A study of enteric-coated liquid-filled hard gelatin capsules with biphasic release characteristics

Abstract

Studies were carried out using enteric-coated, liquid-filled hard gelatin capsules with biphasic rapid and sustained release characteristics, containing 80 mg of propranolol in a novel HALO ™ drug delivery formulation designed to avoid hepatic first-pass metabolism. The disintegration at pH 1.0 of HALO ™-propranolol capsules, coated with different levels (3–12 mg/cm 2) of enteric polymer (methacrylic acid copolymer, type A USP/NF) was visually assessed using the disintegration test for enteric-coated capsules described in the BP 1988. Quantification of propranolol release, at pH 1.0, from enteric-coated capsules was carried out using a dissolution procedure based on the USP XXII method. The results of the study showed that significant release of propranolol (> 10%) could take place at low coating levels (3 mg/cm 2) without visible breakdown of the enteric coat. In a further study, enteric-coated HALO ™-propranolol capsules coated with 4 mg/cm 2 of enteric polymer were stored under a variety of conditions for up to 18 months. Dissolution and disintegration studies showed that under conditions of low temperature storage (4°C) HALO ™-propranolol capsules released significant amounts ( > 10%) of propranolol at pH 1.0 without visible breakdown of the enteric coat. Dissolution studies carried out at pH 6.8 following acid challenge demonstrated that inadequate enteric protection greatly affected the subsequent sustained-release dissolution profile of HALO ™-propranolol capsules. The present investigation demonstrates the importance of ensuring a sufficient enteric-coating level for oral dosage vehicles to maintain post gastric dissolution characteristics and illustrates the need for a reliable means of assessing enteric coat performance in vitro.