The current studies entail quality by design (QbD)-enabled development of a simple, rapid, precise, accurate, and cost-effective high-performance liquid chromatographic method for estimation of metformin hydrochloride (M-HCl). Design of experiments (DoE) was applied for multivariate optimization of the experimental conditions of the HPLC method. Risk assessment was performed to identify the critical method parameters (CMPs) using Ishikawa diagram. The factor screening studies were performed using a two-factor three-levels design. Two independent factors, buffer pH and mobile phase composition, were used to design mathematical models. Central composite design (CCD) was used to study the response surface methodology and to study in depth the effects of these independent factors, thus evaluating the critical analytical attributes (CAAs), namely, retention time, peak area, and symmetry factor as the parameters of method robustness. Desirability function was used to simultaneously optimize the CAAs. The optimized and predicted data from contour diagram consisted of 0.02 M acetate buffer pH = 3/methanol in a ratio of 70/30 (v/v) as the mobile phase with a flow rate 1 mL/min. The separation was made on a Thermoscientific ODS Hypersyl^TM chromatographic column (250 × 4.6 mm, 5 μm) with oven temperature 35 °C and UV detection at 235 nm. The optimized assay conditions were validated according to ICH guidelines. Hence, the results clearly showed that QbD approach could be successfully applied to optimize HPLC method for estimation of M-HCl. The method was applied both for the evaluation of M-HCl content in tablets, and for in vitro dissolution studies of M-HCl from conventional and prolonged-release tablets.

Background/Objectives: Mesoporous silica materials, particularly KIT-6, offer promising features, such as large surface area, tunable pore structures, and biocompatibility, making them ideal candidates for advanced drug delivery systems. The aims of this study were to develop and evaluate an innovative modified-release platform for metformin hydrochloride (MTF), using KIT-6 mesoporous silica as a matrix, to enhance oral antidiabetic therapy. Methods: KIT-6 was synthesized using an ultrasound-assisted sol-gel method and subsequently loaded with MTF via adsorption from alkaline aqueous solutions at two concentrations (1 and 3 mg/mL). The structural and morphological characteristics of the matrices—before and after drug loading—were assessed using SEM-EDX, TEM, and nitrogen adsorption–desorption isotherms (the BET method). In vitro drug release profiles were recorded in simulated gastric and intestinal fluids over 12 h. Kinetic modeling was performed using seven classical models, and a multifractal theoretical framework was used to further interpret the complex release behavior. Results: The loading efficiency increased with increasing drug concentration but nonlinearly, reaching 56.43 mg/g for 1 mg/mL and 131.69 mg/g for 3 mg/mL. BET analysis confirmed significant reductions in the surface area and pore volume upon MTF incorporation. In vitro dissolution showed a biphasic release: a fast initial phase in an acidic medium followed by sustained release at a neutral pH. The Korsmeyer–Peppas and Weibull models best described the release profiles, indicating a predominantly diffusion-controlled mechanism. The multifractal model supported the experimental findings, capturing nonlinear dynamics, memory effects, and soliton-like transport behavior across resolution scales. Conclusions: The study confirms the potential of KIT-6 as a reliable and efficient carrier for the modified oral delivery of metformin. The combination of experimental and multifractal modeling provides a deeper understanding of drug release mechanisms in mesoporous systems and offers a predictive tool for future drug delivery design. This integrated approach can be extended to other active pharmaceutical ingredients with complex release requirements.

Background: Rheumatoid arthritis is a chronic autoimmune disease that leads to severe disability and requires improved therapeutic strategies to optimize anti-inflammatory treatment. This study aimed to address this challenge by developing and characterizing an extended-release polymer matrix tablet containing ketoprofen and a ketoprofen–β-cyclodextrin complex with enhanced therapeutic properties. The objective was to improve inflammation management and therapeutic outcomes using a novel delivery system based on the inclusion of the active substance in cyclodextrin complexes. Methods: Tablets were formulated using ketoprofen and ketoprofen–β-cyclodextrin complexes combined with hydrophilic polymers such as Carbopol^® 971P NF, Kollidon^® VA 64, and Methocel^TM K4M. The complexes were obtained via the coprecipitation method to improve bioavailability. The kinetics of the release of ketoprofen, ketoprofen–β-cyclodextrin complex (2:1), and ketoprofen–β-cyclodextrin complex (1:1) from the tablets were investigated in vitro in artificial gastric and intestinal fluids, and drug release profiles were established. Advanced mathematical models were used to describe the nonlinear behavior of the drug–polymer systems. Results: The inclusion of ketoprofen in the β-cyclodextrin complexes was confirmed, revealing distinct release profiles. Tablets (K-3 F-3) containing the 1:1 complex showed rapid release (96.2% in 4–7 h), while tablets (K-1 F-4) containing free ketoprofen released 76% over 9–11 h. Higher polymer concentrations slowed the release due to gel barrier formation. Pharmacotechnical and stability tests supported their suitability as extended-release forms. A multifractal modeling approach described the release dynamics, treating the polymer–drug matrix as a complex system, with release curves characterized by variations in the fractal dimension and resolution. Conclusions: Specific hydrophilic polymer combinations effectively prolonged ketoprofen release. The developed matrix tablets, which were evaluated via in vitro studies and mathematical modeling, show promise for improving therapeutic outcomes and patient compliance during rheumatoid arthritis treatment.

