Biodegradable ocular inserts for sustained delivery of brimonidime tartrate: preparation and in vitro/ in vivo evaluation

ABSTRACT

As the bioavailability of therapeutic agents from eye drops is usually limited due to corneal barrier functions and effective eye protective mechanisms, the current study aims to enhance ocular bioavailability of brimonidine, a potent antiglucoma drug, through the preparation of ocular inserts. Solvent casting technique was employed to prepare the inserts using polyvinylpyrrolidone K90 [PVP K-90] as film forming polymer blended with different viscosity grades of bioadhesive polymers, namely hydroxypropylmethycellulose, carbopol, sodium alginate and chitosan. The ocular inserts prepared were evaluated for various physicochemical parameters, swelling behavior and in vitro release patterns. Sodium alginate based ocular inserts revealed the most sustainment in drug release [99% at 6 hr], so it was selected for further modifications via coating it, on one side or dual sides, using hydrophobic film composed of either ethylcellulose or Eudragit RSPO. The in vitro release results obtained for the modified ocular inserts revealed that ethylcellulose is superior to Eudragit RSPO in terms of brimonidine release sustainment effect. Ocular inserts composed of 7% PVP-K 90, 1.5% low molecular weight sodium alginate with or without ethylcellulose coat were able to sustain the in vitro release of brimonidine. Their therapeutic efficacy regarding intraocular pressure [IOP] lowering effect when inserted in albino rabbits' eyes showed superior sustainment effect compared to that of brimonidine solution. Furthermore, due to both the mucoadhesive property and the drug sustainment effect, the one side coated ocular insert showed more IOP lowering effect compared to the non-coated or dual side coated counterpart