Dissolution improvement of poorly water-soluble drug by cogrinding method using jar mill

As a representative proton pump inhibitor, Lansoprazole was poorly soluble in water which caused the low oral bioavailability. The present study was carried out to enhance the dissolution of lansoprazole by cogrinding with some commonly used hydrophilic polymers (β-CD, PVP, HPMC, L-HPC, CS, PEG and PVPP) in the weight ratio of 1:1 for 2 h in the jar mill. Samples of coground mixture, micronised drug, and physical mixture were characterized by XRPD, and DSC, the results showed that the drug crystallinity reduced in the coground process. The amount of drug released from the coground mixtures in PBS (pH 6.8，37oC) in 30 min was 100% approximately (except the coground mixtures prepared with VPP or PEG) while released from the micronised drug was just about 20%. Increasing the hydrophilicity and diminishing the size of drug particles by cogrinding were the main causes for enhancing the dissolution of the drug. The results of the stability study of lansoprazole in coground mixture showed that there were no significant changes in the drug content and dissolution characteristics 6 months later. It is clear that the cogrinding method described in the article is very effective for enhancing the dissolution of the poorly soluble drugs, and it is easy for industrialization, showing a strong potential for future applications.