A randomized single-dose, two-period crossover bioequivalence study of two fixed-dose Paracetamol/Orphenadrine combination preparations in healthy volunteers under fasted condition

Abstract

Background: Paracetamol/Orphenadrine is a fixed dose combination containing 35 mg orphenadrine and 450 mg paracetamol. It has analgesic and muscle relaxant properties and is widely available as generics. This study is conducted to investigate the relative bioavailability and bioequivalence between one fixed dose paracetamol/ orphenadrine combination test preparation and one fixed dose paracetamol/orphenadrine combination reference preparation in healthy volunteers under fasted condition for marketing authorization in Malaysia. Method: This is a single-center, single-dose, open-label, randomized, 2-treatment, 2-sequence and 2-period crossover study with a washout period of 7 days. Paracetamol/Orphenadrine tablets were administered after a 10-h fast. Blood samples for pharmacokinetic analysis were collected at scheduled time intervals prior to and up to 72 h after dosing. Blood samples were centrifuged, and separated plasma were kept frozen (− 15°C to − 25°C) until analysis. Plasma concentrations of orphenadrine and paracetamol were quantified using liquid-chromatographytandem mass spectrometer using diphenhydramine as internal standard. The pharmacokinetic parameters AUC 0-∞ , AUC 0-t and C max were determined using plasma concentration time profile for both preparations. Bioequivalence was assessed according to the ASEAN guideline acceptance criteria for bioequivalence which is the 90% confidence intervals of AUC 0-∞ , AUC 0-t and C max ratio must be within the range of 80.00-125.00%.

Utilizing experimental design and desirability function in optimizing RP-HPLC method for simultaneous determination of some skeletal muscle relaxants and analgesics

“…Methocarbamol (MTL) is a centrally acting muscle relaxant with the chemical name ( ±)-3-( o -methoxyphenoxy)-1,2-propanediol-1-carbamate 7 , which is commonly used for the short-term symptomatic treatment of muscle spasms and is also used in combination with non-steroidal anti-inflammatory drugs such as ibuprofen to treat musculoskeletal disorders such as painful muscle spasms 8 . Orphenadrine citrate (ORF), chemically known as ( ±)-N,N-Dimethyl-2-[( o -methyl-α phenylbenzyl)oxyethylamine citrate, is a centrally acting skeletal muscle relaxant with anti-cholinergic (anti-muscarinic) and anti-histaminic effects which is used to alleviate painful muscle spasm 9 . Dantrolene sodium (DAN), chemically named 1-[[5-(p-Nitrophenyl)furfurylidene]amino]hydantoin sodium salt hydrate, is a directly acting skeletal muscle relaxant which is used intravenously for treating and preventing malignant hyperthermia and related conditions, such as neuroleptic malignant syndrome, and also orally for controlling muscle spasticity 10 , 11 .…”

Insights into the reactivity properties, docking, DFT and MD simulations of orphenadrinium dihydrogen citrate in different solvents

“…It is primarily eliminated through kidneys [3]. As a result, its potential for testing in the treatment of muscle cramps caused by liver cirrhosis appears rational [4,5]. A few clinical researches on the effects of orphenadrine and paracetamol on myalgia found that the pain relieving effect was boosted [6].…”