Biophysical elucidation of the mechanism of enhanced drug release and topical delivery from polymeric film-forming systems

Hazel Garvie-Cook, Kit Frederiksen, Karsten Petersson, Richard Guy, Sergey Gordeev

Research output: Contribution to journalArticle

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Abstract

The effect of incorporating the lipidic medium-chain triglyceride (MCT) into polymeric film-forming systems (FFS) for topical drug delivery has been evaluated. First, the in vitro release of betamethasone-17-valerate (BMV), a representative dermatological drug, was determined from FFS comprising either hydrophobic polyacrylate co-polymers, or hydrophilic hydroxypropyl cellulose, with and without MCT. Release was enhanced from both polymers in the presence of MCT. Atomic force microscopy imaging and nanoindentation of FFS with MCT revealed two-phase structured films with softer inclusions (0.5 to 4 μm in diameter) surrounded by a more rigid structure. Chemical mapping with Raman micro-spectroscopy showed that MCT was primarily confined to the inclusions within the polymer, which predominated in the surrounding film. BMV was distributed throughout the film but was more concentrated outside the inclusions. Furthermore, while BMV dissolved better into the hydrophobic films, it was more soluble in the MCT inclusions in hydrophilic films, suggesting its increased availability for diffusion from these softer regions of the polymer and explaining the release enhancement observed. Second, ex vivo skin penetration studies clearly revealed that uptake of BMV was higher from hydrophobic FFS than that from the more hydrophilic polymer due, at least in part, to the superior anti-nucleation efficiency of the former. Drug was quickly taken up into the SC from which it then diffused continuously over a sustained period into the lower, viable skin layers. In the presence of MCT, the overall uptake of BMV was increased and provides the basis for further optimisation of FFS as simple, convenient and sustained formulations for topical therapy.
Original languageEnglish
Pages (from-to)103-112
Number of pages10
JournalJournal of Controlled Release
Volume212
Early online date16 Jun 2015
DOIs
Publication statusPublished - 28 Aug 2015

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Betamethasone Valerate
Triglycerides
Polymers
Skin
Raman Spectrum Analysis
Atomic Force Microscopy
Drug Delivery Systems
Drug Liberation
Pharmaceutical Preparations

Keywords

  • Polymeric film-forming systems
  • Topical drug delivery
  • Atomic force microscopy
  • Raman chemical mapping
  • Supersaturation
  • Anti-nucleation

Cite this

Biophysical elucidation of the mechanism of enhanced drug release and topical delivery from polymeric film-forming systems. / Garvie-Cook, Hazel; Frederiksen, Kit; Petersson, Karsten; Guy, Richard; Gordeev, Sergey.

In: Journal of Controlled Release, Vol. 212, 28.08.2015, p. 103-112.

Research output: Contribution to journalArticle

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