DICLOFENAC

Pain is a multifaceted phenomenon that encompasses both sensory and emotional elements and is often linked with anxiety. This research investigated the effects of diclofenac, orphenadrine, and their combination on pain perception and anxietyrelated behaviours in mice. Twenty-four albino mice weighing 22–32 g were randomly a signed to four groups and administered saline (10 mL/kg, control), diclofenac (50 mg/kg, intraperitoneally), orphenadrine (25 mg/kg, orally), and orphenadrine (25mg/kg) + diclofenac (50mg/kg). Anxiety-like behaviour was evaluated using the Hole Board Apparatus, while analgesic activity was measured using the Formalin-Induced Paw-Licking Test. In silico studies were also carried out to test for serotonergic activity of the drugs. In the formalin test, diclofenac significantly decreased paw-licking time in both the early and late phases (*p < 0.05), demonstrating strong peripheral analgesic activity. Orphenadrine showed a moderate reduction in nociceptive behaviour, while the combined treatment produced the greatest analgesic effect (***p < 0.001 vs. control, #p < 0.05 vs. orphenadrine), indicating a possible synergistic interaction between the two agents

Background: Self emulsifying drug delivery systems (SEDDS) offer a means of enhancing the bioavailability and therapeutic efficacy of drugs with poor water solubility. The aim of this study is to formulate and evaluate a self emulsifying drug delivery system of diclofenac potassium using palm oil as the lipid phase.
Method: Five batches of SEDDS labelled B1, B2, B3, B4, B5 were prepared by incorporating diclofenac potassium in SEDDS bases of palm oil and Tween 80 at varying component ratios. The resulting formulations were evaluated for their self-emulsification performance upon dilution with water by visual inspection and classified according to standard emulsion grading criteria (Grade A, B, or C). They were evaluated for their stability and Absorbance values.
Result: The emulsification performance demonstrated significant variability across the batches, with Batch B1 successfully forming a highly stable Grade A emulsion, indicating rapid and fine self-microemulsification. Conversely, Batches B2 and B3 yielded a satisfactory Grade B emulsion, whereas Batches B4 and B5 resulted in a milky Grade C emulsion, signifying poor emulsification performance. Batches B1, B2 and B3 showed stability,while batches B4 and B5 showed poor stability. The batches had absorbance values which ranged from 0.579 ±0.006 to 0.713 ±0.004 showing considerable drug entrapment.
Conclusion: The optimal performance of Batch B1 confirms that diclofenac potassium can be successfully formulated into a stable SEDDS using palm oil, providing a practical, scalable, and effective strategy for enhanced in vitro dissolution and potential clinical application.

Background: Acute pain is a complex experience involving both sensory perception and significant affective components, particularly anxiety. This interaction is mediated by shared neural pathways and potentially linked to oxidative stress. This study investigates the comparative anxiotropic effects of orphenadrine and diclofenac, alone and in combination, focusing on their ability to modulate anxiety-like behaviour and associated oxidative damage in acute pain in mice. Methods: Twenty-four mice were allocated into four groups receiving normal saline (10ml/kg), orphenadrine (25mg/kg), diclofenac (50mg/kg), and an orphenadrine–diclofenac combination at the aforementioned doses. Peripheral analgesia was assessed with the acetic-acid–induced writhing assay while anxiety-like behavior was evaluated the following day, using the elevated plus maze. Animals were euthanized, brain tissue was excised and fixed in 10% formalin, and brain MDA was quantified by TBA derivatization and HPLC.
Results: Diclofenac and the orphenadrine-diclofenac combination demonstrated superior analgesic activity (p < 0.01 to p < 0.001). Both orphenadrine (p < 0.0001) and diclofenac (p < 0.001) were associated with significantly elevated MDA levels compared to the control group, while the combination group showed a reduction in MDA compared to either drug alone. All three treatment groups saw a decrease in the time spent in the open arm and a modest increase in time spent in the closed arms of the EPM, compared to the control group (p < 0.001). All drugs were associated with a decrease in the number of entries into the open arm, while orphenadrine uniquely led a significant reduction in closed arm entries (p < 0.01) compared to the control, an effect not seen with diclofenac or the combination groups.
Conclusion: Data from this study shows that all three analgesic treatments were associated with significantly increased anxiety-like behavior and accompanying oxidative damage.