A Novel Approach for the Availability and Ocular Delivery of Tenoxicam Potassium: Synthesis, Characterization, and In Vivo Application

• Published in: AAPS PharmSciTech Vol. 24; no. 1; p. 44
• Main Authors: Osman, Shaaban K., Yassin, Taher M., Mohammed, Ahmed M., Alfayomy, Abdallah M., Abdellatif, Ahmed A., Mahdi, Wael A., Alshehri, Sultan, Hamd, Mohamed A. El, Sarhan, Hatem, Ibrahim, Mohammed A.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 26-01-2023
• Subjects: Animals; Anti-Inflammatory Agents, Non-Steroidal; Biochemistry; Biomedical and Life Sciences; Biomedicine; Biotechnology; Drug Delivery Systems - methods; Male; Ophthalmic Solutions; Pharmacology/Toxicology; Pharmacy; Piroxicam; Rabbits; Research Article; tenoxicam potassium salt; carrageenan-induced inflammation; release; viscosity-imparting agents; in vitro release
• ISSN: 1530-9932; 1530-9932
• DOI: 10.1208/s12249-022-02487-3

Tenoxicam (TX) is a non-steroidal anti-inflammatory agent that can be used to control pain in various ophthalmic lesions like cataracts, refractive surgery, and corneal abrasion. TX has a very slightly aqueous solubility of 0.072 mg/mL resulting in difficulty to be formulated in ophthalmic solutions. This study aims to improve TX solubility by converting it into its potassium salt to achieve a target of 10 mg/mL (1%w/v) concentration of TX in the desired aqueous medium for the formulation of aqueous ophthalmic solutions. The synthesized TX salt was characterized by different evaluation parameters such as solubility studies,
1
H NMR, IR, and elemental analyses. Different TX potassium solutions were formulated at concentrations of 0.5% and 1% w/v using different viscosity-imparting agents. The prepared solutions were characterized for their physicochemical properties including visual inspection, pH, rheological,
in vitro
release, and kinetic behavior. Also, the formulations were biologically evaluated
in vivo
using male albino rabbits. The obtained results showed the successful synthesis of TX salt, as indicated by IR and NMR, and elemental analysis. The solubility study showed that the solubility of TX was improved hugely to 18 mg/mL (250-fold). In addition, the results showed that the prepared formulations showed acceptable physicochemical properties. The highest release rate was obtained with formula F1, which contains no viscosity-imparting agents. While as, the lowest release rate was obtained in the case of formula F9, composed of Pluronic F127 (12% w/v). The
in vivo
results showed that TX optimized ophthalmic solutions F8 and F9 inhibited the redness and edema in an extended or sustained manner.