Midha Kanav, Nagpal Manju, Singh Garima, Aggarwal Geeta
Chitkara College of Pharmacy, Chitkara University, Patiala, Punjab. India.
University School of Pharmaceutical Sciences, Rayat Bahra University - Pharmaceutics, Mohali, Punjab. India.
Curr Drug Deliv. 2017;14(8):1078-1096. doi: 10.2174/1567201813666160824123504.
More than 60% of the new drug molecules are lipophilic in nature. Low aqueous solubility and thus poor bioavailability is the main issue for these drugs for successful formulations into oral dosage form. Self-microemulsifying drug delivery systems (SMEDDS) have gained much attention. These are isotropic mixtures of different components (oil, surfactant and cosurfactant) that quickly disperse in gastrointestinal fluid yielding micro/nano-emulsions. These systems contain solubilized drug that is absorbed by lymphatic pathway along with other pathways like diffusion, collisional transfer, intracellular junctions, biliary acid pathway (BA), biliary acid mixed micelles pathway (BAMM) etc. and thus hepatic first pass metabolism is reduced. Stability of conventional SEDDS is considered very high with reference to other drug delivery systems as liposome, nanoparticles, nanoemulsion and micro emulsion. In fact SEDDS does not contain water in their composition which enhances their chemical and physical stability. Very few works have studied the stability of conventional SEDDS as it was confirmed. The major drawback for conventional SEDDS could be- i) high manufacturing cost (as they have to be filled in soft gelatin capsules); ii) interaction of capsule shell components with SEDDS. Therefore, attention has been given to transform liquid into solid SMEDDS by several techniques such as spray drying, spray cooling, super critical fluid technology and using adsorption carriers. Adsorption using solid carriers (Neusilin, Fujicalin, and dextran) is the successful inexpensive technique at initial research level whereas other requires expensive instrumentation.
Current review focuses on biopharmaceutical aspects, characterization of SMEDDS and excipients used in the formulation, techniques used for conversion of liquid SMEDDS to solid SMEDDS (including examples of various research reports where these techniques are used). Various adsorbent carriers (alongwith their different features) which have been reported in research papers have been detailed. It thoroughly covers patent literature on SMEDDS and research carried on solid SMEDDS as well which is the most imperative part of the review.
超过60%的新药分子本质上是亲脂性的。低水溶性以及由此导致的低生物利用度是这些药物成功制成口服剂型的主要问题。自微乳化药物递送系统(SMEDDS)受到了广泛关注。这些是不同成分(油、表面活性剂和助表面活性剂)的各向同性混合物,能在胃肠液中迅速分散形成微/纳米乳液。这些系统含有被溶解的药物,药物可通过淋巴途径以及其他途径(如扩散、碰撞转移、细胞间连接、胆汁酸途径(BA)、胆汁酸混合胶束途径(BAMM)等)被吸收,从而减少肝脏首过代谢。与脂质体、纳米颗粒、纳米乳液和微乳液等其他药物递送系统相比,传统SEDDS的稳定性被认为非常高。事实上,SEDDS的成分中不含水,这增强了它们的化学和物理稳定性。如已证实的那样,很少有研究关注传统SEDDS的稳定性。传统SEDDS的主要缺点可能是:i)制造成本高(因为它们必须填充在软胶囊中);ii)胶囊壳成分与SEDDS之间的相互作用。因此,人们通过喷雾干燥、喷雾冷却、超临界流体技术以及使用吸附载体等多种技术,致力于将液体转化为固体SMEDDS。在初始研究阶段,使用固体载体(硅铝酸盐、富吉胶和葡聚糖)进行吸附是一种成功且廉价的技术,而其他技术则需要昂贵的仪器设备。
当前综述聚焦于生物药剂学方面、SMEDDS的特性以及制剂中使用的辅料、将液体SMEDDS转化为固体SMEDDS所使用的技术(包括使用这些技术的各种研究报告实例)。已详细介绍了研究论文中报道的各种吸附载体(及其不同特性)。它全面涵盖了关于SMEDDS的专利文献以及对固体SMEDDS的研究,而这也是该综述最为关键的部分。