Enteric-coated HPMC capsules: Comparison of enteric coatings and investigation of relationship between in-vitro disintegration and dissolution times

Polymeric film coating of oral solid dosage forms may generate products that exhibit controlled release of active ingredients, physical and chemical protection of the ingredients from the external environment as well as taste masking properties. Among controlled release products, sustained and delayed release profiles are prominent. For the former, the drug is released gradually over time whereas for the latter, drug release occurs rapidly following a predefined lag-time. Thus, drugs can be delivered to the small intestine as exemplified by pH-sensitive coatings of solid dosage forms.

HPMC (hydroxypropyl methylcellulose) capsules have been available commercially, mainly to the dietary supplement industry as a vegetarian alternative to gelatin, for more than 10 years. Enteric-coated filled HPMC hard capsules are also frequently applied as clinical trial formulations in early stages of clinical investigations since some new chemical entities (NCE’s) are prone to instability in gastric fluids or irritate the gastric mucosa. Furthermore, the limited amount of drug substance available at early development stages often precludes the development of other solid dosage forms, such as coated pellets or tablets. Advantages result from the ability to coat a capsule, since the coating process is independent of the capsule contents thus avoiding extensive formulation development.

During capsule coating challenges are generally due to the characteristics of the capsule wall. In particular, for gelatin-based capsules, the shell may soften and become sticky upon spraying of aqueous enteric polymer dispersions or it may become brittle due to water evaporation during drying with consecutive loss of mechanical stability. Furthermore, insufficient adhesion of the film with splintering and peeling of the coat (orange peel effect), especially with organic spray formulations has been reported. In this respect, HPMC capsules offer the advantage of less sensitivity to aqueous coatings if appropriate sealing, i.e. closure of the gap between the capsule body and the cap is obtained to avoid leaking of the capsule content into the stomach or vice versa. Moreover, site-specific delivery of HPMC capsules was claimed by using coating materials with different pH-dependent solubilities, i.e. dissolving at pH ≥5.5 and pH ≥7 for upper GI and colonic delivery, respectively. A comparison between gelatin versus HPMC capsules coated with acrylic polymers Eudragit L and S 12.5 demonstrated that the gelatin capsules resulted in brittle film coats with insufficient adhesion on the smooth capsule surface [6]. Since the surface of HPMC is more ragged compared with gelatin capsules. HPMC materials may lend themselves to better polymer coat adhesion. Download the thesis here: enteric-coated-hpmc-capsules.pdf

Dissertation zur Erlangung des Grades “Doktor der Naturwissenschaften” am Fachbereich Chemie, Pharmazie und Geowissenschaften der Johannes Gutenberg-Universität Mainz

Maoqi Fu, geb. in Ürümqi , China

Mainz, 2020