Estudios galénicos de nuevas terapias analgésicas tópicas

Resumen

PhD Thesis - Summary: GALENIC STUDIES OF NEW TOPICAL ANALGESIC THERAPIES (ESTUDIOS GALÉNICOS DE NUEVAS TERAPIAS ANALGÉSICAS TÓPICAS) There is not currently available a therapy of choice for analgesic treatment in some painful conditions as oral mucositis in oncologic patients receiving chemotherapy and/or radiotherapy nor in women suffering from painful healing process in the vagina. On this regard, and based on the known analgesic effect of a doxepin rinse in oral mucositis, there are proposed new analgesic therapies. Research is focused on the galenic studies to develop two new semisolid formulations for pain treatment in mucosa (for buccal and vaginal use, respectively). Development studies include selection of the most suitable permeation enhancers to overcome the known low intrinsic permeation of doxepin. Franz cell diffusion systems are employed using either an artificial membrane (in vitro studies) or porcine buccal mucosa (ex vivo studies) to select the most promising candidate for optimal doxepin release and doxepin permeation and retention in mucosa. Final oral formulation consists of doxepin (5%), methol (5%), Transcutol® (10%) and Orabase® (q.s.). Chosen formulation is also tested at in vivo level in pigs to confirm previous results and study the potential doxepin systemic absorption following its buccal application. Additionally, rheological studies are also performed. Same composition as regards active substance and permeation enhancers is proposed for the vaginal formulation, using the mucoadhesive base Orafix® instead. Besides also studying its release, permeation and retention in vaginal mucosa, the formulation is characterised at physico-chemical and microbiological level, including a stability study. Formulation is also tested for bioadhesive, syringeability and rheological properties. Research includes the ICH validation of the quantitative analytical methods for doxepin determination plus the study of doxepin pharmacokinetics in pigs, as it is not already published in the literature. This thesis lays the foundation for further research at clinical level with the view to potentially adopting these new therapies for analgesia in oral mucositis and painful painful healing process.