Synthesis And Properties Of PH-Sensitive Hydroxypropylmethylcellose Derivatives

Thin-film coating technology is commonly used in the controlled-or sustained-release of oral drugs.In recent years,It has also been used for colon-specific drug delivery to improve the treatment effects of colon diseases,to reduce systemic side effects,to avoid the drugs,such as protein peptide,being destructed in the gastrointestinal tract and hence improve their bioavailability.In this thesis,pH-senstives hydroxypropylmethylcellose(HPMC)derivatives were designed and synthesized for use as novel oral colon-specific coating agents.Two types of HPMC were chemically modified,using acetic anhydride(AA)and tetrahydrophthalic anhydride(THPA)or methyltetrahydrophthalic anhydride(MTHPA)or hexahydrophthalic anhydride(HHPA) or methylhexahydrophthalic anhydride(MHHPA)or nadic anhydride(NA),to obtain pH-sensitive polymers,hydroxypropylmethylcellose acetate tetrahydrophtalate (HPMCATH),hydroxypropylmethylcellose acetate methyltetrahydrophtalate (HPMCAMT),hydroxypropylmethylcellose acetate hexahydrophthalate(HPMCAHH), hydroxypropylmethylcellose acetate methylhexahydrophthalate(HPMCAMH), hydroxypropylmethylcellose acetate nadicate(HPMCANA).The new polymers were characterized by infrared spectroscopy,determination of acetyl content and acid value.Their pharmaceutical properties,such as pH-sensitive values,water vapor permeability,tensile strength and glass temperature(Tg),were investigated and compared with those of methylcellulose acetate succinate(HPMCAS).The structure-property relationship was preliminarily discussed.HPMCAMT-15, HPMCAP-10 and HPMCANA-10 have good film-forming nature.Their pH-sensitive values were 6.6-7.2,5.5-6.2 and 4.7-5.3 respectively.In vitro release experiment using diclofanac sodium tablets as model drug was done.The results demonstrate that HPMCAMT-15-4 could compeletly suppress drug release within 2h in 0.1mol/L hydrochloric acid.Tablets coated with HPMCAMT-15-4 hardly release drug within 3h in pH=6.8 buffer solution,while they rapidly release drug in pH=7.2 buffer solution.HPMCAMT-15-4 may be a useful matieral for a novel oral colon-specific drug delivery system.