title: Paliperidone microemulsion for nose-to-brain targeted drug delivery system: pharmacodynamic and pharmacokinetic evaluation.
abstract: OBJECTIVE
  The objective of present study was to develop and evaluate paliperidone (PALI) loaded microemulsion (PALI-ME) for intranasal delivery in the treatment of schizophrenia.
  
  
  METHODS
  The PALI-ME was formulated by the spontaneous microemulsification method and characterized for physicochemical parameters. Pharmacodynamic assessments (apomorphine-induced compulsive behavior and spontaneous motor activity) were performed using mice. All formulations were tagged with (99m)Tc (technetium). Pharmacokinetic evaluation of PALI in the brain was investigated using Swiss albino rats. Brain scintigraphy imaging was performed in rabbits.
  
  
  CONCLUSIONS
  PALI-ME was found stable with average droplet size of 20.01 ± 1.28 nm. In pharmacodynamic studies, significant (p < 0.05) deference in parameters estimated, were found between the treated and control groups. (99m)Tc-tagged PALI solution (PALI-SOL)/PALI-ME/PALI muco-adhesive ME (PALI-MME) was found to be stable and suitable for in vivo studies. Brain-to-blood ratio at all sampling points up to 8 h following intranasal administration of PALI-MME compared to intravenous PALI-ME was found to be 6-8 times higher signifying greater extent of distribution of the PALI in brain. Rabbit brain scintigraphy demonstrated higher intranasal uptake of the PALI into the brain.
  
  
  CONCLUSIONS
  This investigation demonstrates a prompt and larger extent of transport of PALI into the brain through intranasal PALI-MME, which may prove beneficial for treatment of schizophrenia.
authors.affiliation: a Department of Pharmaceutics & Pharmaceutical Technology , Indukaka Ipcowala College of Pharmacy , New Vallabh Vidyanagar , Gujarat , India .
authors.forename: Mrunali R
authors.initials: MR
authors.lastname: Patel
authors.affiliation: b Department of Pharmceutical Chemistry & Quality Assurance , A.R. College of Pharmacy & G.H. Patel Institute of Pharmacy , Vallabh Vidynagar , Gujarat , India .
authors.forename: Rashmin B
authors.initials: RB
authors.lastname: Patel
authors.affiliation: b Department of Pharmceutical Chemistry & Quality Assurance , A.R. College of Pharmacy & G.H. Patel Institute of Pharmacy , Vallabh Vidynagar , Gujarat , India .
authors.forename: Kashyap K
authors.initials: KK
authors.lastname: Bhatt
authors.affiliation: c Department of Pharmacology & Clinical Pharmacy , Charotar University of Science and Technology , Changa , Gujarat , India , and.
authors.forename: Bharat G
authors.initials: BG
authors.lastname: Patel
authors.affiliation: d Veterinary Nuclear Medicine Center , Bombay Veterinary College , Mumbai , India.
authors.forename: Rajiv V
authors.initials: RV
authors.lastname: Gaikwad
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000494:pharmacology; D001058:Apomorphine; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D002626:Chemistry, Pharmaceutical; D003192:Compulsive Behavior / Q000139:chemically induced / Q000188:drug therapy / Q000523:psychology; D016503:Drug Delivery Systems; D004655:Emulsions; D005260:Female; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009297:Nasal Mucosa / Q000378:metabolism; D000068882:Paliperidone Palmitate / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000494:pharmacology; D011817:Rabbits; D011877:Radionuclide Imaging; D051381:Rats; D017208:Rats, Wistar; D013667:Technetium / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D014150:Antipsychotic Agents; D004655:Emulsions; D013667:Technetium; D001058:Apomorphine; D000068882:Paliperidone Palmitate
keywords: Brain scintigraphy; microemulsion; paliperidone; pharmacodynamic study; pharmacokinetic study