Chemical Modification Of Hydroxypropyl Methylcellulose And Performance Of Its Aqueous Films

Hydroxypropyl methylcellulose（HPMC）is a high-quality pharmaceutical excipient prepared by etherification of alkali cellulose.There are a large number of active hydroxyl groups on its polymer chain,so it can be further chemically modified.Hydroxypropyl methylcellulose acetate succinate（HPMCAS）,as one of the esterification products of HPMC,has ionizable terminal carboxyl groups,enabling it to exist stably in acidic environment and rapidly dissolve in alkaline environment.Therefore,HPMCAS can be used as an enteric coating material for specific drugs to prevent the drug from dissolving in the stomach in advance and to protect the gastric mucosa from being stimulated by the drugs.After the drug reaches the intestine,the internal active ingredients are released for optimal absorption effect.Therefore,HPMCAS has important practical and theoretical potential.In this thesis,HPMC is used as the raw material,acetic anhydride and succinic anhydride are used as the esterifying agent,and anhydrous sodium acetate is used as the catalyst,HPMCAS is synthesized in acetic acid.The effects of different esterification conditions on the end groups content of HPMCAS and on physiochemical/mechanical properties of HPMCAS aqueous films are studied.The results show that the reaction temperature and the addition ratio of esterifying agent have a greater effect on the end group content.Increasing the content of succinyl will cause the increase of tensile strength and the decrease of initial dissolution p H value of HPMCAS aqueous films.However,too much succinyl content will also decrease the tensile strength of HPMCAS aqueous film.Under the optimal reaction conditions,the dissolution p H value of HPMCAS aqueous film is 5.2,and the tensile strength at break is 55 MPa,which meets the performance requirements of enteric coating materials.In order to further investigate the performance of the HPMCAS aqueous films,HPMCAS with a specific end group content is selected as the raw material.The mechanical properties,p H solubility of HPMCAS aqueous films and stability of aqueous HPMCAS solution under different types of neutralizers and different degrees of neutralization are studied.The results show that when NH₄OH and NH₄HCO₃ are used as neutralizers and are excessively neutralized,the tensile strength and elongation at break of the HPMCAS aqueous films can reach 52 MPa and 20%,respectively.And the dissolution p H of HPMCAS films is 5.2.Besides,the aqueous HPMCAS solution maintain stable for at least one month.The preparation method of HPMCAS aqueous films used in this paper is simple and efficient,and the raw materials can be larger particles,and this method does not include any additives such as emulsifiers or plasticizers.We hope this research will contribute to develop aqueous HPMCAS enteric coating formulation with superior performances.