B. Cappello et al., Solubilization of tropicamide by hydroxypropyl-beta-cyclodextrin and water-soluble polymers: in vitro/in vivo studies, INT J PHARM, 213(1-2), 2001, pp. 75-81
1% (w/v) aqueous solutions of tropicamide (TR), a poorly water-soluble mydr
iatic-cycloplegic drug, are usually obtained by adjusting the pH to similar
to 5.0, at the expense, however, of ocular tolerance and bioavailability.
The capacity of hydroxypropyl-beta -cyclodextrin (HP-beta -CD) to solubiliz
e TR in pH 7.4 0.02 M phosphate buffer was investigated in the absence and
presence of hydrophilic polymers (PVP, CMC and HPMC). Approximately 3.5% (w
/v) HP-beta -CD was required to solubilize 1% (w/v) TR in pH 7.4 buffer at
room temperature. The required amount was reduced to 0.9% (w/v) by heating
at 120 degreesC in the presence of 0.1% (w/v) HPMC. Mydriatic activity test
s in rabbits showed an improved bioavailability and maximal mydriatic respo
nse for two CD formulations, with and without HPMC, when compared to standa
rd 1% (w/v) TR eyedrops, buffered at pH 5.0. The improved in vivo behaviour
of the CD formulations are likely due to their physiological pH, resulting
in a reduced irritant effect, although an effect of HP-beta -CD on corneal
permeability cannot be dismissed a priori. (C) 2001 Elsevier Science B.V.
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