Ambrogi V, Perioli L, Marmottini F, Giovagnoli S, Esposito M, Rossi C
Dipartimento di Chimica e Tecnologia del Farmaco, Via del liceo 1, Perugia, Italy.
Eur J Pharm Sci. 2007 Nov;32(3):216-22. doi: 10.1016/j.ejps.2007.07.005. Epub 2007 Aug 6.
The aim of the present paper was the use of mesoporous silicate MCM-41 to increase the dissolution rate of piroxicam, a non-steroidal anti-inflammatory drug-class II of the Biopharmaceutic Classification System. The inclusion/adsorption compound of piroxicam in MCM-41 was obtained with a drug loading of about 14%. X-ray powder diffraction and differential scanning calorimetry (DSC) revealed the presence of piroxicam not arranged in crystalline form and FT-IR spectroscopy showed the presence of light interactions (hydrogen bonds) between the silicate silanols and the drug. The decrease of Brunauer, Emmett and Teller (B.E.T.) specific surface area and pore volume between free MCM-41 and the inclusion/adsorption compound was a prove of the presence of piroxicam inside the mesopores. The inclusion compound was submitted to in vitro dissolution tests and a remarkable dissolution rate improvement was observed in comparison to the crystalline drug in all tested conditions. The dissolution profile at pH 1.2 was comparable to that of the marketed product Brexin, a formulation with rapid analgesic effect onset. The improvement of dissolution rate is due to both the lack of drug in the crystalline form and to the extremely large surface area of the siliceous support. Physical stability tests of the free drug and the inclusion/adsorption complex were conducted as well over one month storage at 40 degrees C at different relative humidity.
本论文的目的是使用介孔硅酸盐MCM-41来提高吡罗昔康的溶解速率，吡罗昔康是生物药剂学分类系统中的II类非甾体抗炎药。吡罗昔康在MCM-41中的包合/吸附化合物的载药量约为14%。X射线粉末衍射和差示扫描量热法（DSC）显示存在非结晶形式的吡罗昔康，傅里叶变换红外光谱（FT-IR）表明硅酸盐硅醇与药物之间存在微弱相互作用（氢键）。游离MCM-41与包合/吸附化合物之间的布鲁诺尔、埃米特和泰勒（B.E.T.）比表面积及孔体积的减小证明了介孔内存在吡罗昔康。对包合化合物进行了体外溶出试验，结果表明在所有测试条件下，与结晶药物相比，其溶出速率均有显著提高。在pH 1.2时的溶出曲线与市售产品布雷辛（Brexin）相当，布雷辛是一种起效迅速的镇痛制剂。溶出速率的提高归因于药物不存在结晶形式以及硅质载体的极大表面积。还对游离药物和包合/吸附复合物在40℃、不同相对湿度下储存一个多月进行了物理稳定性测试。
