Hot melt extruded transdermal films based on amorphous solid dispersions in Eudragit RS PO: The inclusion of hydrophilic additives to develop moisture-activated release systems

• Published in: International journal of pharmaceutics 2016-11, Vol.514 (1), p.270-281
• Main Authors: Albarahmieh, Esra’a, Qi, Sheng, Craig, Duncan Q.M.
• Format: Article
• Language: English
• Subjects: Acrylic Resins - chemistry; Administration, Cutaneous; Amorphous; Chemistry, Pharmaceutical - methods; Crystallization; Drug Liberation; Excipients; Excipients - chemistry; hot melt extrusion; Hydration; Hydrophobic and Hydrophilic Interactions; Methylcellulose - chemistry; Microscopy, Electron, Scanning - methods; Permeability; Pharmaceutical Preparations - chemistry; Physicochemical characterization; Poloxamer - chemistry; Polyethylene Glycols - chemistry; Polymeric drug delivery systems; Polysaccharides, Bacterial - chemistry; Powders - chemistry; Solid dispersions; Solubility; Sucrose - chemistry; Technology, Pharmaceutical - methods; Transdermal; Water - chemistry
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2016.06.137

[Display omitted] A series of Eudragit RS PO-based hot melt extruded films were evaluated as potential transdermal systems, with particular emphasis on the inclusion of hydrophilic excipients to allow water sorption, which in turn would allow drug release on application to the skin. More specifically, sucrose, methyl cellulose, xanthan gum (Xantural®75), poloxamer (Pluronic®F127), Gelucire 44/14 were added to Eudragit RS PO and assessed in terms of physical structure (modulated temperature DSC (MTDSC), thermogravimetric analysis (TGA), powder XRD (PXRD), scanning electron microscopy(SEM)) and in vitro drug release and permeation properties. In addition, the effect of prior hydration on drug permeation was studied for selected systems. Phase separation was noted for sucrose, methylcellulose (high loading), xanthan gum (high loading), poloxamer and Gelucire 44/14 (high loading) using both visual observation and MTDSC. PXRD studies indicated drug crystallization within the phase separated systems. SEM studies broadly followed the same pattern. Dissolution studies indicated that the hydrophilic excipients considerably enhanced the release rate, while Franz diffusion cell studies showed a much greater variability in effectiveness, which we ascribe to the paucity of water of hydration present which would not allow swellable additives such as xanthan to release the drug. However, films containing Gelucire 44/14 emerged as the most satisfactory systems, despite the higher additive loaded systems showing drug phase separation. This may be related to emulsification rather than swelling on contact with water, as noted for the permeation studies involving pre-hydration. This strategy therefore presents a promising approach for triggered transdermal drug delivery, activated by hydration from the skin itself.