Doxycycline and hydroxypropyl-β-cyclodextrin complex in poloxamer thermal sensitive hydrogel for ophthalmic delivery

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-β-cyclodextrin (HP-β-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-β-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 °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-β-CD markedly improved its stability in aqueous solution both at 8 and 40 °C. This formulation of a doxycycline-HP-β-CD inclusion complex in an in situ thermally sensitive poloxamer hydrogel represents a potentially effective ophthalmic Doxy delivery system.

Graphical abstractA chemically and physically stable formulation of doxycycline (Doxy) was prepared in this study in an in situ thermally sensitive hydrogel for ophthalmic delivery.Figure optionsDownload full-size imageDownload as PowerPoint slide