期刊
ACTA PHARMACEUTICA SINICA B
卷 1, 期 4, 页码 254-260出版社
INST MATERIA MEDICA, CHINESE ACAD MEDICAL SCIENCES
DOI: 10.1016/j.apsb.2011.10.004
关键词
Doxycycline; HP-beta-CD; Corneal neovascularization; Thermally sensitive; Hydrogel
The present study aimed to prepare a chemically and physically stable formulation of doxycycline (Doxy) in an in situ thermally sensitive hydrogel for ophthalmic delivery. An inclusion complex of Doxy and hydroxypropyl-beta-cyclodextrin (HP-beta-CD) was first developed to increase the stability of Doxy in aqueous solution. The physical characteristics (phase solubility profiles, thermal analysis, X-ray powder diffractograms and infrared spectra) of the Doxy-HP-beta-CD inclusion complex indicated the formation of a stable 1:1 complex. Poloxamers P407 (16-22 A) and P188 (0-5 A) were mixed to obtain a hydrogel with an appropriate gelation temperature for opthalmic use. Formulation of the inclusion complex in the poloxamer hydrogel exhibited a suitable gelation temperature (33.3 degrees C) after dilution with simulated tear fluid (Gel:STF = 40:7, v/v). The release of Doxy from the poloxamer hydrogel followed a zero order equation suggesting it occurs through corrosion of the poloxamer hydrogel. Stability studies demonstrated that the inclusion of Doxy by HP-beta-CD markedly improved its stability in aqueous solution both at 8 and 40 degrees C. This formulation of a doxycycline-HP-beta-CD inclusion complex in an in situ thermally sensitive poloxamer hydrogel represents a potentially effective ophthalmic Doxy delivery system. (C) 2011 Institute of Materia Medica, Chinese Academy of Medical Sciences and Chinese Pharmaceutical Association. Production and hosting by Elsevier B.V. All rights reserved.
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