Dipartimento Farmaco Chimico Tecnologico, Università degli Studi di Cagliari, Cagliari, Italy.
Eur J Pharm Biopharm. 2011 Nov;79(3):552-8. doi: 10.1016/j.ejpb.2011.07.005. Epub 2011 Jul 24.
In this paper, orally disintegrating tablets (ODT) were prepared using nanocrystal formulations in order to optimise dissolution properties of lipophilic, poorly soluble drug piroxicam (PRX). Different nanocrystal formulations were prepared using a high pressure homogenisation technique and poloxamer 188 as stabiliser. Characterisation of PRX nanocrystal ODT was carried out by infrared spectroscopy (FTIR), X-ray powder diffractometry (XRPD), differential scanning calorimetry and photon correlation spectroscopy. Dissolution study of PRX ODT was performed in distilled water (pH 5.5) and was compared to that of PRX coarse suspension ODT, PRX/poloxamer 188 physical mixture and bulk PRX samples. The XRPD and FTIR studies demonstrated that the homogenisation process led to a polymorphic transition from form I (bulk commercial PRX) to form III and monohydrate form of the nanocrystals. All ODT formulations prepared using PRX nanosuspensions showed a higher PRX dissolution rate compared with the ODT prepared with the coarse PRX. Since the solubility of the different PRX polymorphic forms increased only slightly from bulk PRX (form I) to monohydrate, form II and form III, we can conclude that the improvement in PRX dissolution rate is mainly caused by the increased surface-to-volume ratio due to the submicron dimension of the drug particles.
本文采用高压匀质技术制备纳米晶制剂，以优化脂溶性、难溶性药物吡罗昔康（PRX）的溶解性能。采用泊洛沙姆 188 作为稳定剂，制备了不同的纳米晶制剂。采用红外光谱（FTIR）、X 射线粉末衍射（XRPD）、差示扫描量热法和光子相关光谱对 PRX 纳米晶口崩片进行了表征。在去离子水（pH5.5）中进行了 PRX 口崩片的溶解研究，并与 PRX 粗混悬剂口崩片、PRX/泊洛沙姆 188 物理混合物和 PRX 原料药进行了比较。XRPD 和 FTIR 研究表明，匀质过程导致从 I 型（商业 PRX 原料药）向 III 型和纳米晶一水合物转变的多晶型转变。与使用粗 PRX 制备的口崩片相比，使用 PRX 纳米混悬剂制备的所有口崩片均显示出更高的 PRX 溶解速率。由于不同 PRX 多晶型的溶解度仅从 PRX 原料药（I 型）到一水合物、II 型和 III 型略有增加，因此我们可以得出结论，PRX 溶解速率的提高主要是由于药物颗粒的亚微米尺寸导致的比表面积增加所致。
