PheroidTM-based anti-malarial formulations : HPLC method development and stability studies

Abstract

Malaria remains one on the world's most common infectious diseases with 300 to 500 million cases every year. The current treatment of malaria is restricted due to ever increasing drug resistance, cost of treatment and the availability of treatment. When looking at solutions for these problems, new drug delivery systems should be taken into consideration. The Pheroid™ drug delivery system which incorporates Pheroid™ technology can be placed in this category and the stability of anti-malarial drugs in combination with the Pheroid™ drug delivery system was investigated. The main objectives of this study were the development of HPLC methods for the analysis of the anti-malarials in the Pheroid™ drug delivery system, the validation of the HPLC methods developed and the determination of drug stability of the formulated products during accelerated stability conditions. Mefioquine HCI and chloroquine phosphate were each separately formulated in both the Pheroid™ and pro-Pheroid systems. HPLC analysis was done after each month according to the different assay methods. Accelerated stability studies, conducted on the four products formulated, indicate that only chloroquine phosphate in Pheroid™ complies with speCifications. This product may be further developed for possible commercialisation. It was found that chloroquine phosphate cannot be fomlulated with pro-Pheroid, because of solubility issues. Results for mefioquine HCI in microsponges were inconclusive. Assay values for months 1 and 3 were low, whilst values for month 2 were much higher. Despite the fact that mefloquine HCI in pro-Pheroid did not comply with assay specifications, the results obtained were consistent. With the HPLC assay methods used, peak interference from the Pheroid™ system was significant. It would be advisable to further develop the methods to eliminate this problem. Questionable results may then be re-examined to distinguish between poor product performance and analytical issues.