Department of Pharmaceutical Technology and Raw Materials Development, National Institute for Pharmaceutical Research and Development, Abuja, Nigeria.
Acta Pharm. 2012 Mar;62(1):71-82. doi: 10.2478/v10007-012-0001-6.
Sustained release (SR) dosage forms enable prolonged and continuous deposition of the drug in the gastrointestinal (GI) tract and improve the bioavailability of medications characterized by a narrow absorption window. In this study, a new strategy is proposed for the development of SR dosage forms for theophylline (TPH). Design of the delivery system was based on a sustained release formulation, with a modified coating technique and swelling features aimed to extend the release time of the drug. Different polymers, such as Carbopol 71G (CP), sodium carboxymethylcellulose (SCMC), ethylcellulose (EC) and their combinations were tried. Prepared matrix tablets were coated with a 5 % (m/m) dispersion of Eudragit (EUD) in order to get the desired sustained release profile over a period of 24 h. Various formulations were evaluated for micromeritic properties, drug concentration and in vitro drug release. It was found that the in vitro drug release rate decreased with increasing the amount of polymer. Coating with EUD resulted in a significant lag phase in the first two hours of dissolution in the acidic pH of simulated gastric fluid (SGF) due to decreased water uptake, and hence decreased driving force for drug release. Release became faster in the alkaline pH of simulated intestinal fluid (SIF) owing to increased solubility of both the coating and matrixing agents. The optimized formulation was subjected to in vivo studies in rabbits and the pharmacokinetic parameters of developed formulations were compared with the commercial (Asmanyl(®)) formulation. Asmanyl(®) tablets showed faster absorption (t(max) 4.0 h) compared to the TPH formulation showing a t(max) value of 8.0 h. The C(max) and AUC values of TPH formulation were significantly (p < 0.05) higher than those for Asmanyl(®), revealing relative bioavailability of about 136.93 %. Our study demonstrated the potential usefulness of eudraginated polymers for the oral delivery of the sparingly soluble drug theophylline.
缓释（SR）剂型能够使药物在胃肠道（GI）中长时间持续沉积，提高吸收窗狭窄的药物的生物利用度。在这项研究中，提出了一种茶碱（TPH）缓释剂型的新策略。设计给药系统基于缓释制剂，采用改良的涂层技术和溶胀特性，以延长药物的释放时间。尝试了不同的聚合物，如 Carbopol 71G（CP）、羧甲基纤维素钠（SCMC）、乙基纤维素（EC）及其组合。制备的基质片剂用 5%（m/m）的 Eudragit（EUD）分散体包衣，以获得 24 小时内所需的持续释放曲线。对各种制剂进行了微粉学性质、药物浓度和体外药物释放的评价。结果发现，随着聚合物用量的增加，体外药物释放速率降低。EUD 包衣在模拟胃液（SGF）的酸性 pH 下的前两个小时内，由于水合作用减少，药物释放的驱动力降低，导致药物释放速度显著减慢。在模拟肠液（SIF）的碱性 pH 下，由于涂层和基质化剂的溶解度增加，释放速度加快。优化的制剂在兔体内进行了研究，并将开发制剂的药代动力学参数与商业（Asmanyl（®））制剂进行了比较。Asmanyl（®）片剂的吸收速度较快（t（max）为 4.0 h），而 TPH 制剂的 t（max）值为 8.0 h。TPH 制剂的 C（max）和 AUC 值明显（p < 0.05）高于 Asmanyl（®），表明相对生物利用度约为 136.93%。我们的研究表明，Eudragit 聚合物在难溶性药物茶碱的口服给药中具有潜在的应用价值。
