不同灭菌方法对生物粘附性粉末和眼用微型片性质的影响及临床评价

Effect of different sterilisation methods on the properties of bioadhesive powders and ocular minitablets, and clinical evaluation.

作者信息

Weyenberg W, Vermeire A, D'Haese E, Vanhaelewyn G, Kestelyn P, Callens F, Nelis H J, Remon J P, Ludwig A

机构信息

Laboratory of Pharmaceutical Technology and Biopharmacy, University of Antwerp, Universiteitsplein 1, B-2610 Antwerp, Belgium.

出版信息

Eur J Pharm Sci. 2004 Sep;23(1):77-87. doi: 10.1016/j.ejps.2004.05.010.

DOI:10.1016/j.ejps.2004.05.010

PMID:15324925

Abstract

The purpose of this study was to evaluate the influence of gamma-irradiation and dry heat sterilisation on the properties of a bioadhesive powder mixture containing ciprofloxacin and its corresponding ocular minitablets. The molecular weight characteristics of drum dried waxy maize starch (DDWM), employed as major component of the bioadhesive formulation, the decay kinetics of radicals, the rheological properties of the bioadhesive polymers and the microbial activity of ciprofloxacin were studied. The influence of the different sterilisation methods on the characteristics of the ocular minitablets was investigated by measuring the crushing strength, the friability, and the in vitro release of ciprofloxacin from the minitablets. Finally, the clinical value of the selected sterilised minitablets was evaluated in seven healthy volunteers. Both sterilisation methods similarly affected the properties of the bioadhesive formulation by inducing stable radicals and decreasing the molecular weight of DDWM, although no changes in the microbiological activity of ciprofloxacin were measured. An obvious influence of both sterilisation methods was observed in the in vitro release study. The crushing strength and friability of the minitablets were not significantly influenced by gamma-irradiation. Based on these data, gamma-irradiation was more adequate as sterilisation method for the bioadhesive ocular minitablets than dry heat sterilisation, because it affected the least the physical properties of the minitablets. Therefore, the gamma-sterilised minitablets were selected for an in vivo evaluation in seven volunteers. The concentration of ciprofloxacin in the tear film remained above its MIC value for the most common ocular pathogens for at least 8 h. Consequently, the gamma-irradiated minitablets containing ciprofloxacin can be considered as a promising formulation to treat bacterial keratitis and conjunctivitis.

摘要

本研究的目的是评估γ射线辐照和干热灭菌对含环丙沙星的生物粘附性粉末混合物及其相应眼用微型片性质的影响。研究了用作生物粘附性制剂主要成分的滚筒干燥糯玉米淀粉（DDWM）的分子量特征、自由基的衰减动力学、生物粘附性聚合物的流变学性质以及环丙沙星的微生物活性。通过测量眼用微型片的抗压强度、脆碎度以及环丙沙星从微型片中的体外释放情况，研究了不同灭菌方法对眼用微型片特性的影响。最后，在七名健康志愿者中评估了所选灭菌微型片的临床价值。两种灭菌方法均通过诱导稳定自由基和降低DDWM的分子量，同样地影响了生物粘附性制剂的性质，尽管未检测到环丙沙星微生物活性的变化。在体外释放研究中观察到两种灭菌方法均有明显影响。γ射线辐照对微型片的抗压强度和脆碎度没有显著影响。基于这些数据，γ射线辐照作为生物粘附性眼用微型片的灭菌方法比干热灭菌更合适，因为它对微型片物理性质的影响最小。因此，选择γ射线灭菌的微型片在七名志愿者中进行体内评估。泪膜中环丙沙星的浓度在至少8小时内保持高于最常见眼部病原体的最低抑菌浓度值。因此，含环丙沙星的γ射线辐照微型片可被视为治疗细菌性角膜炎和结膜炎的一种有前景的制剂。