Design, In Vitro Evaluation and Release Rate Kinetics of Matrix Type Sustained Release Tablet Containing Aceclofenac

摘要

Enteric coated aceclofenac matrix tablets were formulated as sustained release tablets employing hydroxypropyl methylcellulose polymer and the sustained release behavior of the fabricated tablets were investigated. Sustained release matrix tablets containing 200 mg aceclofenac were developed using different drug polymer ratios of hydroxypropyl methylcellulose. Tablets were prepared by wet granulation technique. Formulation was optimized on the basis of acceptable tablet properties and in vitro drug release. The resulting formulations produced monolithic tablets with optimum hardness, uniform thickness, consistent weight uniformity and low friability. Aceclofenac release from tablets was extended from 16 to 24 h from formulated batches. The results of dissolution studies indicated that formulation F-V (drug to polymer 1:0.470), the most successful of the study, exhibited drug release pattern very close to theoretical release profile. Applying kinetic equation models to F-V batch it was found to be followed Higuchi model, as the plots showed high linearity, with correlation coefficient (R2) value 0.9911.Therefore, the formulation F-V tablets showed diffusion dominated drug release. The accelerated stability study showed that the shelf life 40 months (batch F-V) and promising drug storage results. Introduction Aceclofenac, a phenylacetic acid derivative, is a non-steroidal anti-inflammatory drug (NSAID) related to diclofenac. It is used in the management of osteoarthritis, rheumatoid arthritis and alkylosing spondylitis (1). Through its analgesic and anti-inflammatory properties, aceclofenac provides symptomatic relief in a variety of painful conditions. Aceclofenac is well tolerated, with most adverse effects being minor and reversible, affecting mainly gastrointestinal system (2). It is well absorbed from gastrointestinal tract and peak plasma concentrations (Cmax) are reached 1-3 h after oral dose. The short biological half life (approximately 4.3 h) and the need for long duration favour development of a sustained release formulation. Sustained release tablets can offer advantages like limiting fluctuation within the therapeutic range, decreasing dosage frequency and improving patient compliance.The simplest way to retard drug release is to disperse it in a solid matrix. The matrix system is commonly used for manufacturing sustained release dosage forms especially tablets because it makes such manufacturing easy. Hydrophilic matrices are an interesting option when formulating an oral sustained release (SR) of a drug. The dosage release properties of matrix devices may be dependent upon the solubility of the drug in the polymer matrix or, in case of porous matrices, the solubility in the sink solution within the particle’s pore network (3). Hydroxypropyl methylcellulose (HPMC) is the dominant hydrophilic vehicle used for the preparation of oral controlled drug delivery systems (4). Numerous studies have been reported in literature investigating the HPMC matrices to control the release of a variety of drugs from matrices and trying to predict drug release kinetic models (5-9). According to most of these models, diffusion is thought to occur in release of drugs and anomalous release due to effect of excipients in matrices. One of the common complaints of oral NSAID including aceclofenac is gastric irritation associated with their use. Therefore enteric coated aceclofenac tablets are interesting option to circumvent this problem of GI irritation.The objective of the study was to prepare enteric coated sustained release aceclofenac tablets using HPMC matrix, to examine the in vitro release characteristics, to predict the release behavior of aceclofenac from the matrix and to elucidate shelf life of the fabricated formulation. In order to elucidate release kinetics it is necessary to fit drug release data into a suitable model. The commonly adopted models for understanding the release of drugs from hydrophilic matrices are first-ord