| Summary: | The objective of the present study was to examine the relationship between different concentrations of the chiral enhancer D-Limonene (D-LM) on the solubility of individual enantiomers and racemate Timolol maleate (TM).
The preferential improvement of D-LM on S-TM, R-TM, and racemate transported across the hairless mice skin was also investigated. For solubility studies, excess of R-, S-, or racemate with different concentrations of D-LM
were prepared. The samples were agitated, centrifuged, filtered and analyzed using HPLC with a chiral column at a wavelength of 294 nm. For skin transport studies, formulations containing 0.5% solutions of S-TM, R-TM,
or racemate in a buffer solution with predetermined concentrations of D-LM were studied. Samples of 1 ml were withdrawn and quantitatively analyzed for their TM contents. Steady-state fluxes (Jss), permeability coefficients
and the enhancement factor were calculated. The studies showed that D-LM significantly increased the solubility of the enantiomeric, as well as, the racemate forms of TM in a concentration dependent manner. The permeation
studies showed that the presence of D-LM significantly increased the flux values of both enantiomers and racemate. However, D-LM preferentially increased the permeability characteristics of the S-isomer compared to
those of the R-isomer. Solubilities of the enantiomeric and the racemate forms of TM were found to be a singlevalued function of D-LM concentration. Moreover, the addition of D-LM increased the transport of the S-TM,
R-TM enantiomers and the racemate across the hairless mice skin. In conclusion, all the tested formulations, the overall permeability characteristics of the therapeutically active TM (i.e., S-TM) proved to be superior to those obtained with the R-TM either as enantiomer or racemate.
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