Effect Of Process Parameters On Co-precipitation Of Paclitaxel And Poly(l-lactic Acid) By Supercritical Antisolvent Process

Paclitaxel (PTX) is one of the most effective anti-cancer drugs. However, PTX is almost insoluble in water (<0.004mg/ml) and common solvents. The current clinical formulation of PTX contains 1:1 blend of Cremophor EL (polyethoxylated castor oil) and dehydrated ethanol. This formulation leads to low bioavailability, toxicity and hypersensitivity. For reduce side effects and increase therapeutic efficiency, much effort has been devoted to developing a new drug delivery system (DDS) without Cremophor EL for PTX. Supercritical anti-solvent (SAS) is an attractive technique for preparing DDS, which can effectively control the particle size and distribution of DDS by changing operating parameters. Also SAS is low residual solvent and environment friendly technique. In this paper, DDS of PTX were prepared by SAS process, and the effects of SAS process parameters on DDS particles were investigated.The mixed solvents of Dichloromethane (DCM) /ethanol (EtOH) and DCM/Dimethyl sulfoxide (DMSO) were used to dissolve PTX and PLLA, and PTX loaded PLLA submicro-particles were prepared by SAS process. The effect of process parameters on DDS, including temperature (30-45oC), pressure (80-140bar), polymer concentration (5-12g/L) and solution flow rate (0.2-1.5ml/min), were investigated. SEM, laser particle size analyser and HPLC were employed to investigate the effect of process parameters on particles morphology, size and drug loading efficiency.The results indicate that the solvents ratios have a great effect on the particles morphologies. Good morphology particles were collected when DCM/EtOH was used. Particles drug loading efficiency is changed according to DMSO volume ratio in DCM. It is further demonstrated that the particles size and drug loading efficiency increase with increased pressure. The average size of particles increase when increase the flow rate of the solution. And particles have drug loading efficiency of 86.8% when the concentration ratio of PLLA/PTX is 5:1.This work will be useful for preparing DDS particles by SAS process.