Bruni Giovanna, Maggi Lauretta, Tammaro Loredana, Lorenzo Rosadele Di, Friuli Valeria, D Aniello Sharon, Maietta Mariarosa, Berbenni Vittorio, Milanese Chiara, Girella Alessandro, Marini Amedeo
C.S.G.I. - Department of Chemistry, Physical-Chemistry Section, University of Pavia, Viale Taramelli 16, 27100 Pavia, Italy.
Department of Drug Sciences, University of Pavia, Viale Taramelli 12, 27100 Pavia, Italy.
Int J Pharm. 2016 Sep 10;511(1):190-197. doi: 10.1016/j.ijpharm.2016.07.011. Epub 2016 Jul 11.
Solubility represents an important challenge for formulation of drugs, because the therapeutic efficacy of a drug depends on the bioavailability and ultimately on its solubility. Low aqueous solubility is one of the main issues related with formulation design and development of new molecules. Many drug molecules present bioavailability problems due to their poor solubility. For this reason there is a great interest in the development of new carrier systems able to enhance the dissolution of poorly water-soluble drugs. In this work, fibers containing an insoluble model drug and prepared by an electrospinning method, are proposed and evaluated to solve this problem. Two hydrophilic polymers, polyvinylpyrrolidone (Plasdone® K29/32) and polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus®) were used to increase the water solubility of perphenazine. The physico-chemical characterization suggests that the drug loaded in the fibers is in the amorphous state. Both polymeric carriers are effective to promote the drug dissolution rate in water, where this active pharmaceutical ingredient is insoluble, due to the fine dispersion of the drug into the polymeric matrices, obtained with this production technique. In fact, the dissolution profiles of the fibers, compared to the simple physical mixture of the two components, and to the reference commercial product Trilafon® 8mg tablets, show that a strong enhancement of the drug dissolution rate can be achieved with the electrospinning technique.
溶解度是药物制剂面临的一项重要挑战，因为药物的治疗效果取决于生物利用度，最终取决于其溶解度。低水溶性是新分子制剂设计与开发相关的主要问题之一。许多药物分子由于溶解度差而存在生物利用度问题。因此，开发能够提高难溶性药物溶出度的新型载体系统备受关注。在这项工作中，提出并评估了通过静电纺丝法制备的含有不溶性模型药物的纤维，以解决这一问题。使用两种亲水性聚合物，聚乙烯吡咯烷酮（Plasdone® K29/32）和聚乙烯己内酰胺-聚醋酸乙烯酯-聚乙二醇接枝共聚物（Soluplus®）来提高奋乃静的水溶性。物理化学表征表明，负载在纤维中的药物处于无定形状态。由于通过这种生产技术使药物在聚合物基质中得到精细分散，这两种聚合物载体均能有效提高该难溶性活性药物成分在水中的溶出速率。事实上，与两种成分的简单物理混合物以及参比市售产品Trilafon® 8mg片剂相比，纤维的溶出曲线表明，静电纺丝技术能够显著提高药物的溶出速率。
