Design and evaluation of prednisolone acetate eye drops with prolonged effect

ABSTRACT

The potentiality of interaction of prednisolone acetate with six cyclodextrins [CyDs], namely alph-, beta-, gamma-, dimethyl-beta-CyD [DM-beta-CyD], trimethyl-beta-CyD [TM-beta-CyD] and hydroxypropyl-beta-cyclodextrin [HP-beta-CyD] was monitored by spectrophotometric measurements. The results revealed formation of equimolar complexes in these systems. The apparent solubility of prednisolone acetate in water was found to increase linearly with increasing CyD concentration or CyD combined with 0.25% polyvinylpyrrolidone [PVP] or hydroxyethylcellulose [HEC]. The partition coefficient of prednisolone acetate and its complexes between n-octanol and phosphate buffer of pH 6.7 was determined. The effect of CyDs on the permeation of prednisolone acetate through semi-permeable membrane was also investigated. The results revealed that all investigated CyDs increase the permeation of prednisolone acetate. The effect of CyDs or CyDs combined with 0.25% PVP or HEC on the bioavailability of prednisolone acetate eye drops was assessed by measuring the intraocular pressure [IOP] in rabbits. The results indicated the possibility of utilizing a formula containing beta-CyD together with 0.25% PVP or HEC for preparing prednisolone acetate eye drops characterized by an increased biological availability of the drug as well as a marked prolongation of its effect extending up to a period of 18 hr