| Popis: |
In recent years, there has been a growing interest towards the use of transdermal drug delivery systems (TDDS). However, a great challenge in this arena is the formidable barrier posed by the skin that can limit permeation of therapeutic agents. Therefore, there is a need for novel strategies or enhancement techniques to deliver the drug across the skin. The use of hot melt extrusion technology (HME) to prepare these TDDS is also generating considerable interest in the pharmaceutical field. This work combines these interests through preparation of several hot melt extruded formulations screened for their potential for transdermal development. A substantial database has been generated on physicochemical characteristics of these formulations with a prime focus on their in vitro drug release and permeation properties. Processing parameters (temperature, heating duration and mixing speed) for preparing hot melt extruded compositions comprising ibuprofen (model drug) and various carrier excipients were established with minimal thermal degradation. Ibuprofen displayed a plasticizing effect enough to perform extrusion. HME processing facilitated the formation of solid solutions and dispersions. The feasibility of delivering ibuprofen from Eudragit RS PO-based extruded patches was investigated. The formation of solid solutions with high drug loading (35% w/w) was achieved in relatively stable extruded Eudragit RS PO matrices under dry conditions. However, these systems were associated with limited drug release. This has given the way to explore the effect of addition of release modifiers (sucrose, methylcellulose, Xantural®75, Pluronic® F127, Gelucire 44/14) and hydration influence. Gelucire 44/14 containing formulations emerged as the most satisfactory systems which improved in vitro drug permeation profiles significantly by means of hydration. Intriguing structural changes upon hydration are believed to facilitate drug release as observed from the medicated and non-medicated formulations. These include consistency changes, softening of the extruded films and surface imperfections. Similar changes were detected in vivo using non-medicated Eudragit RS PO/Gelucire 44/14 carrier extruded systems after human skin occlusion. This employed strategy holds the promise for potential of a novel transdermal drug delivery activated by hydration. |
