Step-2: Synthesis of prodrug (2)
SCHEME 1: SYNTHESIS PROTOCOL FOR THE PREPARATIONOF PRODRUG 2
In conclusion, the synthesized prodrug had increased solubility, synergistic antiinflammatory and antiarthritic activity with lower toxicity and less ulcerogenic activity than the parent drug EC. Thus, this prodrug approach solves not only the formulation problem of EC (lower aqueous solubility, BCS class II drug) but also reduces gastric adverse effects.
Pandey, et al.: Mutual Prodrug Synthesis of Etodolac and Glucosamine
The synthesized prodrug along with EC was evaluated for analgesic, antiinflammatory, ulcerogenic, antiarthritic activity, and histopathology study. reports result of pharmacological screenings. In analgesic study, significant reduction in number of writhes were observed after treatment with EC and EC-GLU. The result indicates initially (after 2 h of administration) advantage of EC over EC-GLU but after 3 h equimolar dose of EC-GLU to EC has better analgesic activity. It may be due to stability of prodrug in gastric pH. The antiinflammatory activities after 6 h oral dosing of EC-GLU and EC shows inhibition of edema 70.1 and 81.9%. GLU has antiinflammatory property apart from antiarthritic activity, responsible for synergistic effect on percentage inhibition of edema. EC-GLU shows better antiarthritic activity with respect to EC on 21st day. Value for ulcerogenic index shows notable difference between EC-GLU and EC. The minimized ulcerogenic index of prodrug might be due to inhibition of direct contact of carboxyl group of the drug to the gastric mucosa, which is mainly responsible for the damage. It is also due to negligible hydrolysis in stomach (pH 1.2) region as well.