Zero-order release of poorly water-soluble drug from polymeric films made via aqueous slurry casting
Document Type
Article
Publication Date
5-30-2018
Abstract
In spite of significant recent interest in polymeric films containing poorly water-soluble drugs, dissolution mechanism of thicker films has not been investigated. Consequently, release mechanisms of poorly water-soluble drugs from thicker hydroxypropyl methylcellulose (HPMC) films are investigated, including assessing thickness above which they exhibit zero-order drug release. Micronized, surface modified particles of griseofulvin, a model drug of BSC class II, were incorporated into aqueous slurry-cast films of different thicknesses (100, 500, 1000, 1500 and 2000 μm). Films 1000 μm and thicker were formed by either stacking two or more layers of ~500 μm, or forming a monolithic thick film. Compared to monolithic thick films, stacked films required simpler manufacturing process (easier casting, short drying time) and resulted in better critical quality attributes (appearance, uniformity of thickness and drug per unit area). Both the film forming approaches exhibited similar release profiles and followed the semi-empirical power law. As thickness increased from 100 μm to 2000 μm, the release mechanism changed from Fickian diffusion to zero-order release for films ≥1000 μm. The diffusional power law exponent, n, achieved value of 1, confirming zero-order release, whereas the percentage drug release varied linearly with sample surface area, and sample thickness due to fixed sample diameter. Thus, multi-layer hydrophilic polymer aqueous slurry-cast thick films containing poorly water-soluble drug particles provide a convenient dosage form capable of zero-order drug release with release time modulated through number of layers.
Identifier
85042784614 (Scopus)
Publication Title
European Journal of Pharmaceutical Sciences
External Full Text Location
https://doi.org/10.1016/j.ejps.2018.02.029
e-ISSN
18790720
ISSN
09280987
PubMed ID
29499350
First Page
245
Last Page
254
Volume
117
Grant
EEC-0540855
Fund Ref
National Science Foundation
Recommended Citation
Zhang, Lu; Alfano, Joy; Race, Doran; and Davé, Rajesh N., "Zero-order release of poorly water-soluble drug from polymeric films made via aqueous slurry casting" (2018). Faculty Publications. 8651.
https://digitalcommons.njit.edu/fac_pubs/8651
