Impact of mixing on content uniformity of thin polymer films containing drug micro-doses

Guluzar G. Buyukgoz, Jeremiah N. Castro, Andrew E. Atalla, John G. Pentangelo, Siddharth Tripathi, Rajesh N. Davé

Research output: Contribution to journalArticlepeer-review

Abstract

The impact of mixer type and critical process parameters (CPPs) on critical quality attributes (CQAs), including the drug content uniformity (CU) of slurry-cast polymer films loaded with micro-sized poorly water-soluble drugs were investigated. Previously untested hypothesis was that the best mixer at suitable CPPs promotes uniform drug dispersion within film precursors leading to acceptable dried-film CU at low, ~0.6 wt% drug concentrations. Taguchi design was utilized to select the best of three mixers; low-shear impeller, high-shear planetary, and high-intensity vibrational, for dried-film drug concentration of ~23 wt%. As-received fenofibrate, a model poorly water-soluble drug (~6 µm) was directly mixed with the hydroxypropyl methylcellulose (HPMC) and glycerin aqueous solution. Impeller and planetary mixers yielded desirable film relative standard deviation (RSD), while vibrational mixer could not. For the lowest dried-film drug concentration of ~0.6 wt%, only planetary mixer yielded RSD <6%. The precursor drug homogeneity was a sufficient but not a necessary condition for achieving dried-film RSD <6%. Thus, proper selection of mixer and its CPPs assured desirable film CQAs. However, minor drug particle aggregation was identified via re-dispersion testing which also led to incomplete drug release.

Original languageEnglish (US)
Article number812
JournalPharmaceutics
Volume13
Issue number6
DOIs
StatePublished - Jun 2021

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

Keywords

  • Content uniformity
  • Critical process parameters (CPPs)
  • Homogeneity
  • Low drug concentration
  • Mixing effectiveness
  • Polymer thin films
  • Taguchi design

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