Background: The need for parenteral administration of arteether (ART) as intramuscular (IM) injection for three consecutive days often proves a major constraint for patient compliance. The present study reports development of an in situ IM implant to provide sustained release of ART over 72h.
Objective: The development of self microemulsifying drug delivery system (SMEDDS) based lyotropic liquid crystalline preconcentrates (LLCPr) comprising oil, surfactant and cosurfactants with a biodegradable polymer (P-LLCPr) which undergo rapid transition to liquid crystalline phase (LCP) to form an in situ gel following IM injection.
Methods: The P-LLCPr was prepared by mixing oil and surfactant. PLGA was dissolved in cosurfactant, added to this blend and vortex was mixed. The LLCPr (without polymer) and P-LLCPr were evaluated for conversion into LCP by polarization optical microscopy (POM), XRD, gel strength, particle size, zeta potential and sustained release by ex vivo method in muscle of G. domesticus.
Results: POM and XRD study confirmed the formation of anisotropic LCP. A force of <25N revealed good injectability of the LLCPr and P-LLCPr in vitro, and ex vivo in the extensor digitorum longus (EDL) muscle of G. domesticus. Implant formation was observed both in vitro and ex vivo. The P-LLCPr formed a stiff gel which exhibited a 4 fold enhancement in gel strength compared to LLCPr. The particle size of P-LLCPr was 120 ± 1.5nm and zeta potential -14.56 mV. The ex vivo release method in EDL muscle, developed to mimic in vivo conditions revealed 100% release in <24 h from ART solution and LLCPr. The P-LLCPr however exhibited sustained release of ART for >48h.
Conclusion: The sustained release P-LLCPr of ART suggests great promise as a single shot therapy for the treatment of malaria with enhanced patient compliance.