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

Abstract

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 prehydration. This strategy therefore presents a promising approach for triggered transdermal drug delivery, activated by hydration from the skin itself.

Tenofovir Hot-Melt Granulation using Gelucire® to Develop Sustained-Release Vaginal Systems for Weekly Protection against Sexual Transmission of HIV

“…There are hardly any differences between G43 and G39, and both are crystalline (as observed in HSM) with two intense peaks at 20.9 and 23.1° 2θ. This agrees with the results obtained for other Gelucire ® , which also present peaks at between 20–25° 2θ [33]. A third peak of lower intensity can also be distinguished at around 6.8° 2θ, which is more clearly visible in G39 (Figure 5).…”

Insoluble Polymers in Solid Dispersions for Improving Bioavailability of Poorly Water-Soluble Drugs

“…Amorphous SDs with Eudragit ® RS PO are developed for transdermal films because a high concentration of the released drug may enhance skin permeability [101]. However, hydrophilic excipients (e.g., gelucire, xanthan gum) are suggested to be incorporated into transdermal systems to allow water sorption and create triggered drug delivery systems [101].…”

An update on the contribution of hot-melt extrusion technology to novel drug delivery in the twenty-first century: part I

“…In general, the advantages of HME technology are the absence of solvents, which prevents risk of chemical degradation (in case of aqueous solvents) and residual organic solvents limits [26]; ease of scalability and CM by adapting process analytical tools [27,28]; few processing steps, which makes it cost-and time-effective [29,30]; improved solubility and bioavailability of poorly water-soluble drugs [26,31,32]; modification of drug release to delayed or sustained release [33,34]; and development of various pharmaceutical drug delivery systems [35,36,37,38,39,40]. Figure 2 represents the critical parameters involved in the development of various dosage forms by HME.…”