Category: Formulation and Quality
Purpose: One of the many acetaminophen products available OTC, is a 650 mg extended-release (ER) tablet. The purpose of this study was to screen and compare the dissolution performance of multiple OTC ER products against USP monograph specifications and versus the innovator, Tylenol® product.
Methods: Dissolution of nine different 650 mg ER acetaminophen tablet products purchased from various retail sources was tested according to the USP monograph for acetaminophen extended-release tablets: USP 2 apparatus, 900 mL simulated gastric fluid (SGF) without enzymes @ 37ºC, and 50 rpm paddle speed (n=6). One mL samples of dissolution media were taken at 15, 30, 60, 120, and 180 minutes and analyzed for acetaminophen concentrations using a modification of the HPLC method in the USP monograph for assay of acetaminophen extended-release tablets. Dissolution results were evaluated for conformance with dissolution requirements of the USP monograph.
Results: Dissolution of all nine products conform to the L1 level (n=6) dissolution acceptance criteria for extended-release dosage forms at the prescribed 15 and 60 minutes test times. Except for the Tylenol® product, none of the tested products met the L1 level, requirements of no individual value < 85% @ 180 minutes with more than one individual tablet outside the tolerance range. Without proceeding to L2 testing (n+12), one of the products would already fail the L2 level acceptance criteria with at least one tablet dissolution falling > 10% of labeled content below 85% at the final test time of 180 minutes. The Tylenol® ER product was the only one tested that met the USP dissolution requirements at all specified time points. Even though Tylenol® ER was the only product to meet dissolution requirements at L1, the dissolution profiles of all other products demonstrated similarity to the Tylenol® profile as evidenced by the calculated Similarity Factors (f2) of those profiles vs Tylenol®.
Conclusion: Out of nine different OTC acetaminophen 650 mg ER tablet products tested, only the Tylenol® product met the L1 level dissolution specifications stated in the USP monograph for acetaminophen extended-release tablets. Regardless of this difference in compliance with USP dissolution requirements at L1 (n=6). All of dissolution profiles of the eight other products demonstrated similarity (f2) to the Tylenol® product and, hence, likely no difference in bioavailability between the products.
Braden Crocco– Knoxville, Tennessee