Examination of the physical state of chlorhexidine within viscoelastic, bioadhesive semisolids using Raman spectroscopy

This study examined the effects of polymeric components on the physical sta te of chlorhexidine within bioadhesive, semisolid formulations using Raman spectroscopy. Semisolid formulations were prepared in which chlorhexidine b ase (CHX, 5%w/w, particle size <63 mu m) was dispersed in aqueous (phosphat e-buffered saline, pH 6.8) polymer matrices consisting of one or more polym eric components, namely HEC (3%w/w), PVP (3%), and PC (PC, 3%). Raman spect ra were recorded using 785-nm excitation and were typically accumulated for 360 s. The Raman spectra were dominated by the presence of CHX. The spectr a of CHX in HEC and in HEC/PVP gels were indistinguishable from that for so lid CHX as a result of the insolubility of CHX in these formulations. Howev er, in systems containing PC and CHX, there was a shift in the strongest ba nd from 1564 cm(-1) to 1608 cm(-1), which may be accredited to protonation of the basic CHX by the numerous carboxylic acidic groups on PC. Identical shifts in the band positions were observed when this protonation was modele d using ethanoic acid, supporting the view that there was a simple acid bas e reaction between PC and CHX. However, there were notable differences in t he relative intensities of the peaks from these samples, with the spectrum of CHX in the PC matrix displaying properties intermediate between those of CHX dissolved in ethanoic acid and solid CHX diacetate. This may be accred ited to the limited solubility of the CHX-PC ion pair. In matrices containi ng HEC and PC, no peak was observed at 1564 cm-l, whereas the intensity of the peak at 1608 cm(-1) was increased. Therefore, in these formulations CHX was completely converted to the di-cation as a result of the synergistic e ffects of PC (which protonated CHX) and HEC (which solubilized the di-catio n). In the absence of either HEC or PC, complete protonation was not achiev ed. It is suggested that this enhancement of solubility of H2CHX2+ may be d ue to hydrogen bonding, given the hydroxylated nature of HEC. In conclusion , this study has shown the applicability of Raman spectroscopy for both the analysis of opaque, semisolid formulations and, additionally, for the exam ination of the state of therapeutic agents within such matrices. In particu lar, using Raman spectroscopy, it was uniquely possible to identify the rol es of various polymeric components on both the ionization and solubilizatio n of CHX within aqueous semisolid systems. Copyright (C) 2000 Wiley Liss, I nc.