Gönüllü Umit, Uner Melike, Yener Gülgün, Altınkurt Turan
Istanbul University, Faculty of Pharmacy, Department of Pharmaceutical Technology, Beyazıt 34119 Istanbul, Turkey.
Int J Biomed Sci. 2006 Dec;2(4):337-43.
Opipramol 2-HCl (OP) is used for therapy of general somatoform and anxiety disorders. Conventional tablets in the market contain 50 mg OP to be used once or up to three times a day in effective treatment of depression in mild. In case of serious depressive disorders, OP may be administired up to 300 mg a day. Decrease in frequency of high dose administration via sustained drug release would reduce incidence of symptoms of intoxication in long-term use of OP. With this aim, OP matrix tablets containing 100 mg were prepared by direct compression method to be used once a day to provide patient compliance and constant blood level, consequently to decrease side effects. Two concentrations of polymers (10% and 20%): hydroxypropylcellulose (HPC) and hydroxypropyl methylcellulose (HPMC), sodium alginate (NaAlg), xanthan gum (XG) and Carbopol(®)941 (C941) were used in preparation of matrix tablets. Drug release study were performed in distilled water, pH1.2 HCl buffer and pH7.4 phosphate buffer solutions according to the Method II in USP 29. Two commercial tablets containing 50 mg OP available in Turkish market were used for comparison. Kinetic models of release patterns from tablets were evaluated. Drug release was displayed slower to faster pattern in order of formulations containing C941, HPMC and HPC. Drug release was significantly faster in tablets of 10% polymers than those of 20%. NaAlg and XG were insufficient to sustain drug release. The most sustaining drug release effect at the lowest polymer concentration was obtained with C941. Drug release from matrix tablets containing 10% C941 was determined as 58.2%, 52.4 and 57.0% in related dissolution mediums above after 8 hours, respectively. However, HPMC and HPC sustained drug release at 20% concentration. As a result, Carbopol® 941, HPMC and HPC can be suggested as suitable to prepare matrix tablets of OP.
盐酸奥匹哌醇（OP）用于治疗一般躯体形式障碍和焦虑症。市面上的传统片剂含有50毫克OP，用于轻度抑郁症的有效治疗，每日服用一次或最多三次。对于严重抑郁症，OP每日用量可达300毫克。通过持续释放药物降低高剂量给药频率，可减少长期使用OP时中毒症状的发生率。为此，采用直接压片法制备了含100毫克OP的基质片剂，每日服用一次，以提高患者依从性并维持恒定血药浓度，从而减少副作用。在基质片剂制备中使用了两种浓度（10%和20%）的聚合物：羟丙基纤维素（HPC）、羟丙基甲基纤维素（HPMC）、海藻酸钠（NaAlg）、黄原胶（XG）和卡波姆（®）941（C941）。根据美国药典29中的方法II，在蒸馏水、pH1.2盐酸缓冲液和pH7.4磷酸盐缓冲溶液中进行药物释放研究。使用土耳其市场上两种含50毫克OP的市售片剂进行比较。评估了片剂释放模式的动力学模型。含C941、HPMC和HPC的制剂的药物释放呈现出由慢到快的模式。10%聚合物片剂的药物释放明显快于20%聚合物片剂。NaAlg和XG不足以维持药物释放。在最低聚合物浓度下，C941具有最强的药物缓释效果。含10% C941的基质片剂在上述相关溶出介质中8小时后的药物释放率分别为58.2%、52.4%和57.0%。然而，HPMC和HPC在20%浓度下可维持药物释放。结果表明，卡波姆（®）941、HPMC和HPC适合制备OP基质片剂。
