Design of bilayer tablets using modified Dioscorea starches as novel excipients for immediate and sustained release of aceclofenac sodium.

Adenike Okunlola

doi:10.3389/fphar.2014.00294

Abstract

Bilayer tablets of aceclofenac sodium were developed using carboxymethylated white yam (Dioscorea rotundata) starch (CWY) for a fast release layer (2.5, 5.0, and 7.5% w/w), and acid-hydrolyzed bitter yam (Dioscorea dumetorum) starch (ABY) for a sustaining layer (27% w/w). Sodium starch glycolate (SSG) and hydroxypropyl methyl cellulose (HPMC) were used as standards. The starches were characterized using Fourier Transform Infrared spectroscopy (FT-IR), particle size, swelling power, densities and flow analyses. Mechanical properties of the tablets were evaluated using crushing strength and friability while release properties were evaluated using disintegration and dissolution times. Distinctive fingerprint differences between the native and modified starches were revealed by FT-IR. Carboxymethylation produced starches of significantly (p < 0.05) higher swelling and flow properties while acid-modification produced starches of higher compressibility. Bilayer tablets containing ABY had significantly higher crushing strength and lower friability values (p < 0.05) than those containing HPMC. Crushing strength increased while friability values decreased with increase in CWY. Generally tablets containing the modified Dioscorea starches gave faster (p < 0.05) disintegration times and produced an initial burst release to provide the loading dose of the drug from the immediate-release layer followed by sustained release (300 ± 7.56–450 ± 11.55 min). The correlation coefficient (R2) and chi-square (χ2) test were employed as error analysis methods to determine the best-fitting drug release kinetic equations. In vitro dissolution kinetics generally followed the Higuchi and Hixson-Crowell models via a non-Fickian diffusion-controlled release. Carboxymethylated white yam starch and acid-modified bitter yam starch could serve as cheaper alternative excipients in bilayer tablet formulations for immediate and sustained release of drugs respectively, particularly where high mechanical strength is required.

Highlights

The cost of developing a new drug molecule is usually high; efforts are directed at the development of new dosage forms for existing drugs with improved safety and efficacy as well as reduced dosing frequency and cost
Bi-layer tablets are suitable for formulating sustained release tablet in which one layer is formulated to obtain immediate release of a drug with the aim of reaching a high serum concentration in a short period of time, while the second layer is designed for sustained release in order to maintain an effective plasma level of the drug for a prolonged period of time
The pharmacokinetic advantage relies on the fact that drug release from fast releasing layer leads to a sudden rise www.frontiersin.org

Summary

Introduction

The cost of developing a new drug molecule is usually high; efforts are directed at the development of new dosage forms for existing drugs with improved safety and efficacy as well as reduced dosing frequency and cost. Conventional monolayer tablets have the limitations of frequent dosing and unpredictable absorption window that may result in wide range of fluctuation in drug concentration in the blood stream and tissues, with subsequent undesirable toxicity and poor therapeutic efficiency (Ansel et al, 2011). These limitations have led Abbreviations: ABY, Acid-modified bitter yam starch; CWY, Carboxymethylated white yam starch. The pharmacokinetic advantage relies on the fact that drug release from fast releasing layer leads to a sudden rise www.frontiersin.org

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