Preparation, Characterization And In Vitro Release Behaviors Of Hydrophobic Drug/hydrophilic Drug-loaded PCL Implants

Praziquantel (PZQ) is a hydropHobic drug (water solubility about 400ug/ml ) widely used in developing countries for the treatment of schistosomiasis and hydatid. To date, the common dosage form of PZQ is tablet, and its frequent administration is needed in order to decrease morbidity. It is necessary to develop a long-term controlled release PZQ implant. 5-fluorouracil represents a rationally designed class of anticancer agents. Remarkable progress has been made over the forty years in elucidating the cellular and clinical pHarmacology of 5-Fu, its mechanisms of action, and the determinants of sensitivity. 5-Fu is a hydropHilic drug whose solubility in water is about 17mg/ml. However,administration of the compound often causes severe gastrointestinal toxicity and myelosuppression, and 5-Fu's very short plasma half-life(approximately 11 minutes ) makes this drug particularly suitable to be delivered as drug sustained release implant. Poly(ε-caprolactone) (PCL) is one of the most potential candidates for the purpose due to its availability, biodegradability, non-toxicity and biocompatibility to many drugs. In this study, Praziquantel (PZQ)-loaded poly(ε-caprolactone) (PCL) cylindrical implants and 5-fluorouracil(5-Fu) -loaded poly(ε-caprolactone) (PCL) cylindrical implants were fabricated using poly(ε-caprolactone) (PCL) as carrier. The cylindrical implants with a diameter of 3, 4 or 8mm were prepared by fully blending PZQ /5-Fuparticles with melting PCL at different ratios (25:75 and 50:50, w/w) and then molding the blends with a lab-scale injection moulder with a diameter of 3, 4 or 8mm. The resultant blend was collected and further molded into implants using a lab-scale injection moulder at 70 ?C. The cylindrical implants were end-capped by pressing a PCL sheet on the end surface of the implant.Implant diameter (3, 4 and 8 mm), drug loading (25% and 50%), and the end-capping were investigated to evaluate their effects on drug release. The evolution of implants with release time was conducted in terms of implant structure, crystallinity, drug content and molecular weight of PCL. The results showed that drug release was fastest for the implant with a diameter of 3mm and slowest for the implant with a diameter of 8mm; drug release from the implant with a drug content of 50% was faster than that from the implant with a drug content of 25%; the release of PZQ from the end-capped implants was slightly slower than that from the corresponding end-uncapped implants. The effect of drug loadings on PZQ release was related with diameter of the implants and the effect was weakened as diameter of the implants increased. The drug release data for all the implants were best fitted with Ritger–Peppas model, therefore Fickian diffusion was the predominant release mechanism. The evolution of implants with release time verified that PZQ was gradually released from the exterior to the interior of the implants. The results of 5-Fu-loaded PCL implants are same with PZQ-loaded PCL implants.