Development and optimization of nasal delivery of ketorolac
Various nasal formulations have been tested for their suitability to deliver drug through nasal cavity. This route is especially of interest where dose of drug is small and the drug may undergo an extensive first-pass metabolism and/or decomposition while passing through the gastrointestinal tract. Unfortunately, the nasal mucosa does not have same type of tolerability to all drugs and additives used in formulations. Some chemicals may damage the nasal epithelia or alter the mucociliary defensive mechanism of the nose. Several methods have been developed to study the impact of drugs and excipients on the integrity of the nose. The first part of the thesis provided a review of toxicological evaluation of different drugs and additives used to optimize a nasal formulation. ^ The research project involves the development of a nasal formulation of ketorolac for the treatment of postoperative pain and migraine headache. Migraine treatment by administering drugs via oral route is ineffective due to the dysfunction and atony of the gastrointestinal tract as well as closure of the pyloric sphincter during attack. Thus, the nasal route may be a suitable alternate mode of delivery and may be more convenient than injection. Different spray and lyophilized powder formulations of ketorolac were administered through the nasal cavity of rabbits. Bioadhesive polymer was used to increase the residence time of the drugs in the nasal epithelium. The spray and powder formulations were compared by determining their pharmacokinetics parameters and absolute bioavailability. The area under the curve was calculated using pharmacokinetic software MK model. Drug plasma concentrations were assessed via solid phase extraction, followed by an HPLC analysis method. Nasal spray formulations were significantly more effective than powder formulations. There were no significant differences in absorption among different powder formulations. The nasal spray formulation of ketorolac tromethamine showed the highest absorption with an absolute bioavailability of 91%. The stability study indicated that this formulation was quite stable with only 4% degradation in three months at 45°C temperature. ^ An endoscopic observation of the rabbit nasal cavity was performed to assess the gross morphological changes after exposure to different time period. The release of total protein and acid phosphatase, which serves as a marker of epithelial cell damage, was measured by perfusion technique. ^
Health Sciences, Toxicology|Chemistry, Pharmaceutical|Health Sciences, Pharmacy
Muhammad Anisul Quadir,
"Development and optimization of nasal delivery of ketorolac"
Dissertations and Master's Theses (Campus Access).