Zero-order release of poorly water-soluble drug from polymeric films made via aqueous slurry casting

Lu Zhang, Joy Alfano, Doran Race, Rajesh N. Davé

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)245-254
Number of pages10
JournalEuropean Journal of Pharmaceutical Sciences
Volume117
DOIs
StatePublished - May 30 2018

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

Keywords

  • Hydrophilic film matrix
  • Multiple-layer films
  • Poorly water-soluble drug
  • Sustained release
  • Thick films
  • Zero order release

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