摘要
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-b-cyclodextrin(HP-b-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-b-CD inclusion complex indicated the formation of a stable 1:1 complex.Poloxamers P407(16–22%)and P188(0–5%)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℃)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-b-CD markedly improved its stability in aqueous solution both at 8 and 401C.This formulation of a doxycycline-HP-b-CD inclusion complex in an in situ thermally sensitive poloxamer hydrogel represents a potentially effective ophthalmic Doxy delivery system.
