title: Thermo-sensitive gels containing lorazepam microspheres for intranasal brain targeting.
abstract: Thermo-sensitive gels containing lorazepam microspheres were developed and characterized for intranasal brain targeting. Pluronics (PF-127 and PF-68) have been selected since they are thermo-reversible polymers with the property of forming a solution at low temperatures (4-5 °C), and a gel at body temperature (37 °C). This property makes them an interesting material to work with, especially in case of controlled release formulations. The present study focuses on the development of an intranasal formulation for lorazepam, as an alternative route of drug delivery to the brain. Direct transport of drugs to the brain circumventing the brain barrier, following intranasal administration, provides a unique feature and better option to target brain. The presence of mucoadhesive microspheres in the gel vehicle via nasal route can achieve a dual purpose of prolonged drug release and enhanced bioavailability. To optimise the microsphere formulation, Box Behnken design was employed by investigating the effect of three factors, polymer concentration (chitosan), emulsifier concentration (Span 80) and cross-linking agent (glutaraldehyde) on the response variable which is the mean particle size. The concentration of 21% PF-127 and 1% PF-68 were found to be promising gel vehicles. The results showed that the release rate followed a prolonged profile dispersion of the microspheres in the viscous media, in comparison to the microspheres alone. Histopathological studies proved that the optimised formulation does not produce any toxic effect on the microscopic structure of nasal mucosa.
authors.affiliation: Department of Pharmaceutical Sciences, Mahatma Gandhi University, Cheruvandoor Campus, Ettumanoor P.O., Kerala 686 631, India. sajanjose@hotmail.com
authors.forename: S
authors.initials: S
authors.lastname: Jose
authors.forename: C R
authors.initials: CR
authors.lastname: Ansa
authors.forename: T A
authors.initials: TA
authors.lastname: Cinu
authors.forename: A J
authors.initials: AJ
authors.lastname: Chacko
authors.forename: N A
authors.initials: NA
authors.lastname: Aleykutty
authors.forename: S V
authors.initials: SV
authors.lastname: Ferreira
authors.forename: E B
authors.initials: EB
authors.lastname: Souto
mesh_terms: D000268:Adhesiveness; D000281:Administration, Intranasal; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D001682:Biological Availability; D001692:Biological Transport; D001921:Brain / Q000378:metabolism*; D002417:Cattle; D048271:Chitosan / Q000737:chemistry; D003432:Cross-Linking Reagents / Q000737:chemistry; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems; D005079:Excipients / Q000737:chemistry; D005782:Gels; D005976:Glutaral / Q000737:chemistry; D006601:Hexoses / Q000737:chemistry; D008140:Lorazepam / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D008863:Microspheres; D009297:Nasal Mucosa / Q000378:metabolism; D010316:Particle Size; D020442:Poloxamer / Q000737:chemistry; D013696:Temperature
chemical_list: D000927:Anticonvulsants; D003432:Cross-Linking Reagents; D003692:Delayed-Action Preparations; D005079:Excipients; D005782:Gels; D006601:Hexoses; C018665:sorbitan monooleate; D020442:Poloxamer; D048271:Chitosan; D008140:Lorazepam; D005976:Glutaral