Coated hard capsules as the pH-dependent drug transport systems to ileo-colonic compartment

Abstract

Purpose: The aim of this study was to investigate the suitability of hard capsules of different composition (gelatin—G, gelatin coated with hydroxypropyl cellulose—G/HPC, and hypromellose—H) for a coating with aqueous dispersion of pH-dependent synthetic polymer Eudragit^® FS (E_FS) and to evaluate in vitro the coated capsules as transport systems for ileo-colonic drug delivery.

Methods: Three sets of hard capsules with increasing coating levels (5–30%) were obtained by Wurster technique. The release of model drug (caffeine) from prepared samples was tested using paddle dissolution method with continual pH change (pH 1.2–2 h, 6.8–4 h and 7.5–2 h).

Results: During the coating process, no problems occurred and similar suitability of capsules materials for E_FS application was observed in contrast to some published reports. The application of HPC subcoating onto gelatin capsules surface was shown as the redundant step. The samples G/E_FS10–15% and H/E_FS15–20% with 6 h lag time and fast drug release after the pH adjustment to 7.5 corresponded with the requirements for ileic drug delivery. Samples releasing the drug after the pH change to 7.5 in 2-h interval such as G/E_FS 20%, G/HPC/E_FS 25% and H/E_FS 25% are considered as promising transport systems to ileo-colonic area. Samples G/E_FS 25–30%, G/HPC/E_FS 30% and H/E_FS 30% with 7 h lag time could be used for colon delivery.

Conclusion: The desired intestinal part could be targeted without significant formulation changes only by the selection of capsules shell forming material and suitable E_FS coating thickness.

Keywords::

• Gelatin hard capsules
• hypromelose hard capsules
• Eudragit® FS
• ileum delivery
• colon delivery
• dissolution test

Acknowledgments

We are grateful to pharmaceutical companies CAPSUGEL providing the gelatin and HPMC capsules, EVONIC RÖHM supplying coating material Eudragit^® FS 30 D and by Czech pharmaceutical company ZENTIVA, a.s. as the donator of active ingredience and excipients.

Declaration of interest

This experimental work was realized by support IGA VFU Brno Czech Republic, project 136/2008/FaF and IGA Ministry of Health, Czech Republic, project NS10222-2/2009.