In vitro evaluation of pectin–HPMC compression coated 5-aminosalicylic acid tablets for colonic delivery

Abstract

In this study, we report pectin–HPMC compression coated core tablets of 5-aminosalicylic acid (5-ASA) for colonic delivery. Each 100 mg core tablet contained 5-ASA and was compression coated at 20 kN or 30 kN using 100% pectin, 80% pectin–20% HPMC, or 60% pectin–40% HPMC, at two different coat weights as 400 or 500 mg. Drug dissolution/system erosion/degradation studies were carried out in pH 1.2 and 6.8 buffers using a pectinolytic enzyme. The system was designed based on the gastrointestinal transit time concept, under the assumption of colon arrival times of 6 h. It was found that pectin alone was not sufficient to protect the core tablets and HPMC addition was required to control the solubility of pectin. The optimum HPMC concentration was 20% and such system would protect the cores up to 6 h that corresponded to 25–35% erosion and after that under the influence of pectinase the system would degrade faster and delivering 5-ASA to the colon. The pectin–HPMC envelope was found to be a promising drug delivery system for those drugs to be delivered to the colon.

Introduction

Colonic delivery of drugs has attracted a lot of attention and many different approaches were discussed in the literature. Kopecek et al. [1] reported new hydrogels with azoaromatic crosslinks that were sensitive to azoreductases for colonic delivery of peptides such as insulin. Ashford et al. [2] studied a pH dependent system using Eudragit S to deliver salicylic acid to the colon and concluded that pH dependent systems may not be the best approach. Ashford et al. [3] reported the use of compression coated pectin on core tablets for colonic delivery and they reported that pectin USP was the correct choice among the other pectin grades and a minimum coat weight of 700 mg would be required for a dosage form to reach the colon based on mouth to colon transit time concept. Another study concentrating on azo polymers was reported by Mooter et al. [4] and it was concluded that the degree of swelling of hydrogels affected the azo bonds. Gazzaniga et al. [5] reported the use of HPMC either by press coat or spray coat techniques applied to active cores for colonic delivery based on the gastro-intestinal (GI) transit time concept. According to Steed et al. [6] beclomethasone could be delivered to the colon in a HPMC matrix coated with an enteric polymer. Calcium pectinate was suggested by Rubinstein and Radai [7] for colonic delivery. Amylose coated 5-aminosalicylic acid (5-ASA) cores was reported by Milojevic et al. [8] they combined water insoluble polymers to the coat to control drug release. A pectin–ethylcellulose combination as a coating material was reported by Wakerly et al. [9]. Sriamornsak [10] reported calcium pectinate gel beads for oral delivery of proteins to the colon. Macleod et al. [11] reported mixed films of pectin chitosan and HPMC, Turkoglu et al. [12] suggested a pectin–HPMC compression coat system for colonic drug delivery. Lauroyldextran and crosslinked galactomannan were reported as new coating materials for site-specific drug delivery by Hirsch et al. [13].

The purpose of this study was to develop and evaluate a drug delivery system in vitro based on a compression coated tablet containing 5-ASA as the core and a pectin HPMC mixture as the coat layer based on the GI transit time concept. The main reason for selecting pectin was its biodegradation in the colon by colonic flora. On the other hand, high molecular weight HPMC increases the mechanical strength of the tablet wall around a drug core during its transportation in the gastro-intestinal tract. Hence, it was our hypothesis that with the positive contribution of HPMC, pectin would be a good candidate for designing a colonic delivery system.