectroscopy (IR) were performed to evaluate the physicochemical properties of the prepared solid dispersions. The dissolution rate of ofloxacin was markedly increased in solid dispersion of urea and mannitol. Solubility studies revealed a marked increase in the solubility of ofloxacin with an increase in urea concentration. Mannitol concentration had no effect on the solubility of ofloxacin. The PXRD study revealed that the crystallinity of ofloxacin was decreased as the ratio of drug to carrier was decreased. The results from DSC and IR indicated that there was no interaction between drug and carriers.

Introduction

Ofloxacin (OFX) is a new 4-quinolone derivative with high activity against a wide range of gram-positive and gram-negative bacteria. It is known to exert its antibacterial action by antagonism of the enzyme DNA gyrase (bacterial topoisomerase II), an enzyme that introduces negative supertwists into DNA and separates interlocked DNA molecules. Ofloxacin antagonizes these enzymetic activities, interfering with DNA replication, segregation of bacterial chromosomes, transcription, and other cellular processes and damaging DNA (Gellert, 1981; Wolfson and Hooper, 1989; Sanders, 1992). Unfortunately, ofloxacin has shown pharmaceutical problems of water solubility. Because of its sparing solubility in water, the dissolution of ofloxacin from its dosage form after oral administration which is an important factor related to its bioavailability, is usually the rate-limiting step in the absorption process (Bates et al., 1967; Kitamori and Iga, 1971).

During the past 30 years, there has been a great deal of interest in using solid dispersions to improve the dissolution rate and the bioavailability of poorly water soluble drugs (Chiou and Riegelman, 1971; Kerc et al., 1993; Jachowicz et al., 1993; Kai et al., 1996; Suzuki et al., 1996). Various water soluble inert materials have shown to improve the dissolution rate and bioavailability of many drugs (Allen et al., 1978; Ghanen et al., 1982; Miralles et al., 1982; Jafari et al., 1988; Law et al., 1992; Simonelli et al., 1994; Yagi et al., 1996).

The present work has been undertaken to develope a solid dispersion of ofloxacin using urea and mannitol in order to improve the dissolution behaviour.

Section snippets

Materials

Ofloxacin (OFX), melting point range 275–277°C was obtained from Daiichi Seiyaku Co. Ltd. (Japan). Urea and mannitol were purchased from Nacalai Tesque Inc. (Japan). All other chemicals were of analytical grade.

Preparation of OFX solid dispersions

Different ratios of OFX and urea or mannitol were accurately weighed. The solid dispersions were prepared by solvent method using the 1:1 mixture of ethanol/chloroform as a solvent. The mixture was evaporated under vacuum on a water bath at 45°C. After complete evaporation, the solid

Crystalline property and thermal behaviour of OFX solid dispersions

The PXRD patterns of OFX solid dispersion are shown in Fig. 1. The physical mixtures of OFX with either urea or mannitol at 1:19 and 1:4 drug to carrier ratios showed both characteristic diffraction peaks of OFX and carrier. In both OFX-urea and OFX-mannitol solid dispersion systems, the intensity of diffraction peaks attributed to OFX gradually decreased with increased carrier content. In the solid dispersion of OFX-urea (1:19), the diffraction peaks of OFX was not observed whereas the

Acknowledgements

This study was supported by the National Research Council of Thailand (NRCT) and the Japan Society for the Promotion of Science (JSPS). We appreciate Daiichi Seiyaku Co. Ltd., Japan, for their kind supply of OFX.

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Improved dissolution of ofloxacin via solid dispersion

Abstract

Introduction

Section snippets

Materials

Preparation of OFX solid dispersions

Crystalline property and thermal behaviour of OFX solid dispersions

Acknowledgements

J. Pharm. Sci.

J. Pharm. Sci.

J. Pharm. Sci.

Int. J. Pharm.

Int. J. Pharm.

Int. J. Pharm.

J. Pharm. Sci.

J. Pharm. Sci.

Solid dispersion of chlothalidone in urea phase diagram and dissolution characteristics

Pharm. Acta. Helv.

Polyethylene glycols and drug release

Drug Dev. Ind. Pharm.