Preparation Of Drug Microparticles And Drug-Carrier Coprecipitates By Gas Antisolvent Technology

This work is to prepare the ultrafme particles of Nimodipine (NMD) by GAS (Gas Antisolvent) technique and to prepare the Nimodipine (NMD)-Polyethylene Glycol(PEG6000) particles by GAS copercipition technique.The solubility of NMD in supercritical CO2 was first measured within a large range of pressure and temperature. The effects of temperature and pressure on the solubility were investigated. It was found that NMD has poor solubility in SC-CO2 and its solubility increases with the increasing of pressure and temperature in certain range. The retrograde area as reported in some literatures was found when pressure was low enough.In GAS process, NMD particles prepared are generally smaller, more uniform and better morphology than the starting material. Size of particles was found to decrease with the increasing of the solution concentration and the rising rate of pressure. Temperature and pressure of precipitator have no obvious effect on the size of the particles.NMD-PEG6000 copercipitates could be prepared by GAS process. The change in particles size and morphology of the drug crystals were studied. The copercipatates with different shapes could be obtained under different experiment conditions. When ethanol was selected as solvent, higher PEG-NMD ratio led to more anomalistic particle shape and bigger particle size, and increasing temperature could bring smaller products. However, when acetone was used as solvent, temperature and drug-carrier ratio had little effect on the products. Furthermore, the size of particles decreases obviously when the rising rate of pressure increases with acetone or ethanol.The dissolution rate of NMD ultrafme particles and NMD-PEG6000 copercipitates prepared were measured. The microparticle products had a better dissolution rate compared to the starting material, and the supporting of drug on a hydrophilic carrier of PEG 6000 enhanced release dosage form farther. NMD-PEG6000 coprecipitates show a remarkable enhancement in drug dissolution rate. It was found that the increasing the amount of carrier can enhance the drug dissolution rate.