title: Nasal in-situ gels for delivery of rasagiline mesylate: improvement in bioavailability and brain localization.
abstract: Intranasal thermosensitive gel for rasagiline mesylate (RM) was developed for effective treatment of Parkinson's disease. Intranasal gels were prepared by combination of poloxamer 407 and poloxamer 188 (1:1) with mucoadhesive polymers (carbopol 934 P and chitosan). The formulations were evaluated for sol-gel transition temperature, in-vitro drug release and in-vivo mucociliary transit time. Further, optimal intranasal gel formulations were tested for in-vivo pharmacokinetic behavior, nasal toxicity studies and brain uptake studies. It was found that optimal formulations had acceptable gelation temperature (28-33 °C) and adequate in-vitro drug release profile. Pharmacokinetic study in rabbits showed significant (p < 0.05) improvement in bioavailability (four- to six-folds) of the drug from intranasal gels than oral solution. Chronic exposure studies in Wistar rats showed that these intranasal gels were non-irritant and non-toxic to rat nasal mucosa. Estimation of RM in rat brain tissue showed significant (p < 0.01) improvement in uptake of RM form intranasal gel formulations than nasal solution.
authors.affiliation: a Pharmacy Department , BITS-Pilani Hyderabad Campus , Jawaharnagar , Andhra Pradesh , India.
authors.forename: P R
authors.initials: PR
authors.lastname: Ravi
authors.affiliation: a Pharmacy Department , BITS-Pilani Hyderabad Campus , Jawaharnagar , Andhra Pradesh , India.
authors.forename: N
authors.initials: N
authors.lastname: Aditya
authors.affiliation: a Pharmacy Department , BITS-Pilani Hyderabad Campus , Jawaharnagar , Andhra Pradesh , India.
authors.forename: S
authors.initials: S
authors.lastname: Patil
authors.affiliation: a Pharmacy Department , BITS-Pilani Hyderabad Campus , Jawaharnagar , Andhra Pradesh , India.
authors.forename: L
authors.initials: L
authors.lastname: Cherian
mesh_terms: D000179:Acrylates / Q000737:chemistry; D000281:Administration, Intranasal; D000818:Animals; D001682:Biological Availability; D001921:Brain / Q000378:metabolism*; D048271:Chitosan / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D065546:Drug Liberation; D005260:Female; D005782:Gels; D007189:Indans / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity; D020442:Poloxamer / Q000737:chemistry; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D013696:Temperature; D014018:Tissue Distribution; D044366:Transition Temperature
chemical_list: D000179:Acrylates; D004337:Drug Carriers; D005782:Gels; D007189:Indans; D018696:Neuroprotective Agents; C031967:rasagiline; D020442:Poloxamer; D048271:Chitosan; C453622:carbopol 934P
keywords: Bioavailability; brain distribution; intranasal gels; pharmacokinetic studies; rasagiline mesylate