Study On Synthesis,Characterization And Properties Of Penciclovir Cocrystals

Drugs are essential to the health and life of the people.In recent years,with the rising incidence of major diseases,new drug research and development and drug production have received increasing attention from the government and pharmaceutical companies.Among them,study on the improvement of the solubility of poorly soluble drugs has always been a key issue in drug development.The low solubility of poorly soluble drugs will lead to a decrease in the dissolution rate of the drugs,which will affect the absorption of the drugs.Therefore,improving the water solubility of drugs is the key to exactly ensure the efficacy of drugs.In recent years,it has been reported that solid drugs can be prepared as cocrystals to increase their water solubility,thereby improving the therapeutic effect.A drug cocrystal refers to a crystal formed by combining an active pharmaceutical ingredient with a cocrystal coformer at a fixed stoichiometric ratio using non-covalent interactions.It is an effective method to improve the water solubility of solid drugs.Penciclovir is a broad-spectrum nucleoside antiviral drug that inhibits viruses such as HSV-Ⅰ,HSV-Ⅱ,HBV,EBV,and CMV.Penciclovir has poor water solubility.Thus it is difficult to be absorbed orally and is also not easy to make liquid preparations such as injections and eye drops.Therefore we attempted to prepare cocrystals to improve the solubility of penciclovir,which is of particular significance for the development of oral and liquid formulations of penciclovir.In this thesis,penciclovir was screened for cocrystals by grinding method,and seven cocrystals with 4-hydroxybenzoic acid,3,5-dihydroxybenzoic acid,gallic acid,and 4-hydroxylcinnamic acid were prepared by suspension method.The cocrystals were characterized by single crystal X-ray diffraction analysis,powder X-ray diffraction analysis,thermogravimetric analysis,differential thermal scanning calorimetry,infrared spectroscopy and other techniques.The powder and intrinsic dissolution experiments of the cocrystals in a phosphate buffer solution with a p H of 7.4 were carried out.The dynamic vapor sorption measurements and the accelerated ICH condition tests of all cocrystals were also performed.The results showed all cocrystals were stable enough to endure standard processing step.The solubility of the anhydrous cocrystal of penciclovir and 3,5-dihydroxybenzoic acid was significantly improved compared to the pure penciclovir.This study provides a research basis for the development of penciclovir oral and liquid preparations of penciclovir..