Drug release from HPMC matrices in milk and fat-rich emulsions

Hywel David Williams, Kevin P Nott, Dave Barrett, Robert Ward, Ian J Hardy, Colin D Melia

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40 Citations (Scopus)


Biorelevant media for the fed stomach, including fat emulsions, are routinely used during in vitro testing of solid dosage forms. However, their complexity undoubtedly creates difficulties in identifying factors which affect drug release. Here, we show fats can directly influence drug release from hydroxypropyl methylcellulose (HPMC; Methocel K4M) matrices which are often subjected to biorelevant testing. Model fat systems included milk (0.1 -3.5 fat) and the parenteral emulsion Intralipid (R) (20 -30 fat). The matrix showed good extended-release properties for at least 12 h in these media (USP-1/USP-4), but at the highest fat concentration, release was retarded and shifted towards zero-order release. Confocal imaging studies using a water-soluble (fluorescein) and fat-soluble (Nile red) fluorophore provided evidence of phase separation of Intralipid (R) at the surface of the emerging gel. Combined magnetic resonance imaging-USP-4 drug release testing provided further evidence for deposition of fat on the tablets. We propose that the aqueous portion of the emulsion is removed by the hydrating matrix, causing coalescence and deposition of a fat layer at the surface, and these deposits cause slower drug release by reducing the matrix surface area available for release. Therefore, there is a risk of a direct interaction between fat emulsions and HPMC tablets, with resultant effects on drug release in vitro. (C) 2011 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100: 4823-4835, 2011
Original languageEnglish
Pages (from-to)4823 - 4835
Number of pages13
JournalJournal of Pharmaceutical Sciences
Issue number11
Publication statusPublished - 2011
Externally publishedYes

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