장용성 란소프라졸 캅셀의 제조 및 생물학적 동등성 시험 = Preparation and Bioequivalence Test of Enteric Coated Lansoprazole Capsule

다국어 초록 (Multilingual Abstract)

Iansoprazole, (H+/K+)-ATPase (proton pump) inhibitor is being widely used to gastro-intestinal peptic ulcer patients. Koryo Pharmaceutical Company tried to develope lansoprazole capsule bioeqivalent to already being marketed lansoprazole capsule, reference product, which is producted by Hanil Pharmaceutical Company. Through in vitro dissolution tests of preformulated test capsules (Test capsule A, B, C and D) compared with reference, one capsule (Test capsule D) compared with reference, one capsule (Test capsule D) was selected which had a very similar dissolution profile as reference. And bioequivalence test in human volunteers was conducted to obtain marketing approvement of test capsule D. Dissolution tests of preformulated products were conducted in dissolution solution I (acid solution, pH 1.2) by dissolution method Ⅱ(paddle method) (KP Ⅵ) for 60 minutes, and then followed in dissolution solution Ⅱ(phosphate buffer, pH 6.8) by dissolution method Ⅰ (basket method) (KP Ⅵ) for 60 minutes. The dissolution solutions was maintained at 37±0.5℃, and basket and paddle were rotated at 150± 5 rpm, respectively. Also, in bioequivalence test, 14 healthy male volunteers were administered one capsule of test capsule(30 ㎎ lansoprazole/cap, Koryo Pharm. Co.) or reference, and randomized two-period, cross-over study was applied. Bioequivalence was statistically analyzed between two products using pharmacokinetic parameters (AUC, C_(max) and T_(max)). The results showed that the differences in AUC, C_(max) and T_(max) between two products were 8.75%, 9.32% and 29.79%, respectively. Detectable (△) of AUC, C_(max) ands T_(max) were 15.79％, 18.18％ and 45.17％, at α=0.1 and power (1-β)=0.8, respectively, and also confidence intervals were -1.91％ ≤△≤ 19.41％, -2.96％ ≤△≤21.59％ and -0.70％≤△≤60.28％, respectively. Among pharmacokinetic parameters, AUC met the criteria of KFDA for bioequivalence, while T_(max) and C_(max) didn't meet exactly the criteria of KFDA. But lansoprazole is medicated for long term, and C_(max) did't meet exactly the criteria of KFDA. But lansoprazole is medicated for long term, and absorption amount is more important rather than absorption rate. So considering on clinical aspects of lansoprzole, it was concluded that test capsule, Lansid^(R), is bioequivalent to reference, Lanston^(R) capsule by KFDA.