Tesis doctoral de Ana Melero Zaera
The thesis project is the development of a transdermal patch containing nortriptyline hydrochloride (nth), an antidepressant drug which has been shown to be effective in the support therapy for smoking cessation [1-8]. this drug has some problems, mainly due to its low bioavailability and its high variability. Besides, it presents side effects, such as dry mouth, drowsiness, orthostatic hypotension, urinary retention, sexual problems, constipation, and rapid or irregular heartbeat. Many of these drawbacks are partially associated to first pass metabolism (liver and intestinal) and fluctuation of plasma peak levels due to oral administration. By the use of an alternative way of administration, which avoids the pass of the drug through the intestine and liver, these difficulties can be overcome. The transdermal route meets this requirements and presents other advantages as being very comfortable and easy to use for the patients [9, 10]. These considerations make it an attractive and innovative way of administration of drugs that has been included in the advanced drug delivery systems list. in order to design a novel tds of nth, we studied initially the behaviour of the drug through human heat separated epidermis (hhse). The assays were carried out in the absence and presence of chemical enhancers, which were representative of the most common groups of them, under two different ph conditions, using franz diffusion cells (fdc). The next step was to elaborate different formulation alternatives containing the drug of interest and the most effective enhancers. Hydroxy-propyl-methyl-cellulose (hpmc) has been used as the film forming polymer. A group of seven formulations were chosen according to its appearance. They have been characterized on the basis of thickness, uniformity of drug distribution in the matrix, release profile and diffusion through human heat separated epidermis. The penetration profile of nth has been investigated using the so called saarbrí¼cken-model, which combines a tape-stripping removal of the stratum corneum and cryosection of the deeper skin layers, after an incubation time of 3 h, 6 h and 24 h. Finally, the diffusion of nth through wistar rat full thickness skin (wfts) was studied and a correlation between the parameters obtained for both skin types was estimated in order to establish a basis for possible future in vivo investigations to test this formulations. the future work will be devoted to in vivo studies on wistar rat.
Datos académicos de la tesis doctoral «Development of anortriptyline hydrochloride transdermal patch as support therapy for smoking cessation«
- Título de la tesis: Development of anortriptyline hydrochloride transdermal patch as support therapy for smoking cessation
- Autor: Ana Melero Zaera
- Universidad: Universitat de valéncia (estudi general)
- Fecha de lectura de la tesis: 29/05/2009
Dirección y tribunal
- Director de la tesis
- Teresa María Garrigues Pelufo
- Tribunal
- Presidente del tribunal: ulrich f Schaefer
- ben Forbes (vocal)
- amalia Rodríguez bayón (vocal)
- José ricardo Nalda molina (vocal)