Comparative Bioavailability Study of a New Formulation of Injection of 75 mg Diclofenac Sodium in 1 mL with the Conventional Injection of 75 mg Diclofenac Sodium Given in 3 mL Volume

Dhaneshwar      Shep; Ashwini      Ojha; Sweta      Patel; Manish      Nivsarkar; Vijaya      Jaiswal; Harish      Padh

Abstract

Objectives: Diclofenac a non-steroidal anti-inflammatory drug (NSAID) is widely used for the management of various musculoskeletal conditions. An injectable test formulation of diclofenac sodium (75 mg/mL) was prepared to facilitate reduction in injection volume as compared to already marketed formulations of diclofenac sodium (75 mg/3mL). The objective of this study was to compare the bioavailability of test formulation with the reference formulation given intramuscularly in healthy volunteers.

Methods: This two way randomized crossover study was performed in 14 healthy, adult, Indian, male human subjects to compare bioavailability. The formulations were administered intramuscularly (intragluteal) to the volunteers in a two way randomized fashion with a wash out period of 6 days. Blood samples were collected till 6.0 h following drug administration. The samples were analyzed using pre-validated HPLC method.

Results: The mean C_max and T_max for the test and reference formulations were 2.14 μg/mL, 1.91 μg/mL and 0.49 h, 0.50 h respectively. The mean AUC_0-t for test and reference formulations were 3.79 μg.h/mL, and 3.43 μg.h/mL respectively. The mean AUC_0-∞ for test and reference formulation were 4.03 μg.h/mL and 3.65 μg.h/mL respectively. The mean (90% CI) C_max, AUC_0-t and AUC_0-∞ ratio (Test:Reference) were 1.15 (100.25 – 132.99), 1.10 (100.34 – 119.96) and 1.09 (100.78 – 118.88), respectively.

Conclusion: The test formulation shows a comparable AUC_0-t and AUC_0-∞ but a higher C_max in comparison to the reference when given intra-gluteally. The lower volume of the test formulation offers advantage of injection at other sites, like deltoid region. Absence of propylene glycol in the test formulation could be advantageous in terms of improved tolerability. Hence, such formulations of previously well established molecules provide a new direction towards developing better and convenient dosing alternatives.

Keywords: Bioavailability, diclofenac sodium, intragluteal, injection, pharmacokinetics, volume, leukocytes, Parameters, dichloromethaness, anti-inflammatory drug