Colombo G, Bortolotti F, Chiapponi V, Buttini F, Sonvico F, Invernizzi R, Quaglia F, Danesino C, Pagella F, Russo P, Bettini R, Colombo P, Rossi A
Department of Life Sciences and Biotechnology, University of Ferrara, Via Fossato di Mortara 17/19, 44121 Ferrara, Italy.
Department of Pharmacy, University of Parma, Parco Area delle Scienze 27/A, 43124 Parma, Italy.
Int J Pharm. 2016 Nov 30;514(1):229-237. doi: 10.1016/j.ijpharm.2016.07.002.
In this work nasal powder formulations of thalidomide were designed and studied to be used by persons affected by hereditary hemorrhagic telangiectasia as a complementary anti-epistaxis therapy, with the goal of sustaining the effect obtained with thalidomide oral treatment after its discontinuation for adverse effects. Three nasal powders were prepared using as carriers β-CD or its more hydrophilic derivatives such as hydropropyl-β-CD and sulphobutylether-β-CD and tested with respect to technological and biopharmaceutical features after emission with active and passive nasal powder devices. For all formulated powders, improved dissolution rate was found compared to that of the raw material, making thalidomide promptly available in the nasal environment at a concentration favouring an accumulation in the mucosa. The very limited transmucosal transport measured in vitro suggests a low likelihood of significant systemic absorption. The topical action on bleeding could benefit from the poor absorption and from the fact that about 2-3% of the thalidomide applied on the nasal mucosa was accumulated within the tissue, particularly with the β-CD nasal powder.
在本研究中,设计并研究了沙利度胺鼻用粉剂配方,供遗传性出血性毛细血管扩张症患者用作辅助性抗鼻出血治疗,目的是在因不良反应而停用沙利度胺口服治疗后维持其治疗效果。使用β-环糊精(β-CD)或其亲水性更强的衍生物(如羟丙基-β-环糊精和磺丁基醚-β-环糊精)作为载体,制备了三种鼻用粉剂,并通过主动和被动鼻用粉剂装置给药后,对其技术和生物药剂学特性进行了测试。对于所有配制的粉剂,与原料药相比,其溶出速率有所提高,使得沙利度胺能在鼻内环境中迅速以有利于在粘膜中蓄积的浓度出现。体外测得的经粘膜转运非常有限,表明全身显著吸收的可能性很低。对出血的局部作用可能得益于吸收不良以及应用于鼻粘膜的约2-3%的沙利度胺在组织内蓄积这一事实,尤其是使用β-CD鼻用粉剂时。