Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Pharm Dev Technol. 2010 Mar-Apr;15(2):139-53. doi: 10.3109/10837450903059371.
The short half-life of lornoxicam, a potent non-steroidal anti-inflammatory drug, makes the development of sustained-release (SR) forms extremely advantageous. However, due to its weak acidic nature, its release from SR delivery systems is limited to the lower gastrointestinal tract which consequently leads to a delayed onset of its analgesic action. Accordingly, the aim of this study was to develop lornoxicam SR matrix tablets that provide complete drug release that starts in the stomach to rapidly alleviate the painful symptoms and continues in the intestine to maintain protracted analgesic effect as well as meets the reported SR specifications. The proposed strategy was based on preparing directly compressed hydroxypropylmethylcellulose matrix tablets to sustain lornoxicam release. Basic pH-modifiers, either sodium bicarbonate or magnesium oxide, were incorporated into these matrix tablets to create basic micro-environmental pH inside the tablets favorable to drug release in acidic conditions. All the prepared matrix tablets containing basic pH-modifiers showed acceptable physical properties before and after storage. Release studies, performed in simulated gastric and intestinal fluids used in sequence to mimic the GI transit, demonstrate the possibility of sustaining lornoxicam release by combining hydrophilic matrix formers and basic pH-Modifiers to prepare tablets that meet the reported sustained-release specifications.
洛索洛芬是一种强效的非甾体抗炎药,其半衰期较短,因此开发其缓释(SR)剂型具有极大的优势。然而,由于其弱酸性性质,其从 SR 给药系统中的释放仅限于下胃肠道,这导致其镇痛作用的起效时间延迟。因此,本研究的目的是开发洛索洛芬 SR 基质片剂,使其在胃中开始完全释放,从而迅速缓解疼痛症状,并在肠道中持续释放,以维持长期的镇痛效果,同时满足已报道的 SR 规范。所提出的策略基于制备直接压缩羟丙甲纤维素基质片剂来持续释放洛索洛芬。将碱性 pH 调节剂(碳酸氢钠或氧化镁)掺入这些基质片剂中,以在片剂内部形成有利于在酸性条件下药物释放的碱性微环境 pH。所有含有碱性 pH 调节剂的制备好的基质片剂在储存前后均表现出可接受的物理性质。在模拟胃肠道的连续使用的胃液和肠液中的释放研究表明,通过将亲水基质形成剂和碱性 pH 调节剂相结合来制备满足报道的缓释规范的片剂,可以实现洛索洛芬的持续释放。