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

Authors

DOI:

https://doi.org/10.15587/2519-4852.2022.253474

Keywords:

paracetamol, N-acetyl-D-glucosamine, tablet, rats, analgesics, L-α-dimyristoylphosphatidylcholine (DMPC), differential scanning calorimetry (DSC), lipid membrane

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

Author Biographies

Olena Ruban, National University of Pharmacy

Doctor of Pharmaceutical Sciences, Professor, Head of Department

Department of Industrial Technology of Drugs

Ihor Zupanets, National University of Pharmacy

Department of Industrial Technology of Drugs

Tetiana Kolisnyk, National University of Pharmacy

PhD, Assistant Professor

Department of Industrial Technology of Drugs

Sergii Shebeko, National University of Pharmacy

Doctor of Pharmaceutical Sciences, Professor

Department of Clinical Pharmacology and Clinical Pharmacy

Olga Vashchenko, State Scientific Institution “Institute for Single Crystals” of National Academy of Sciences of Ukraine

Doctor of Physical and Mathematical Sciences, Senior Scientist, Leading Researcher

Yu. V. Malyukin Department of Nanostructural Materials

Institute of Scintillation Materials

Stanislav Zimin, National University of Pharmacy

PhD, Associate Professor

Department of Clinical Pharmacology and Clinical Pharmacy

Olena Dolzhykova, National University of Pharmacy

Doctor of Pharmaceutical Sciences, Associate Professor

Department of Clinical Laboratory Diagnostics

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Published

2022-02-28

How to Cite

Ruban, O., Zupanets, I., Kolisnyk, T., Shebeko, S., Vashchenko, O., Zimin, S., & Dolzhykova, O. (2022). Pharmacological and biopharmaceutical studies of paracetamol and N-acetyl-D-glucosamine combination as an analgetic drug. ScienceRise: Pharmaceutical Science, (1(35), 28–36. https://doi.org/10.15587/2519-4852.2022.253474

Issue

No. 1(35) (2022)

Section

Pharmaceutical Science

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Copyright (c) 2022 Olena Ruban, Ihor Zupanets, Tetiana Kolisnyk, Sergii Shebeko, Olga Vashchenko, Stanislav Zimin, Olena Dolzhykova

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