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

Artif Cells Nanomed Biotechnol. 2018 Feb;46(1):138-146. doi: 10.1080/21691401.2017.1301459. Epub 2017 Mar 21.

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.

Keywords: Poly-3-hydroxybutyrate; anti-nociceptive; haemocompatibility; mechanical allodynia; poly-(ɛ-caprolactone); post-operative pain model; sustained release microspheres; thermal hyperalgesia.

MeSH terms

  • Analgesics / chemical synthesis
  • Analgesics / chemistry
  • Analgesics / pharmacology
  • Analgesics / therapeutic use
  • Animals
  • Behavior, Animal / drug effects
  • Chemical Phenomena*
  • Chemistry Techniques, Synthetic
  • Drug Carriers / chemistry*
  • Drug Liberation
  • Hemolysis / drug effects
  • Humans
  • Hydroxybutyrates / chemistry
  • Hyperalgesia / drug therapy
  • Materials Testing
  • Microspheres*
  • Nefopam / chemical synthesis
  • Nefopam / chemistry*
  • Nefopam / pharmacology*
  • Nefopam / therapeutic use
  • Pain, Postoperative / drug therapy*
  • Polyesters / chemistry
  • Rats

Substances

  • Analgesics
  • Drug Carriers
  • Hydroxybutyrates
  • Polyesters
  • polycaprolactone
  • poly-beta-hydroxybutyrate
  • Nefopam