Effect of Hydroxypropyl Methylcellulose and Ethyl Cellulose Content on Release Profile and Kinetics of Diltiazem HCl from Matrices

R Enayatifard,M Saeedi,Y H Tabatabaee,J Akbari

doi:10.4314/tjpr.v8i5.48086

Abstract

Purpose: To develop a oral controlled matrix drug delivery system for a highly water soluble drug, diltiazem HCl, and investigate its drug release mechanism. Method: Diltiazem HCl was chosen because of its high water solubility. Tablets containing the drug were prepared by direct compression method using different matrix ratios of ethyl cellulose (EC) andhydroxypropyl methylcellulose (HPMC). The formulations were evaluated in vitro for their dissolution characteristics over a period of 8 h. Drug release was analysed according to various release kineticmodels. Results: The results showed that these polymers slowed down the release of diltiazem HCl from the matrices. In the presence of EC, increasing the concentration of HPMC decreased the release rate ofdiltiazem. Furthermore, incorporation of EC in tablets with HPMC as the matrix was found to control drug release. Kinetic analysis showed that drug release from three of the formulations was adequatelydescribed by zero order model. Conclusion: The formulations developed could potentially be used for controlled delivery of highlysoluble drugs such as diltiazem HCl.

Highlights

Oral ingestion has long been the most convenient and commonly employed route of drug delivery due to ease of administration, high patient compliance, least sterility constraints and flexibility in the design of dosage form
Despite studies in the 1960s describing their uses [2,3], their characterization and performance have been more extensively quantified only recently. Their properties as gelling agents are very important in the formulation because they are responsible for the formation, by hydration, of a diffusion and erosion-resistant gel layer which is able to control drug release [4]
The in vitro drug release data obtained over a period of 8 h indicate that for F1, F2 and F3 formulations, the release rate decreased as the concentration of hydroxylpropyl methylcellulose (HPMC) increased

Summary

INTRODUCTION

Oral ingestion has long been the most convenient and commonly employed route of drug delivery due to ease of administration, high patient compliance, least sterility constraints and flexibility in the design of dosage form. Designing controlled release drug delivery systems for providing 12 or 24 h zero order release kinetics, especially for highly water-soluble agents, is often difficult and unsuccessful. For drugs with high water solubility, hydrophobic polymers are suitable, along with a hydrophilic matrix, for developing sustained release dosage forms. Diltiazem HCl, an orally active calcium channel blocking agent, is used in the treatment of angina pectoris, hypertension and arrhythmia It is highly water-soluble drug, and is rapidly and almost completely (60-70%) absorbed from GIT following oral administration, but undergoes extensive hepatic metabolism. A one–way ANOVA with a Tukey’s post hoc test was used to analyze the dissolution data obtained for each batch of formulation in order to compare the rate of drug release from the matrix tablets.

RESULTS

DISCUSSION

CONCLUSION