Introduction: Alpha-lipoic acid (ALA) is a bioactive compound marketed as a dietary supplement (DS) worldwide. Methods: This study assessed the quality of nine commercial ALA DS formulations (seven hard capsules, two gastroresistant capsules) from the Serbian market using European Pharmacopoeia tests for solid dosage forms: uniformity of mass (2.9.5), content determination by UV-Vis spectrophotometry, disintegration (2.9.1), and dissolution (2.9.3) in 0.5% sodium lauryl sulfate medium at 37 degrees C (United States Pharmacopeia apparatus 1 [basket], 900 mL, 100 rpm). Results: Measured ALA content ranged from 77.79% to 120.39% of the declared amount, with notable intrabatch variability in some products. Five formulations failed at least one test: two failed uniformity of mass (C, D), two failed content uniformity (B, D), one did not disintegrate within 30 min (H), and three failed dissolution criteria (B, F, H). Our findings reveal an inconsistent quality of ALA DS. Conclusion: There is a need for a transparent and credible quality signal that would inform consumers, guide clinicians, and motivate manufacturers to meet higher standards and more consistent product performance.
Introduction: The advancement of modified-release pharmaceutical forms, such as bentonite-based suppositories, requires accurate modeling of the active ingredient's release kinetics. This study aimed to evaluate the capacity of four canonical release-kinetics models (Weibull, Higuchi, first-order, and Korsmeyer-Peppas) to define and describe the release profile of tramadol from bentonite-based suppository mixtures. Methods: Seventeen bentonite-based tramadol suppository mixtures were prepared according to a design comprising polyethylene glycol (PEG) and bentonite. All dissolution profiles were acquired using a USP basket apparatus. The release-kinetics models were fitted within both frequentist and Bayesian hierarchical frameworks. The frequentist analysis employed Akaike information criterion (AIC)-based selection to rank model performance, and the Bayesian approach incorporated informative priors and a hierarchical structure to capture intermixture variability. The comparison of the models employed leave-one-out cross-validation (LOO) and the widely applicable information criterion (WAIC). Results: The frequentist and Bayesian approaches both identified the Weibull model as the most suitable descriptor of the release behavior for tramadol. The Weibull model showed better performance in describing tramadol release. The hierarchical Bayesian method proposes many advantages in terms of uncertainty quantification and robustness. The complementary use of frequentist and Bayesian techniques offers a rigorous paradigm for sustained-release mixture development. Conclusion: Our study affirms the applicability of bentonite as a biocompatible, functional excipient for modifying drug release behavior of suppositories.
Dissolution testing is a foundational analytical tool in pharmaceutical development, critical for assessing the quality and performance of various dosage forms. Despite its long-standing role, the field is hampered by widely held myths and legacy practices that can jeopardize data integrity and hinder efficient development. This article, authored by the International Consortium for Innovation and Quality in Pharmaceutical Development (IQ) dissolution working group, systematically examines and dispels persistent misconceptions underlying common laboratory practices when testing oral dosage forms using the basket or paddle dissolution apparatus. Key areas addressed include myths about dissolution media selection, such as the inappropriate use of sonication for deaeration and assumptions about universal surfactant concentrations. The authors challenge default approaches to hydrodynamics, including paddle speeds and apparatus configurations, and highlights the necessity of method optimization tailored to each formulation. Additionally, misunderstandings relating to filters, sinkers, sampling techniques, and the transferability of methods between product strengths or populations are critically evaluated. By presenting technical evidence, the authors highlights the risks of relying solely on empirical approaches without establishing a sound scientific understanding of the dissolution behavior of the product. The article underscores the importance of adaptability, thorough validation, and robust rationale in dissolution method development, enabling greater discrimination and clinical relevance. Through myth-busting and evidence-based recommendations, this review aims to foster critical thinking and continuous improvement among pharmaceutical scientists. By dispelling outdated beliefs and promoting rigorous science, this article supports the development of dissolution methods that are reliable, discriminative, and ultimately supportive of both innovation and patient safety.
Introduction: This study aimed to establish a dissolution method for tofacitinib citrate tablets to evaluate the consistency of in vitro dissolution with the reference listed drug (RLD) according to the Chinese Pharmacopoeia. Methods: Dissolution tests were conducted using a basket apparatus at 100 rpm with 900 mL of 0.1 mol/L hydrochloric acid solution, pH 4.5 acetate buffer, pH 6.8 phosphate buffer, and water as dissolution media. The experiments were performed on two fully automated dissolution systems, Agilent and Sotax. Dissolution was analyzed using high-performance liquid chromatography (HPLC), and the dissolution profiles were compared for consistency. Results: The results of the method validation met the requirements for dissolution testing. The method exhibited strong specificity, good linearity, no membrane adsorption, excellent precision, high accuracy, good solution stability, and robustness. Cumulative dissolution of both the test and RLD tablets exceeded 85% within 15 minutes in all four dissolution media, and their dissolution profiles were consistent. Conclusion: This study developed and validated a method to determine the dissolution of tofacitinib citrate tablets, which serves as a suitable approach for in vitro consistency evaluation.
Introduction: The study was designed to assess the in vitro dissolution behavior, similarity, and drug release kinetics of a bilayer fixed-dose combination (FDC) tablet containing efonidipine hydrochloride ethanolate (Efo), chlorthalidone (Chlor), and telmisartan (Telmi). Dissolution performance was compared with that of the corresponding reference products. Methods: A regulatory-focused, multimedia dissolution strategy was designed to evaluate the release characteristics of all three active pharmaceutical ingredients under conditions reflecting gastrointestinal pH variability. Dissolution testing was conducted in acid buffer (pH 1.2), acetate buffer (pH 4.5), phosphate buffer (pH 6.5) containing 0.5% Tween 80 for Efo and Chlor, and phosphate buffer (pH 7.5) for Telmi. The study was performed for two FDC strengths (Efo + Chlor + Telmi: 40 mg + 6.25 mg + 40 mg and 40 mg + 12.5 mg + 40 mg) to ensure consistency of release performance across dosage variants. Results: Efo showed negligible release in pH 1.2 and 4.5 media due to poor solubility, whereas Chlor demonstrated rapid and complete dissolution across all conditions. Telmi exhibited marked pH-dependent solubility; incorporation of alkalizers significantly enhanced its release, achieving nearly complete dissolution in phosphate buffer. Model-independent analysis using f1 and f2 factors confirmed similarity between test and reference formulations for all APIs in the selected media. Dissolution efficiency, mean dissolution time, and mean dissolution rate were comparable. Kinetic modeling indicated Korsmeyer-Peppas release for Efo and Chlor, and Weibull release behavior for Telmi in both formulations. Conclusion: The findings indicate similar dissolution characteristics and underlying release kinetics, confirming pharmaceutical equivalence of the test FDC tablet with the reference products and establishing its appropriateness for regulatory evaluation and routine quality control.
