(W0930-08-52) Influence of Curing Conditions on the Functional Integrity of Aqueous and Solvent-Based Approaches for Enteric Coating

Purpose: Most enteric coatings in the pharmaceutical industry are performed using aqueous polymer dispersion and organic polymer solution. Based on the reported literature, curing modulates the microstructural evolution of enteric films by enhancing polymeric continuity through particle coalescence in aqueous dispersion systems and by facilitating molecular relaxation and chain mobility within solvent cast films. It is imperative to study the effect of curing conditions on drug release from enteric coated formulations, which can then be extended to get a stable product. The purpose of the experiment is to study the effect of curing time, curing temperature on drug release from tablets coated with either aqueous dispersion of Hypromellose Acetate Succinate or solvent based Hypromellose Phthalate without compromising the enteric property.

Methods: To study the impact of curing on drug release, an acid sensitive drug like esomeprazole is selected as a model drug. Esomeprazole 40mg tablets were developed for evaluation, with a total tablet weight of 218mg, 8mm diameter, and 80N tablet hardness. The Esomeprazole tablets were further seal coated with Hypromellose 2910 (6 mPa.s) for 3%w/w weight gain in a perforated coating pan. Further, as a first strategy, enteric coating was performed using an aqueous dispersion of Hypromellose Acetate Succinate (AS-LF) with polymer weight gain of 7%w/w. For aqueous dispersion, triacetin was used as a plasticizer and evaluated at different concentrations. As a second strategy, enteric coating was performed using Hypromellose Phthalate (HP-55) with polymer weight gain of 7%w/w. For solvent based coating, a mixture of isopropyl alcohol and water was used as the solvent system. The enteric coated tablets were subjected to different curing temperatures in an oven for 2h at 40°C, 1h at 50°C, and in a stability chamber for 24h at 40°C/75%RH. The enteric coated tablets were exposed to 40°C for variable curing durations, 30 min, 1h, and 2h, using a perforated tablet coating pan to evaluate the impact on esomeprazole release. The enteric coated tablets with different curing conditions were subjected to stability conditions at 40°C/75%RH. The dissolution of the tablets was performed using USP apparatus 2 (paddle) at 100 rpm in 0.1N hydrochloric acid for 120 min, followed by a pH 6.8 phosphate buffer for 60 min.

Results: It was observed that 18% w/w of triacetin with respect to Hypromellose Acetate Succinate was optimum for the aqueous dispersion coating using Hypromellose Acetate Succinate.  In the trial with 10% w/w triacetin, the material was spray-dried during the coating process. In contrast, with 25% w/w triacetin, the spray nozzle was blocked. Fig. No. 01 represents the impact of curing temperature on drug release from esomeprazole tablets enteric coated with aqueous dispersion of Hypromellose Acetate Succinate. Fig. No. 02 represents the impact of curing duration on drug release from esomeprazole tablets enteric coated with aqueous dispersion of Hypromellose Acetate Succinate at initial and stability conditions. Fig. No. 03 represents the impact of curing duration on drug release from esomeprazole tablets enteric coated with solvent based dispersion of Hypromellose Phthalate at initial and stability conditions.

Conclusion: In this study, it was observed that there was no significant impact of curing temperature and curing duration on esomeprazole release from tablets enteric coated with either solvent based Hypromellose Phthalate or aqueous dispersion of Hypromellose Acetate Succinate. The post drying of tablets in a perforated coating pan at 40°C for 30 min is sufficient to get stable drug release under stability conditions. In all the performed studies, there was no impact on acid resistance. The scanning electron microscopic study results of enteric coated tablets, either with aqueous dispersion of Hypromellose Acetate Succinate or solvent based Hypromellose Phthalate, also confirmed film integrity at initial and on stability conditions.

Fig. No. 01 Impact of curing temperature on drug release from esomeprazole tablets enteric coated with aqueous dispersion of Hypromellose Acetate Succinate

Fig. No. 02 Impact of curing duration on drug release from esomeprazole tablets enteric coated with aqueous dispersion of Hypromellose Acetate Succinate at initial and stability conditions (40°C/75%RH).

Fig. No. 03 Impact of curing duration on drug release from esomeprazole tablets enteric coated with solvent based dispersion of Hypromellose Phthalate at initial and stability conditions (40°C/75%RH).