Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang, PR China.
Drug Dev Ind Pharm. 2010 Sep;36(9):1054-63. doi: 10.3109/03639041003642081.
The purpose of this study was to investigate the dissolution and oral bioavailability of an immediate-release tablet involving wet grinding of a poorly water-soluble drug, fenofibrate.
The milled suspension was prepared using a Basket Dispersing Mill in the presence of a hydrophilic polymer solution and then granulated with common excipients, and compressed into an immediate-release tablet with blank microcrystalline cellulose granules.
Compared with unmilled tablets (56% within 30 minutes), the dissolution of wet-milled tablets (about 98% in 30 minutes) was markedly enhanced. No significant decrease in the dissolution rate (96% in 30 minutes) of the wet-milled tablet was observed after 3 months under 40 degrees C and 75% relative humidity storage. In addition, the oral bioavailability of the wet-milled tablets (test) and Lipanthyl supra-bioavailability tablets (reference) was determined in beagle dogs after a single dose (160 mg fenofibrate) in a randomized crossover, own-control study. The results suggested that both the area under the plasma concentration-time curve (AUC((0-t)) = 46.83 +/- 11.09 microg/mL h) and the mean peak concentration of the test (C(max) = 4.63 +/- 1.71 microg/mL) were higher than the reference (AUC((0-t)) = 35.12 +/- 10.97 microg/mL h, C(max) = 2.11 +/- 0.08 microg/mL). The relative bioavailability of the wet-milled tablet was approximately 1.3-fold higher. Furthermore, the apparent rate of absorption of fenofibrate from the wet-milled tablet (T(max) = 2.63 hours) was faster than that from Lipanthyl (T(max) = 3.75 hours).
These results indicated that the dissolution and the bioavailability of fenofibrate were significantly enhanced by wet-grinding process. So, this shows that wet grinding is a powerful technique to improve the bioavailability for poorly water-soluble drugs, especially for Biopharmaceutics Classification System Class II compounds.
本研究旨在探讨涉及难溶性药物非诺贝特湿磨的即释片的溶出度和口服生物利用度。
在亲水性聚合物溶液存在的情况下，使用篮式分散磨制备研磨混悬液，然后用普通赋形剂造粒，并使用空白微晶纤维素颗粒压制成即释片。
与未研磨的片剂（30 分钟内 56%）相比，湿磨片剂的溶出度（30 分钟内约 98%）显著提高。在 40°C 和 75%相对湿度下储存 3 个月后，湿磨片剂的溶出速率（30 分钟内 96%）没有明显下降。此外，在一项随机交叉自身对照研究中，在比格犬中单剂量（160 毫克非诺贝特）给予湿磨片剂（试验）和 Lipanthyl 超高生物利用度片剂（对照）后，测定其口服生物利用度。结果表明，试验的血浆浓度-时间曲线下面积（AUC((0-t))=46.83±11.09μg/mL h）和平均峰值浓度（C(max)=4.63±1.71μg/mL）均高于对照（AUC((0-t))=35.12±10.97μg/mL h，C(max)=2.11±0.08μg/mL）。湿磨片剂的相对生物利用度约为 1.3 倍。此外，湿磨片剂中非诺贝特的表观吸收速率（T(max)=2.63 小时）快于 Lipanthyl（T(max)=3.75 小时）。
这些结果表明，湿磨工艺显著提高了非诺贝特的溶出度和生物利用度。因此，这表明湿磨是提高难溶性药物生物利用度的有效技术，特别是对生物药剂学分类系统 II 类化合物。
