This manuscript highlights key sessions from the In Vitro Release and Dissolution Testing (IVRDT) and Oral Biopharmaceutics and Absorption Modeling (OBAM) communities at the 2025 AAPS PharmSci 360 Annual Meeting (November 9-12, San Antonio, TX). Presentations emphasized a shift toward mechanistic and predictive in vitro and silico tools, including enzymatic dissolution media, physics-based particle dissolution modeling, physiologically based biopharmaceutics modeling (PBBM) applications for food-effect assessment and specification setting, advanced gastrointestinal simulation platforms, AI-driven formulation optimization, and the complementary role of preclinical animal studies. Collectively, these sessions underscored the value of integrating biorelevant experimentation with computational modeling to streamline and de-risk oral drug development.
This bibliometric study explores the multifaceted domain of the dissolution of solid oral pharmaceutical forms, focusing on key aspects such as dissolution testing, dissolution profiling and modeling, and comparative dissolution tests for therapeutic equivalence over the past 40 years (1982-2025). The pharmaceutical quality system hinges on controlling the product and process elements. Dissolution tests are critical for bioperformance and therapeutic equivalence, necessitating mastery of this domain and the influencing factors. Traditionally, these procedures rely on liquid chromatography and UV-visible spectroscopy, which are often cumbersome and generate significant waste. However, innovative techniques such as artificial intelligence, machine learning, and chemometrics are gaining prominence, especially in research laboratories and institutions involved in pharmaceutical development. Pharmacopoeias contain general chapters on chemometrics and associated guidelines, including those from the Official Medicines Control Laboratories (OMCL) network, which develops chemometric tools for quality control, even for counterfeit products. Regulatory bodies like the ICH and authorities in developed countries encourage the pharmaceutical industry to adopt next-generation practices, including quality by design (QBD), process analytical technology (PAT), and continuous manufacturing. The development of increasingly complex drugs drives the adoption of new tools to address performance, structural complexity, excipient effects, and multicomponent formulations. These innovations aim to enhance the precision and efficiency of dissolution methods while reducing environmental impact and associated costs. Integrating advanced tools like chemometrics allows researchers to obtain more reliable results and optimize drug development processes. The future of the pharmaceutical industry relies on adopting these cutting-edge technologies to ensure superior product quality and meet growing regulatory demands.
Introduction: Generic medicines, including the World Health Organization (WHO) prequalified products, aim to ensure access to affordable products that are comparable to innovator products in terms of quality, safety, and efficacy. A comparative in vitro and in vivo evaluation of generic products against the reference listed drug (RLD) forms a basis of product development and regulatory approval. This study investigated the in vitro dissolution of azithromycin tablets (Zithromax, Pfizer), from different regulated markets. Methods: Four lots of Zithromax RLD tablets were procured from regulated markets in Switzerland, Germany, and Singapore at different time points. Dissolution testing was performed using a paddle apparatus operated at 75 rpm for 60 minutes with 900 mL of four different media: hydrochloric acid (HCl) pH 1.2, acetate buffer pH 4.5, phosphate buffer pH 6.8, and United States Pharmacopeial phosphate buffer (pH 6.0). Dissolution profiles were compared using the similarity factor (f(2)) and one-way analysis of variance (ANOVA). Results: Dissolution profiles of all lots in the official medium (pH 6.0) were similar (f(2) > 50). However, at pH 4.5 and 6.8, pairwise comparisons among lots revealed dissimilarity for some lot pairs (f(2) < 50). In acidic conditions (0.1 N HCl, pH 1.2), all lots exhibited progressive degradation. One-way ANOVA of the dissolution profiles revealed no statistically significant differences (p > 0.05). Conclusion: Variability in dissolution profiles of Zithromax RLD tablets sourced from regulated markets highlights the challenges in selecting an appropriate comparator for generic product development. Such variability may complicate formulation development and delay the regulatory pathways, including the WHO prequalification, particularly for manufacturers in resource-limited settings.
