결정다형이 아목시실린의 상대적 생체이용률에 미치는 영향

The Effects of Pseudopolymorphism on the Relative Bioavailability of Amoxicillin

Four different pseudopolymorphs of amoxicilline-trihydrate, dihydrate, monohydrate and anhydrate were prepared and characterized by UV spectrophotometry, DSC, and TGA. In vitro dissolution studies of four pseudopolymorphs were carried out in pH 6.8 phosphate buffer at 37oC by means of a rotating disk method. The effect of four pseudopolymorphs on bioavailability of amoxicillin was studied in healthy 6 subjects using urinary excretion method. The dissolution result was shown in the sequence, trihydrate(95.5%)>monohydrate(83.5%)>anhydrate(67.6%)>dihydrate(15.8%). The urinary excretion rate of anhydrate could not be detected and the dissolution results agreed well with in vivo pharmacokinetic study results. The effects of storage, conditions, milling and compression on the pseudopolymorphic transformation were investigated by thermal methods. The results showed that four pseudopolymorphs were not transformed and they were very stable.