Department of Pharmaceutics and Industrial Pharmacy, Cairo University, Cairo, Egypt.
Eur J Pharm Biopharm. 2009 Sep;73(1):162-71. doi: 10.1016/j.ejpb.2009.04.005. Epub 2009 May 4.
Development of a lyophilized orally disintegrating tablet (ODT) that enhanced the in vitro dissolution and in vivo absorption of nimesulide (NM), a drug with poor solubility and poor bioavailability, is presented. The ODTs were prepared by freeze-drying an aqueous dispersion of NM containing a matrix former, a sugar alcohol, and a collapse protectant. In addition, different disintegration accelerators were tested. The influence of formulation parameters on the disintegration time and in vitro dissolution of NM from ODTs along with other tablet characteristics was investigated. Results obtained from disintegration and dissolution studies showed that lyophilized ODTs disintegrated within few seconds and showed significantly faster dissolution rate of NM compared to the plain powder drug and NM in commercially available immediate release tablet Sulide. The ODTs were also examined using differential scanning calorimetry, X-ray diffraction, and scanning electron microscope. Stability results, after 12-month storage of selected ODTs at 25 degrees C and 60% relative humidity, were satisfactory. The extent of absorption of NM from a selected ODT when compared to an conventional immediate release tablet as a reference after administration of 100mg oral dose of NM was determined in healthy subjects using a randomized crossover design. In this study, the rate of absorption of NM from ODT was faster than that from the reference tablet, had a significantly higher (p=0.012) peak plasma concentration, and shortened time to C(max) by 1h (p=0.029). The extent of absorption expressed by AUC was 62% larger when compared to the commercially available tablet.
本文介绍了一种冻干口腔崩解片（ODT）的研制，该 ODT 可提高尼美舒利（NM）的体外溶出度和体内吸收度。NM 的 ODT 是通过冷冻干燥含基质形成剂、糖醇和崩解抑制剂的 NM 水性分散体制备的。此外，还测试了不同的崩解促进剂。考察了处方参数对 ODT 崩解时间和 NM 体外溶出度的影响以及其他片剂特性。崩解和溶出研究结果表明，冻干 ODT 在数秒内崩解，与普通粉末药物和市售速释片 Sulide 中的 NM 相比，具有更快的 NM 溶解速率。还使用差示扫描量热法、X 射线衍射和扫描电子显微镜对 ODT 进行了检查。在 25°C 和 60%相对湿度下储存 12 个月后，选择的 ODT 的稳定性结果令人满意。在健康受试者中，使用随机交叉设计，比较了口服 100mg NM 后，与常规速释片作为参比，从选定的 ODT 中 NM 的吸收程度。在这项研究中，NM 从 ODT 的吸收速率比参比片剂快，具有显著更高的（p=0.012）峰血浆浓度，并将 C（max）时间缩短 1 小时（p=0.029）。与市售片剂相比，AUC 表示的吸收程度增加了 62%。
