Nefopam hydrochloride loaded microspheres for post-operative pain management: synthesis, physicochemical characterization and in-vivo evaluation

Abstract

Once-daily oral dosage of nefopam hydrochloride loaded sustained release microspheres (NPH-MS) was investigated as novel therapeutic strategy for post-operative pain management. Microspheres were synthesized using poly-3-hydroxybutyrate and poly-(ɛ-caprolactone) by double emulsion solvent evaporation technique. NPH-MS were characterized through FTIR, PXRD and SEM. In-vitro drug release study revealed sustained behavior till 24 h. Haemolysis was <5% which signified haemocompatibility of formulation. ED50 in rat tail-flick anti-nociceptive test was found ∼18.12 mg/kg. In post-operative pain model, reversal of mechanical allodynia and thermal hyperalgesia by NPH-MS was statistically significant (p < .001) as compared with NPH till 24 h post-dose.

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“…X i represents average outcome of changing one variable at a time from low to high, polynomial terms X i 2 was employed to assess non-linearity effect of variable X i , interaction terms X i X j illustrated how the response transforms when two variables X i and X j were altered concurrently. Production Methodology: Double emulsion solvent evaporation method was employed for manufacturing NPH-MS 7 . NPH dispersed in distilled water: acetone (1:1) was extruded gradually through syringe #20 to solution of PHB, PCL and sorbitan monooleate (0.5% w/v) in dichloromethan.…”

“…In this research, nefopam hydrochloride loaded microspheres (NPH-MS) were synthesized employing mixture of poly-3-hydroxybutyrate (PHB) and poly-ε-caprolactone (PCL) by double emulsion solvent evaporation method 7 . Central composite quality-by-design (QbD) approach has been applied for optimizing critical formulation / process variables with least number of experiments.…”