Revankar S N, Bhatt A D, Desai N D, Bolar H V, Sane S P, Tipnis H P
Novartis India Limited, Goregaon (E), Mumbai.
J Assoc Physicians India. 1999 Sep;47(9):886-9.
To assess the bioquivalence of carbamazepine (CBZ) controlled release formulation A (Tegretol CR, local) vs formulation B (Tegretol CR, Basel) and confirm their controlled release characteristics by comparing with conventional formulation (Tegretol).
A three-way randomized cross-over bioavailability study was carried out using CBZ 200 mg tablets of conventional and two controlled release formulations in twelve healthy volunteers. Coded plasma samples were analysed for levels of CBZ by HPLC method.
The mean Cmax, Tmax, t1/2 and AUC for formulation A were: 1.67 +/- 0.26 mcg/mL, 24 +/- 0 hr, 47.8 +/- 9.7 hr and 136.7 +/- 25.4 mcg/ml. h; for formulation B were 1.41 +/- 0.31 mcg/mL, 25 +/- 8 hr, 46.9 +/- 7.9 and 119 +/- 32.3 mcg/ml.h and for conventional formulation were 2.43 +/- 3.6 mcg/mL, 9.5 +/- 7.4 hr, 44.6 +/- 9.8 hr and 178.8 +/- 41.9 mcg/ml.h respectively. The fluctuation in plasma concentration within 24 h (peak:trough) were 11.7 +/- 8.14% with conventional formulation as compared to 0% and 1.2 +/- 3.98% with formulation A and B respectively. The mean Tmax for both the controlled release formulations was not statistically significant. On the basis of 90% confidence interval, mean AUC and Cmax values obtained after controlled release formulation A, though statistically significant (P < 0.05) lie well within the prescribed limits of 80-120% as compared to formulation B. Thus both the controlled release formulations were bioequivalent. In comparison to conventional formulation, both controlled release formulations gave lower Cmax, lower AUCs, higher Tmax values, less fluctuation in CBZ plasma concentrations, reduction in ratio of Cmax/AUC values, thus demonstrating controlled release characteristics of the formulation.
Based on the above mentioned parameters both controlled release formulations are bioequivalent and demonstrate controlled release characteristics.
评估卡马西平（CBZ）控释制剂A（得理多控释片，本地）与制剂B（得理多控释片，巴塞尔）的生物等效性，并通过与传统制剂（得理多）比较来确认它们的控释特性。
在12名健康志愿者中使用传统的200 mg卡马西平片以及两种控释制剂进行了一项三交叉随机生物利用度研究。通过高效液相色谱法对编码的血浆样本进行卡马西平水平分析。
制剂A的平均Cmax、Tmax、t1/2和AUC分别为：1.67±0.26 mcg/mL、24±0小时、47.8±9.7小时和136.7±25.4 mcg/ml·h；制剂B分别为1.41±0.31 mcg/mL、25±8小时、46.9±7.9小时和119±32.3 mcg/ml·h；传统制剂分别为2.43±3.6 mcg/mL、9.5±7.4小时、44.6±9.8小时和178.8±41.9 mcg/ml·h。传统制剂在24小时内血浆浓度的波动（峰：谷）为11.7±8.14%，而制剂A和B分别为0%和1.2±3.98%。两种控释制剂的平均Tmax无统计学差异。基于90%置信区间，与制剂B相比，控释制剂A获得的平均AUC和Cmax值虽有统计学意义（P<0.05），但均在规定的80 - 120%范围内。因此，两种控释制剂具有生物等效性。与传统制剂相比，两种控释制剂的Cmax较低、AUC较低、Tmax值较高、卡马西平血浆浓度波动较小、Cmax/AUC值的比值降低，从而证明了制剂的控释特性。
基于上述参数，两种控释制剂具有生物等效性并表现出控释特性。
