Study On LPM And LPM Nanocrystal

Objective:In this study,LH as a model drug for schizophrenia treatment was designed and studied,combined with nanocrystalline technology,to prepare and screen a new long-acting injection against schizophrenia,to evaluate its release in vitro.To explore the preparation characteristics and efficacy advantages of nanocrystal,and lay a good theoretical and experimental foundation for the development of such new drugs.Method:LPM was synthesized by a series of reactions between pamoic acid and LR.The physical characterization of LPM,LR,LH and the products obtained under different reaction conditions LRP,LHP,etc.The products were determined by comparative analysis of the results of SEM,XRD,DSC,~1HNMR and FTIR.The appearance,melting point,characteristic absorption peak and fingerprint region were taken as the main investigation factor to determine whether LPM crystal is formed.The preparation process of LPM nanocrystals was optimized by design-expert method,and the optimal prescription was verified.The microscopic characteristics of LPM nanocrystals,particle size,morphology and crystal form,were observed by particle size analyzer,transmission electron microscopy,X-ray diffraction and differential scanning calorimeter.A method for the determination of LPM was established.By comparing the solubility and in vitro release characteristics of LPM nanocrystals with LPM raw materials,the nano-effects of LPM nanocrystals in improving drug solubility and release rate were evaluated.Results:The preparation method of LPM was determined.According to the physical characterization results of LR,LH,LHP,LRP,LHPM,LRPM and LPM,it can be seen that LPM is a new kind of palmitate different from the first six compounds.It is crystalline,regular in shape and stable in structure.LPM has low solubility,and the maximum solubility is 73?g/mL at pH 7.8.LPM nanocrystals were prepared by high pressure homogenization method.The single factor experiments investigated the kinds and concentration of surfactants,the concentration of LPM,homogenization pressure and cycle times,and determined that the stabilizer was poloxamer 188 with a concentration of 0.1%.The results of the optimum preparation process by design-response surface methodology were as follows:the concentration of main drug was 0.55 mg/mL,homogenization pressure was 400 bar,and cycle times were 18.The average particle size of three batches of samples prepared in parallel under the optimized conditions was(286.4±0.8)nm and PDI was0.252±0.005.The experimental results showed that the preparation process was stable and the sample reproducibility was good.The preparation process of LPM nanocrystals was determined.The method is stable and accurate.A method for in vitro release of LPM was established.After the preparation of LPM nanocrystals,the solubility of LPM nanocrystals was improved and the release rate was stable.There was no sudden release.Conclution:The preparation and in vitro release of LPM long-acting injection were studied.The results showed that LPM was a new dihydroxynaphthalate with low solubility,and it was feasible to prepare growth-effective nanocrystal.The cumulative release rate of LPM nanocrystalline suspension is much higher than that of LPM,which improves the solubility and bioavailability of LPM.The release rate is stable within 14 days,and no sudden release is observed,thus achieving sustained release.