In vitro Characterization and Evaluation of Commercialized Paracetamol Products in Jordan

Abstract

Paracetamol (acetaminophen) is one of the most commonly used antipyretic and analgesic drugs worldwide. It is the drug of choice for patients with bronchial asthma, hemophilia, salicylate hypersensitivity, peptic ulcer, and pregnant or breastfeeding women who cannot be treated with nonsteroidal anti-inflammatory drugs. It is marketed and manufactured by many pharmaceutical companies, which necessitates the requirement of quality control investigation. A post-market evaluation was conducted on five commercial paracetamol products (500 mg) available in Jordan, which involved quality control testing in terms of dissolution, disintegration, weight variation, and glass transition temperature (Tg) determination using dynamic mechanical thermal analysis (DMTA). Dissolution and disintegration of the five products were compared under two different conditions, compendial United States Pharmacopeial Convention (USP) and non-compendial. Compendial experiments were conducted under pH 5.8, and non-compendial testing was carried out under pH 1.2. Results revealed variations in the dissolution patterns at the different pH conditions for the same formulation. Generally, faster dissolution was observed when testing the dissolution in compendial USP conditions; pH 5.8 compared to pH 1.2. Disintegration was also affected by pH in the tested formulations. Tg detected via DMTA of the tested formulation was ranged from 18.82 ± 0.77 °C to 23.13 ± 2.46 °C. No correlation was found between Tg variation and drug dissolution. In general, all products met the compendial requirements despite their differences in the early stages of dissolution profiles. Our work highlights the importance of post-market quality control testing of generic equivalents of immediate release dosage forms, which is essential for improving upon existing formulations. It also introduces DMTA as an informative tool for detecting thermal transitions of active pharmaceutical ingredients (APIs) in solid oral dosage forms.