Supervisors info:
Παρασκευάς Δάλλας, Επίκουρος Καθηγητής, Τμήμα Φαρμακευτικής, ΕΚΠΑ
Δημήτριος Ρέκκας, Αναπληρωτής Καθηγητής, Τμήμα Φαρμακευτικής, ΕΚΠΑ
Μιχαήλ Ράλλης, Επίκουρος Καθηγητής, Τμήμα Φαρμακευτικής, ΕΚΠΑ
Summary:
Transdermal administration of active pharmaceutical ingredients (APIs), if achievable, presents considerable advantages compared to conventional routes of administration, i.e. oral and intravenous routes, such as avoiding the first-pass metabolism, provide sustained and constant plasma levels and improving patient compliance.
Aim of the present study was to assess the in vitro permeation of APIs with weakly basic character, active substance A and active substance B, through human cadaver epidermis as a preliminary step towards the development of transdermal therapeutic systems (TTSs) with desired release rate. In this context, the effect of some factors, specifically chemical form of APIs, composition of transdermal delivery vehicle and skin from different donors, has been studied.
The in vitro transdermal permeation experiments were conducted using modified, vertical Franz type diffusion cells and human epidermis of different donors, female sex.
Gels containing active substance A in the form of hydrochloric acid (A-HCl) showed extremely low Q values, the amount of A-HCl penetrating the epidermis per unit area in units of ug/cm2, at 12, 24, 36 and 48 h since the beginning of the experiment. Neither the different organic solvent of the delivery vehicle nor the skin from different donor affected statistically significant its absorption, with the consequence that the flow is in any case insufficient.
Gels containing active substance in the form of weak base showed higher Q values at all sampling times, achieving therapeutic levels for more than 48 h following administration of a reservoir-type TTS of less than 12 cm2. Concerning Drug-in-Adhesive (DIA) type TTSs, monolithic patches were not functional due to the volatility of the API at temperature above 35ºC and that was the reason why multilaminate – sandwich patches were tested. However, although the original problem was encountered, there was large deviation in the concentration of active substance A from the theoretical value, possibly due to either the backing membrane or the pressure sensitive adhesive (PSA).
Finally, regarding gels containing active substance B in the form of weak base, they did not show sufficient Q values to achieve therapeutic plasma levels from TTSs of acceptable area. In addition, the increasing ethanol content and the corresponding change in API concentration did not show similar effect on the flow rate through the skin.
It is concluded, therefore, that plasma levels of APIs following transdermal administration of weak bases are significantly higher compared to the administration of corresponding salts. Furthermore, the administration of active substance A is feasible from reservoir-type TTSs whereas active substance B requires further study to assess its percutaneous permeation.
Keywords:
Transdermal administration, weak base, stratum corneum, in vitro permeability, transdermal therapeutic systems, reservoir patch, Drug-in-Adhesive patch
