Formulation of intranasal mucoadhesive temperature-mediated in situ gel containing ropinirole and evaluation of brain targeting efficiency in rats

Abstract

Mucoadhesive temperature-mediated in situ gel formulations using chitosan and hydroxyl propyl methyl cellulose were used to enhance intranasal (i.n.) delivery of the dopamine D2 agonist ropinirole to the brain. Formulations were tested for gelation time, thermosensitivity, mucoadhesion, in vitro release and permeation, in vitro cytotoxicity, nasal clearance, in vivo bioavailability and brain uptake. In vivo bioavailability and brain uptake of ropinirole were assessed in albino rats following intranasal administration of 99mTc-ropinirole in situ gel, intranasal ropinirole solution and intravenous (i.v.) ropinirole solution. Radiolabeled ropinirole uptake was calculated as a fraction of administered dose. The absolute bioavailabilty of ropinirole from the temperature-mediated in situ gelling nasal formulation was 82%. The AUC 0–480 min in brain after nasal administration of ropinirole in situ gel was 8.5 times (869 ± 250% · min/g versus 102 ± 20% · min/g) that obtained following i.v. administration, this value was also considerably higher (869 ± 250% · min/g versus 281 ± 52% · min/g) than that achieved with intranasal ropinirole solution. High brain direct drug transport percentage (DTP; 90.36%) and drug targeting index (DTI) > 1 confirms direct nose to brain transport of the intranasal in situ gel formulation of ropinirole.