Wu Baojian, Shun Ningyun, Wei Xiuli, Wu Wei
Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, China.
Pharm Dev Technol. 2007;12(2):203-10. doi: 10.1080/10837450601168722.
Hydrogel compression-coated tablets are able to release the core drug after a period of lag time and have potential for colon-specific drug delivery based on gastrointestinal transit time concept. This study investigated the factors influencing in vitro release characteristics of a model drug 5-fluorouracil from hydroxypropylmethycellulose (HPMC) compression-coated tablets. The core tablet, prepared by a wet granulation compression method, was designed to disintegrate and dissolute quickly. To prepare the compression-coated tablets, 50% of the HPMC/lactose coat powder was precompressed first, followed by centering the core tablet and compressing with the other 50% of the coat powder. Release characteristics were evaluated in distilled water by using a Chinese Pharmacopoeia rotatable basket method. Effect of HPMC viscosity, lactose content in outer shell, and overall coating weight of outer shell on release lag time (T(lag)), and zero-order release rate (k) were studied. Release of drug from compression-coated tablets began after a time delay as a result of hydrogel swelling/retarding effect, followed by zero-order release for most of the formulations studied. HPMC of higher viscosity (K4M and K15M) provided better protection of the drug-containing core, showing increased release lag time and slower release rate. Incorporating lactose in outer shell led to decrease of T(lag) and increase of k. T(lag) and k are exponentially and linearly correlated to lactose content, expressed as weight percentage of the outer shell. Larger coating weight (W) of outer shell produced larger coating thickness (D) around core tablet, which resulted in increase in T(lag) and decrease in k. There was good fitting of a linear model for each of the four variables W, D, T(lag), and k. Hardness of the compression-coated tablets and pHs of the release media had little effect on drug release profile. It is concluded that the release lag time and release rate are able to be tailored through adjusting the formulation variables to achieve colon-specific drug delivery of 5-fluorouracil.
水凝胶包衣压制片能够在一段滞后时间后释放核心药物，并且基于胃肠道转运时间概念具有结肠特异性给药的潜力。本研究考察了影响模型药物5-氟尿嘧啶从羟丙基甲基纤维素（HPMC）包衣压制片中体外释放特性的因素。采用湿法制粒压片法制备的核心片设计为能快速崩解和溶解。为制备包衣压制片，先预压50%的HPMC/乳糖包衣粉，然后将核心片居中，再用另外50%的包衣粉进行压制。采用中国药典转篮法在蒸馏水中评价释放特性。研究了HPMC粘度、外层乳糖含量和外层总包衣重量对释放滞后时间（T(lag)）和零级释放速率（k）的影响。由于水凝胶溶胀/阻滞作用，包衣压制片中药物的释放在经过一段时间延迟后开始，随后在所研究的大多数制剂中呈现零级释放。较高粘度的HPMC（K4M和K15M）能更好地保护含药核心，表现出释放滞后时间延长和释放速率减慢。在外层中加入乳糖导致T(lag)降低和k增加。T(lag)和k与乳糖含量呈指数和线性相关，乳糖含量以占外层重量的百分比表示。外层较大的包衣重量（W）在核心片周围产生较大的包衣厚度（D），这导致T(lag)增加和k降低。对于四个变量W、D、T(lag)和k中的每一个，线性模型拟合良好。包衣压制片的硬度和释放介质的pH值对药物释放曲线影响很小。得出结论，通过调整制剂变量可以调节释放滞后时间和释放速率，以实现5-氟尿嘧啶的结肠特异性给药。
