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Preclinical evaluation of dual action intranasal formulation intended for postoperative/cancer associated therapies.
- Source :
-
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences [Eur J Pharm Sci] 2015 Aug 30; Vol. 76, pp. 48-56. Date of Electronic Publication: 2015 Apr 25. - Publication Year :
- 2015
-
Abstract
- Granisetron hydrochloride is a potent antiemetic yet experiencing first pass metabolism. Ketorolac tromethamine is a potent analgesic NSAID that is known to cause gastrointestinal complications. The purpose of this study is to prepare combined in situ nasal copolymer thermal gel combining both drugs for the management of postoperative and cancer associated nausea, vomiting and pain while avoiding the problems associated with their therapy. In situ gelling nasal formulations with/without different mucoadhesive polymers were prepared and evaluated. Viscosity of different formulations was measured and correlated to in-vitro drug release. Selected formulae were evaluated for in-vivo mucociliary transit time. Based on in-vitro release pattern and mucociliary transit time, the selected formula F4 was evaluated for chemical and thermal anti-nociception activity in rats following intranasal or intraperitoneal administration. Only the intra-nasal administration of the selected formulation F4 showed significant analgesia against chemical nociception during both the early and late phases. Also, intranasal administration of the selected formulation F4 showed significant analgesia against thermal nociception. F4 intranasal formulation may offer higher therapeutic value than oral administration as it may not only avoid granisetron first pass metabolism but may also minimize ketorolac gastrointestinal adverse effects as well.<br /> (Copyright © 2015 Elsevier B.V. All rights reserved.)
- Subjects :
- Adhesiveness
Administration, Inhalation
Administration, Oral
Analgesics chemistry
Animals
Anti-Inflammatory Agents, Non-Steroidal chemistry
Antiemetics chemistry
Chemistry, Pharmaceutical
Disease Models, Animal
Drug Carriers
Excipients chemistry
Gels
Granisetron chemistry
Hydrogen-Ion Concentration
Ketorolac Tromethamine chemistry
Kinetics
Mucociliary Clearance
Nausea chemically induced
Nociception drug effects
Polymers chemistry
Solubility
Spectrophotometry, Infrared
Technology, Pharmaceutical methods
Temperature
Viscosity
Vomiting chemically induced
Analgesics administration & dosage
Anti-Inflammatory Agents, Non-Steroidal administration & dosage
Antiemetics administration & dosage
Antineoplastic Agents adverse effects
Granisetron administration & dosage
Ketorolac Tromethamine administration & dosage
Nausea prevention & control
Pain, Postoperative prevention & control
Postoperative Nausea and Vomiting prevention & control
Vomiting prevention & control
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0720
- Volume :
- 76
- Database :
- MEDLINE
- Journal :
- European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences
- Publication Type :
- Academic Journal
- Accession number :
- 25917526
- Full Text :
- https://doi.org/10.1016/j.ejps.2015.04.015