In vitro controlled release of finasteride from in situ polymer precipitation delivery system
Seah, Xin Ying
Date of Issue2015
School of Materials Science and Engineering
Androgenic alopecia (AGA) is a prevalent disease which is commonly treated with oral finasteride. Nevertheless, the possible side effects and poor patient compliance associated with it made it an undesirable treatment. Injectable In situ polymer precipitation (ISPP) has been an attractive form of administration. It harnesses the benefits of being a non-invasive but localized delivery system. Its ease of manufacturing and tunable properties to incorporate a wide spectrum of different drugs sees promising applications in many treatments. This study aims to understand the effects of the various tuning parameters of an ISPP system on the release profiles of finasteride for the treatment of AGA. This is to investigate the possibility of a sustainable, efficacious alternative treatment for AGA patients. In this study, three major tuning parameters have been explored namely drug loading, addition of co-solvent and the use of long chain polymers. The burst release and release in the diffusion phase was found to plateau with increasing drug loading. Further investigation showed the inadequate sink condition provided by less than 100ml of buffer medium was the limiting factor for intrinsic drug release during burst release. Also during the diffusion phase, the large aggregates formed from drug loading beyond saturation resulted in a drug release that was lower than expected. Addition of co-solvent triacetin was found to suppress burst release amongst low drug loading formulations due to the slower phase inversion rate. Nevertheless, in higher drug loading formulations, the enlarged surface area of high triacetin formulation played a more influential role resulting in an unexpectedly higher burst release. In addition, higher triacetin content formulations seemed to give higher release in the diffusion phase. This was attributed to the earlier onset of polymer degradation phase of co-solvent systems. The use of long chain polymer saw high burst and a low subsequent release deemed long chain PLGA with no modifications an undesirable option in achieving a zero order release profile. A final assessment indicated two promising formulations 0.4g of F460 and 0.2g of F433 which could potentially deliver a continuous therapeutic dose for more than a month. However further experiments are required to verify the safety and efficacy of these formulations in vivo.