Introduction: Ritonavir (RIT) is classified as a BCS class IV drug due to its poor solubility and limited permeability. The goal of this study was to utilize a model-independent method to compare the dissolution profiles of branded (B-1) and generic (G1-G5) Ritonavir tablets currently marketed in India. Methods: USP apparatus 2 (paddle, 75 rpm) with 0.06 M polyoxyethylene-10 lauryl ether as the dissolution medium (37.0 +/- 0.5 degrees C) provided the optimal conditions for testing. Although the primary focus was the model-independent technique, a concurrent investigation of the model-dependent strategy was used for comparison. Analytical method development with validation was also performed. Results: The difference factor (f1) value, similarity factor (f2), and percentage of drug release fell within the acceptable range for all products except one (G-4: f1 18.0, f2 42.1). When compared with the reference product (B-1), G-5 was the most suitable (f1 3.4, f2 74.5) and considered fully interchangeable. Conclusion: The validated analytical method is suitable for future industry adoption for routine analytical testing of RIT tablets. The dissolution profiles obtained under these conditions demonstrated capability for comparative assessment.
Background: Furosemide, a BCS class IV diuretic, demonstrates inadequate water solubility and restricted intestinal permeability, leading to suboptimal oral bioavailability. Enhancing its dissolution is essential for improving therapeutic efficacy. This study assessed the effect of lyophilization on the in-vitro solubility profile of furosemide relative to the pure drug, Lasix (reference product), and a commercially available generic formulation. Methods: A lyophilized formulation of furosemide was developed using sucrose as a cryoprotectant and subjected to freeze-drying under regulated circumstances. Dissolution testing was conducted with a USP type 2 paddle apparatus in 0.1 N HCl, and drug concentrations were measured via UV-Vis spectrophotometry (Amax = 229 nm). Dissolution kinetics were analyzed using the Korsmeyer-Peppas model, and the dissolution profiles were evaluated with the difference factor (f1). Results: The lyophilized formulation exhibited markedly superior solubility relative to the other formulations. Kinetic release adhered to a Fickian diffusion mechanism (n = 0.051), having enhanced porosity and partial amorphization. Conversely, the pure drug demonstrated a more gradual release profile (n = 0.667). The f1 value between Lasix and the lyophilized formulation was above 160, signifying considerable dissimilarity. Conclusion: Lyophilization significantly enhanced the solubility of furosemide by altering its physicochemical properties. Nonetheless, owing to the significant disparities in dissolution patterns, further bioequivalence and pharmacokinetic investigations are necessary to validate clinical interchangeability.
This USP guideline represents the current best practices for determining mechanical qualification performance for USP apparatus 3, described in Dissolution <711>. The guideline covers the performance qualification topics of environment, benchtop levelness, assembly, apparatus conformance, alignments, drive system and transmission, temperature control, component certification, periodic preventative maintenance, physical parameter measurement, and operational checks. This guideline is intended to provide information that aids the dissolution laboratory in establishing appropriate standard operating procedures to verify compliance with compendial requirements and ensure valid dissolution and drug release testing results. USP welcomes proposals for a drug product that could be used as a final performance qualification to assess the overall suitability of the equipment.
Introduction: Folic acid (FA) deficiency can be associated with various pathophysiological conditions, altering the homeostasis of the human organism. This study addresses the unique analytical challenges of FA quantification in hard capsules, a less-studied oral solid dosage form compared to tablets. The evaluation of quality, safety, and efficacy is essential to ensure that this product meets the characteristics described in the pharmacopoeia to guarantee biopharmaceutical and pharmacotherapeutic performance. This study aimed to develop and validate an analytical method for the quantification of FA in capsules using ultraviolet-visible absorption spectrophotometry. Methods: Starch and microcrystalline cellulose were selected as excipients for the preparation of capsules containing 5 mg of FA. Parameters such as selectivity and matrix effect, linearity, precision, accuracy, limit of detection (LD), limit of quantification (LQ), and robustness were evaluated according to RDC no. 166/2017. Later, weight determination, assay, content uniformity, and dissolution tests were conducted. Results: The method displayed high selectivity in pH 7.2 at 280 nm, with no matrix effect. Statistical treatment of the linearity (r = 0.9998, from 1.0-15 mu g/mL) confirmed homoscedasticity of the data, showing a normal distribution (p > 0.05) and independence of residues. Precision, accuracy, LD (0.249 mu g/mL), LQ (0.755 mu g/mL), and robustness to wavelength and temperature variations were suitable. The capsules showed satisfactory results for weight determination (limits of variation of +/- 10.0%, RSD (3%), and variation of theoretical content (96-101%). The validated analytical method demonstrated applicability in the quantification of FA encapsulated for the assay (96.3%), content uniformity (AV = 7.0), and dissolution tests (103%) using basket as apparatus, and phosphate buffer as dissolution medium. Conclusion: This method offers a cost-effective alternative for routine quality control of FA capsules, particularly in resource-limited settings. Though it is essential to validate the conditions used in the dissolution test.
