Solubilization of tropicamide by hydroxypropyl-beta-cyclodextrin and water-soluble polymers: in vitro/in vivo studies.
1% (w/v) aqueous solutions of tropicamide (TR), a poorly water-soluble mydriatic-cycloplegic drug, are usually obtained by adjusting the pH to approximately 5.0, at the expense, however, of ocular tolerance and bioavailability. The capacity of hydroxypropyl-beta-cyclodextrin (HP-beta-CD) to solubilize 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 degrees C in the presence of 0.1% (w/v) HPMC. Mydriatic activity tests in rabbits showed an improved bioavailability and maximal mydriatic response for two CD formulations, with and without HPMC, when compared to standard 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.
Cappello
B
B
Dipartimento di Chimica Farmaceutica e Tossicologica, Università degli Studi di Napoli Federico II, Via D. Montesano 49, 80131 Naples, Italy. cappello@unina.it
Carmignani
C
C
Iervolino
M
M
Immacolata La Rotonda
M
M
Fabrizio Saettone
M
M
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000465:Algorithms; D000818:Animals; D003505:Cyclodextrins / Q000737:chemistry*; D008297:Male; D009184:Mydriatics / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology*; D010592:Pharmaceutic Aids; D011108:Polymers; D011817:Rabbits; D012212:Rheology; D012995:Solubility; D014331:Tropicamide / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology*; D047392:beta-Cyclodextrins
D003505:Cyclodextrins; D009184:Mydriatics; D010592:Pharmaceutic Aids; D011108:Polymers; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D014331:Tropicamide