Enteric-coated HPMC capsules: Comparison of enteric coatings and investigation of relationship between in-vitro disintegration and dissolution times
Date issued
Authors
Fu, Maoqi
Editors
Journal Title
Journal ISSN
Volume Title
Publisher
License
Abstract
An investigation was performed on the utility of various enteric polymers for use in coating hard shell capsules. This type of preparations is of particular importance during early clinical trials, as it reduces the burden associated with formulation development for API’s in need of enteric coating. A wide range of different polymers was investigated, and it was found that those polymers lead to differences in the performance parameters.
HP-55S was found (even without adding plasticizers) to provide by far the best coating in terms of closing the gap between capsule cap and body as well as providing a smooth surface as shown by scanning electron microscopy images. This was reflected by the clearly superior performance of this polymer in terms of the acid resistance of coated capsules in both 0.1 and 0.01 M HCl. Addition of talc was generally beneficial in terms of coat quality because of its bulking up effect on the coat, which helps in closing the gap.
Delayed release capsule shells showed poor performance in terms of resisting acid uptake into the capsule even though they could prevent the contents from being released in the medium. This indicates that while possibly useful for preventing gastric release of irritating substances, they are not dependable for the protection of acid-labile compounds against gastric juice, and therefore incapable of obviating the need for capsule coating.
In terms of disintegration performance, HP-50 was found to provide the fastest disintegration. This might be related to the low interfacial pH the polymer needs to dissolve. TEC had limited effect on disintegration except for HPMCAS-MG were higher TEC content led to longer disintegration times, most probably owing to increased film flexibility and continuity.
A further significant observation was the biorelevant medium of Al-Gousous et al consistently giving longer disintegration times compared to the compendial and blank FaSSIF media. This, in addition to instance of TEC level effect being detected by this medium but not by the compendial one, shows that proper selection of test media is important particularly when dealing with API’s that have a preferential absorption site in the proximal small intestine.
Whether disintegration results can be considered reflective of API release was also investigated. It was found that disintegration performance correlated well to early, middle and late stages of the dissolution process both in paddle and basket devices. This indicates that using disintegration testing as a quick screening tool during enteric formulation development is justified.