Pharmacological and biopharmaceutical studies of paracetamol and N-acetyl-D-glucosamine combination as an analgetic drug

Abstract

The aim. Experimental selection of paracetamol and N-acetyl-D-glucosamine (NAG) ratio and combined dose and bioavailability study of the pharmaceutical composition and active pharmaceutical ingredient (API) in the model of cell biomembranes.
 Materials and methods. The following substances were used: paracetamol, Actimask Acetaminophen (gelatin-coated paracetamol), and NAG. For pharmacological studies were used laboratory rats, which received test objects intragastrically. The study was performed on the model of inflammatory hyperalgesia according to the Randall-Selitto method. The values of pain threshold before and after pathology induction were established. For biopharmaceutical studies, dry L-α-dimyristoylphosphatidylcholine purchased from Avanti Polar Lipids (purity 99.9 %) was used, hydrated with an appropriate amount of double-distilled water to obtain 70 % wt./wt. water dispersion. Differential scanning calorimetry (DSC) studies were performed employing DSC 1 microcalorimeter (Mettler Toledo). Pharmaceuticals investigated were placed on the bottom of a crucible, then a proper amount of the lipid membrane was added and this moment was taken as the time reference point (t=0). Then a crucible was sealed with a lid and a sample was undergone consecutive temperature scans, heating from 0 to 35 ºC at a scanning rate of 2 ºC/min. The procedure was repeated until no more changes in DSC profiles were observed, i.e. system equilibrium was reached.
 Results. It has been experimentally proven that the combination of paracetamol and NAG in the ratio of 4:1 showed better analgesic efficacy. The dose of active ingredients was determined to be 50 mg/kg by the sum of API. The active interaction of paracetamol with the bilayer of biomembranes was established and it was determined that Actimask has a worse rate of penetration into the membrane due to the coating of paracetamol with a gelatin shell. NAG didn't significantly affect the rate of penetration of Actimask through the bilayer of membranes, but the auxiliary components of the tablet mixture significantly improved the rate and completeness of penetration of paracetamol through the bilayer of biomembranes.
 Conclusions. The study found the most effective ratio between paracetamol and NAG in the composition, which is 4:1. The next step was to determine the dose of API, which is 50 mg/kg of the sum of active substances. It has been determined that paracetamol has good permeability through the bilayer of biomembranes, and the tablet mass significantly improves the permeability of paracetamol

Kinetic biopharmaceutical studies of a new paracetamol–glucosamine analgetic drug

“…To our mind, such effect could be resulted from both enhancement of paracetamol distribution into membrane and its overlapping with membranotropic effect of other drug components. But anyway, such membrane fluidization correlates well with the previously established enhancement of analgetic effect of the drug [1]. Analysis of T(t) dependences (Fig.…”

“…Several types of systems were investigated, viz., DMPC membrane containing a selected drug component (paracetamol, NAG), certain drug combinations (e.g., Actimask® + NAG) or the full drug formulation (tablet). Original DSC thermograms of the systems were reported in [1]. Here, we present further data treatment allowing us to obtain quantitative characteristics of drug-membrane interactions.…”

“…To avoid it, N-acetyl-D-glucosamine (NAG) was used in a drug formulation as a hepatoprotector. It was established that the paracetamol-NAG combination leads to increased safety and potentiation of the analgesic effect of the drug [1]. Microgranules of paracetamol in a gelatin shell (Actimask® Acetaminoprofen) was used in order to create the drug in the form of orally disintegrating tablet, which provides greater compliance for treatment and contributes to the onset of an analgesic effect; besides, covering paracetamol with a gelatin shell is due to the improvement of its organoleptic properties.…”