Roda A, Sabatini L, Mirasoli M, Baraldini M, Roda E
Department of Pharmaceutical Sciences, University of Bologna, Via Belmeloro 6, 40126 Bologna, Italy.
Int J Pharm. 2002 Jul 8;241(1):165-72. doi: 10.1016/s0378-5173(02)00230-2.
A new sustained-release formulation (sustained release Ibifen) that gradually releases ketoprofen within 24 h and ensures therapeutic plasma concentration for the entire period has been developed. It consists of tableted pH-dependent barrier film-coated ketoprofen granules and was administered at a single dose of 200 mg to 12 volunteers. Ketoprofen plasma profiles were compared with: (1) administration of Orudis retard 200 capsule (200 mg); (2) two 12-h doses of prompt release Ibifen capsules (100 mg). In vitro dissolution kinetics and ketoprofen plasma levels were measured by HPLC. Sustained release Ibifen dissolution rate was constant for 10 h, whereas Orudis retard 200 dissolution profile presented one higher slope (0-6 h) and a lower one (6-12 h). Both formulations showed a delayed kinetics with respect to prompt release Ibifen. After sustained release Ibifen administration, ketoprofen plasma peak, reached within 2 h, remained practically constant for at least 12 h (average 4 microg/ml), which is higher than therapeutic levels. Differently, Orudis retard 200 produced a delayed, higher C(max) (5.91+/-0.66 vs. 4.51+/-0.65 microg/ml; P<0.01) and disappeared more quickly. In conclusion, sustained release Ibifen can ensure therapeutic ketoprofen plasma levels for the entire 24 h period, avoiding plasma concentration spikes, with bioavailability similar to other ketoprofen preparations.
一种新的缓释制剂（缓释异丁苯丙酸）已被研制出来，它能在24小时内逐渐释放酮洛芬，并在整个时间段确保治疗性血浆浓度。它由包有pH依赖性屏障膜的酮洛芬颗粒压制片组成，并以200毫克的单剂量给予12名志愿者。将酮洛芬的血浆曲线与以下情况进行比较：（1）服用奥鲁地斯缓释200胶囊（200毫克）；（2）分两次服用12小时剂量的速释异丁苯丙酸胶囊（100毫克）。通过高效液相色谱法测量体外溶出动力学和酮洛芬血浆水平。缓释异丁苯丙酸的溶出速率在10小时内保持恒定，而奥鲁地斯缓释200的溶出曲线呈现一个较高的斜率（0至6小时）和一个较低的斜率（6至12小时）。两种制剂相对于速释异丁苯丙酸均显示出延迟动力学。服用缓释异丁苯丙酸后，酮洛芬血浆峰在2小时内达到，至少在12小时内基本保持恒定（平均4微克/毫升），高于治疗水平。不同的是，奥鲁地斯缓释200产生延迟的、更高的C(max)（5.91±0.66对4.51±0.65微克/毫升；P<0.01）且消失得更快。总之，缓释异丁苯丙酸可在整个24小时期间确保治疗性酮洛芬血浆水平，避免血浆浓度峰值，其生物利用度与其他酮洛芬制剂相似。
