Study And Preparation Of Chloral Hydrate Suppository

Chloral hydrate is 2,2,2-trichloro-1,1-ethylene glycol,a colorless transparent crystalline solid with pungent odor and bitter taste.The addition of three chlorine atoms can increase the liposolubility of acetalde hyde and in hibit the central nervous system.It can cause similar physiological sleep wit hout obvious aftereffect.Up to now,only one pharmaceutical company has declared chloral hydrate enema in China.Chloral hydrate suppository and chloral hydrate enema have been listed in Japan.The chloral hydrate suppository produced by Jiuguang Pharmaceutical Co.,Ltd.in Japan has the advantage of dosage.It can improve compliance in children compared with oral liquid.Meanwhile,it is easier to use than enema with higher drug absorption.This suppository is actually a soft capsule,also known as rectal capsule.It is used for sedation and hypnosis during physical examination,and also for patients with spastic state of intravenous injection.The preparation has not been approved for market in C hina.This article mainly imitates the chloral hydrate suppository made in Japan,ai ming to make it domestically as soon as possible and to be used in clinic for the convenience of patients.This paper imitates chloral hydrate suppositories,which belong to three categories of chemical drugs.According to the requirements for registration and declaration of chemical drugs issued by the State Food and Drug Administration,and the relevant information recorded in the preparation instructions and retrieval literature of Pharmaceutical Data in Japan,chloral hydrate suppositories will be studied meanwhile in combination with the Pharmacopoeia standards of similar preparations in various countries.The purpose is to accumulate information for the registration of chloral hydrate suppositories.Its research contents mainly include the following parts:The stage of original research quality research:the chloral hydrate suppository produced by Japanese Jiuguang Pharmaceutical Company is only listed in Japanese company,not in t he United States,China and other European countries without relevant quality standards.Therefore,this paper first carries on the research and analysis of the original preparation,which deepens the understanding of the product and summarizes the quality of the product.Finally,this paper species the key quality attributes to guide the development of subsequent prescriptions and processes.Prescription development:Based on the analysis of the prescription of original preparation,the generic preparation use the same excipients as original preparation.According to the properties of raw materials and excipients and the analysis results of original preparations,the effects of materials on the key quality attributes of products were evaluated,and the prescriptions of capsule shell and contents were screened respectively.Finally,the prescription composition was determined by comparing with the quality characteristics of the original preparation.Process development:Based on the common process of soft capsule,the influence of process on the key quality attributes of products was evaluated.Finally,the pretreatment of raw materials and excipients,the preparation of capsule glue solution,heat preservation,preparation of content liquid,were determined.The process parameters of pilling,shaping,drying were screened and confirmed.Eatablish methods:A method for the determination of chloral hydrate was established.A method for the determination of the related substances in chloral hydrate suppositories was established.A liquid phase method was developed for the determination of preservatives in chloral hydrate suppositories.Pharmacodynamic evaluation of chloral hydrate suppositories:The pharmacodynamics and pharmacokinetics in rabbit were performed with chloral hydrate suppository as self-made group and ESCRE as original group.The results s howed t hat the effect of self-made group and original group both can last about one hour,and the action time of self-made preparation was earlier than that of original preparation.The pharmacokinetic experiments showed that the relative bioavailability of the self-made preparation was 85.67%.The formulation of the self-made preparation should be optimized to get higher bioavailability.The rectal irritation test showed that the local inflammation of the original preparation was more serious than that of the self-made preparation.