Introduction: Salt formulations are widely used in the pharmaceutical industry to increase drug solubility and accelerate dissolution. In this work, the enhancing effect of salt formulations on the absorption rate of ibuprofen was investigated in both the fasted and fed states, using biorelevant dissolution testing. Methods: The dissolution behavior of two different ibuprofen salts was studied using two commercially available formulations: Dolormin, containing the lysinate salt of ibuprofen, and Spedifen, containing the arginate salt. Their dissolution was compared to that of the orodispersible tablet formulation containing the free acid (Nurofen) at different dose levels in both single and two-stage dissolution tests. Results: When administered in the fasted state, the rapid onset of action of the pharmaceutical salt formulations is directly related to their dissolution behavior, highlighting the importance of choosing suitable dissolution media and methodology to link in vitro with in vivo data. In the fed state, gastric emptying becomes rate-limiting to absorption, such that even fast-dissolving products are not able to provide a short onset of action. Conclusion: Biorelevant dissolution delivers key data for determining pharmaceutical salt formulation effects on dissolution in the fed and fasted states.
Introduction: Sulindac is a non-steroidal anti-inflammatory drug (NSAID) primarily used to alleviate pain and inflammation associated with various arthritides (e.g., rheumatoid arthritis, osteoarthritis) and soft tissue injuries. To ensure consistent drug release and therapeutic efficacy, a reliable dissolution method must be established for quality control. This research systematically investigates and validates the dissolution method for sulindac tablets. Methods: The 0.2-g strength was selected for dissolution method validation, including investigation of specificity, linear range, filter membrane adsorption, accuracy, precision, robustness, stability, and recovery rate. Dissolution profiles for self-made tablets (0.1 g and 0.2 g) and the reference listed drug (RLD) were evaluated in multiple dissolution media (0.1 mol/L hydrochloric acid, pH 4.5 acetate buffer, and pH 6.8/pH 7.2 phosphate buffer). Results: The dissolution method validation demonstrated that all indicators met the requirements, including no interference from blanks, a good linear relationship, negligible membrane adsorption, excellent precision and stability, a satisfactory recovery rate, and strong robustness. In phosphate buffer (pH 6.8 and 7.2), the dissolution profiles of the test products and RLDs were similar (f(2) > 50). Conclusion: The validated dissolution method is accurate and reliable, effectively facilitating the dissolution testing and quality evaluation of sulindac tablets.
Introduction: Analysis of the dissolution process is becoming more prevalent, including fitting mathematical models to describe dissolution profiles. This paper presents the development of RKinetDS, an open-source software for fitting drug dissolution curves to mathematical models. Methods: The software was written in R (version 4.2.3), and the graphical user interface was developed using the Shiny R package. RKinetDS currently includes 36 dissolution models. The software uses various measures to evaluate the goodness of fit including RMSE, R2, R2adjusted, and Akaike Information Criterion (AIC). To evaluate the reliability and practical applicability of the RKinetDS, its performance was assessed using real-world dissolution datasets sourced from published studies to reflect different experimental conditions and formulation types. RKinetDS was used to replicate the model fits. Results: RKinetDS produced results that were similar to those reported in published studies for tablets, oral suspension, and microspheres. For tablets, the best fit was the Weibull model (Castro et al.: (3 = 0.6238, R2 = 0.9998; RKinetDS: (3 = 0.8146, R2 = 0.9999). For oral suspension, Weibull model was the best fit as well (de Silva et al: (3 = 0.2900, R2 = 0.9513; RKinetDS: (3 = 0.2101, R2 = 0.9958). For microspheres, the Korsmeyer-Peppas model was most suitable (Murtaza et al.: K = 18.191, n = 0.487, R2 = 0.9891; RKinetDS: K = 15.228, n = 0.5439, R2 = 0.9841). Conclusion: RKinetDS is distinguished by advanced optimizers that enhance its ability to fit the most suitable models, a modern interface that simplifies navigation within the software, and extensive reporting options. RKinetDS supports the dosage form development process in academia and industry. RKinetDS is freely available on GitHub (github.com/ AleksanderMendyk/RKinetDS_deploy) and the shinnyapps.io platform (jszlek.shinyapps.io/RKinetDS).