Background: Diabetes is a growing global health crisis that requires effective therapeutic strategies to optimize treatment outcomes. This study aims to address this challenge by developing and characterizing extended-release polymeric matrix tablets containing metformin hydrochloride (M-HCl), a first-line treatment for type 2 diabetes, and honokiol (HNK), a bioactive compound with potential therapeutic benefits. The objective is to enhance glycemic control and overall therapeutic outcomes through an innovative dual-drug delivery system. Methods: The tablets were formulated using hydrophilic polymers, such as Carbopol^® 71G NF and Noveon^® AA-1. The release kinetics of M-HCl and HNK were investigated through advanced mathematical models, including fractal and multifractal dynamics, to capture the non-linear and time-dependent release processes. Traditional kinetic models (zero-order, first-order, Higuchi equations) were also evaluated for comparison. In vitro dissolution studies were conducted to determine the release profiles of the active ingredients under varying polymer concentrations. Results: The study revealed distinct release profiles for the two active ingredients. M-HCl exhibited a rapid release phase, with 80% of the drug released within 4–7 h depending on polymer concentration. In contrast, HNK demonstrated a slower release profile, achieving 80% release after 9–10 h, indicating a greater sensitivity to polymer concentration. At shorter intervals, drug release followed classical kinetic models, while multifractal dynamics dominated at longer intervals. Higher polymer concentrations resulted in slower drug release rates due to the formation of a gel-like structure upon hydration, which hindered drug diffusion. The mechanical properties and stability of the matrix tablets confirmed their suitability for extended-release applications. Mathematical modeling validated the experimental findings and provided insights into the structural and time-dependent factors influencing drug release. Conclusions: This study successfully developed dual-drug extended-release matrix tablets containing metformin hydrochloride and honokiol, highlighting the potential of hydrophilic polymers to regulate drug release. The findings emphasize the utility of advanced mathematical models for predicting release kinetics and underscore the potential of these formulations to improve patient compliance and therapeutic outcomes in diabetes management.

Background: Oromucosal films are thin polymeric dosage forms designed to hydrate rapidly in the oral cavity and enable local or systemic drug delivery. Their performance depends on coupled processes including wetting, swelling, polymer relaxation, matrix softening, and structural failure. Because these phenomena depend strongly on the formulation composition and polymer-network organization, a mechanistic framework linking conventional characterization data to film performance is needed. This study aimed to develop a Madelung-type multifractal swelling–disintegration–release-readiness model for chitosan/hydroxypropyl methylcellulose (HPMC) films and to examine its relevance using a twelve-formulation experimental series. Methods: Twelve films based on chitosan (film-forming polysaccharide), HPMC K-4M (hydrophilic swelling polymer), glycerin (plasticizer), and starch (disintegrant) were prepared via solvent casting. The films were characterized for loss on drying, surface pH, mass and thickness uniformity, wetting time, swelling behavior, structural-disintegration onset, elongation response, rupture resistance, folding endurance, and surface roughness. The proposed model described water uptake, swelling-front motion, matrix integrity, local release-readiness activation, and hydration-induced loading as coupled fields across the film thickness. Results: Formulation markedly influenced hydration behavior, mechanical performance, structural stability, and surface morphology. Films F2 and F7 emerged as the most promising complementary unloaded matrix platforms for future active-compound incorporation and experimental release evaluation. F2 behaved as a high-swelling, mechanically stable starch-free matrix, whereas F7 combined faster wetting, starch-assisted structural destabilization, and favorable flexibility. Conclusions: This framework provides a quantitative link between empirical film characterization and formulation-level mechanistic interpretation. It translates conventional characterization parameters into descriptors related to the apparent water penetration, swelling capacity, matrix-failure tendency, mechanical suitability, and structural heterogeneity. The present results support candidate selection for future Active Pharmaceutical Ingredient-loaded studies but do not constitute validation of drug-release kinetics.

Ketoprofen is a Biopharmaceutics Classification System (BCS) class II non-steroidal anti-inflammatory drug whose therapeutic performance is limited by its poor aqueous solubility, though complexation with cyclodextrins is a well-established strategy to overcome this limitation. The aim of this work was to prepare and characterize inclusion complexes of ketoprofen with HPβCD. Complexes were obtained by the solution (magnetic-stirring) method at ketoprofen–HPβCD molar ratios of 1:1 and 2:1 and were characterized by Fourier-transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), scanning electron microscopy (SEM) coupled with EDX, and computer-assisted dimensional analysis and statistics (AutoCAD/MathCAD). The bulk and tapped densities were used to derive the Carr index and the Hausner ratio, respectively. FT-IR showed attenuation and shifting of the characteristic C=O, C=C, and –CH bands of ketoprofen and the presence of the 1655 cm⁻¹ band in complexes demonstrates inclusion. DSC revealed a marked reduction of the ketoprofen melting endotherm, the degree of inclusion reaching 75% (1:1) and 62% (2:1). SEM and statistical analysis confirm, individualized particles, predominantly 20–100 µm in perimeter size. The dissolution test showed a faster release of the complexes than in the case of pure ketoprofen. Therefore, HPβCD forms stable inclusion complexes with ketoprofen having pharmacotechnical properties suitable for compressed tablets.