Preclinical evaluation of dual action intranasal formulation intended for postoperative/cancer associated therapies.
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.
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Egypt. Electronic address: doaaahmed@hotmail.com.
Doaa Ahmed
DA
El-Setouhy
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Egypt.
Sami
S
Ahmed
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Egypt.
Alia Abd El-Latif
AA
Badawi
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Egypt.
Mohamed Ahmed
MA
El-Nabarawi
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Egypt.
Nada
N
Sallam
D000268:Adhesiveness; D000280:Administration, Inhalation; D000284:Administration, Oral; D000700:Analgesics / Q000008:administration & dosage* / Q000737:chemistry; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000737:chemistry; D000932:Antiemetics / Q000008:administration & dosage* / Q000737:chemistry; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002626:Chemistry, Pharmaceutical; D004195:Disease Models, Animal; D004337:Drug Carriers; D005079:Excipients / Q000737:chemistry; D005782:Gels; D017829:Granisetron / Q000008:administration & dosage* / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D020911:Ketorolac Tromethamine / Q000008:administration & dosage* / Q000737:chemistry; D007700:Kinetics; D009079:Mucociliary Clearance; D009325:Nausea / Q000139:chemically induced / Q000517:prevention & control*; D059225:Nociception / Q000187:drug effects; D010149:Postoperative Pain / Q000517:prevention & control*; D011108:Polymers / Q000737:chemistry; D020250:Postoperative Nausea and Vomiting / Q000517:prevention & control*; D012995:Solubility; D013055:Spectrophotometry, Infrared; D013678:Technology, Pharmaceutical / Q000379:methods; D013696:Temperature; D014783:Viscosity; D014839:Vomiting / Q000139:chemically induced / Q000517:prevention & control*
D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000932:Antiemetics; D000970:Antineoplastic Agents; D004337:Drug Carriers; D005079:Excipients; D005782:Gels; D017829:Granisetron; D020911:Ketorolac Tromethamine; D011108:Polymers
Granisetron; Ketorolac; Mucosal drug delivery; Nasal drug delivery; Thermal gels