Search Results (37)

Background/Objectives: Reflecting the interaction between dissolution and absorption, the biphasic dissolution system is an appealing approach for estimating the intestinal absorption of drugs in humans. The study aims to characterize the suitability of the biphasic in vitro dissolution testing to set up an in vitro–in vivo correlation (IVIVC) for the original and generic immediate-release (IR) tablets of a Biopharmaceutics Classification System (BCS) Class II drug, bicalutamide (BIC). Methods: USP apparatus II paddle was used to conduct dissolution testing. A level A IVIVC was obtained between in vitro partitioning and in vivo absorption data of the original drug. The single-compartmental modeling was used for pharmacokinetic (PK) analysis. The generic product’s plasma concentrations were estimated. Results: There was a good correlation between in vitro and in vivo data (r² = 0.98). The area under the concentration–time curve (AUC) and maximum plasma concentration (C_max) ratios for generic/original were 1.04 ± 0.01 and 0.951 ± 0.026 (mean ± SD), respectively. Conclusions: The biphasic dissolution testing may present an in vivo predictive tool for developing generic products of poorly soluble and highly permeable drugs such as BIC, which are characterized by pH-independent poor solubility. Full article

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. Full article

Magnesium whitlockite (Mg-WH) has emerged as a promising biomaterial for bone regeneration due to its compositional similarity to natural bone minerals. This study aimed to systematically modify a dissolution–precipitation synthesis method to produce Mg-WH granules with tailored morphologies and controlled phase compositions for possible use in bone regeneration applications. Three distinct precursor granules were prepared by mixing varying amounts of ammonium dihydrogen phosphate and magnesium hydrogen phosphate with calcium sulfate. The precursors were then transformed into biphasic and single-phase Mg-WH granules by means of immersion in magnesium- and phosphate-containing solutions under controlled conditions. The X-ray diffraction results demonstrated that biphasic materials containing Mg-WH and either calcium-deficient hydroxyapatite (CDHA) or dicalcium phosphate anhydrous (DCPA) formed after 24 h of synthesis, depending on the synthesis conditions. Prolonging the reaction time to 48 h resulted in complete transformation into single-phase Mg-WH granules. Fourier-transform infrared spectroscopy confirmed the presence of functional groups characteristic of Mg-WH, CDHA, and DCPA in the intermediate products. The spectra also indicated the absence of precursor phases and the progressive elimination of secondary phases as the reaction time increased. Scanning electron microscopy analyses revealed notable morphological transformations from the raw granules to the product granules, with the latter exhibiting interlocked spherical and rod-like particles composed of fine Mg-WH rhombohedral crystals. N₂ adsorption–desorption analyses exposed significant differences in the surface properties of the synthesized granules. By varying precursor, reaction solution compositions, and reaction times, the study elucidated the phase evolution mechanisms and demonstrated their impact on the structural, morphological, and surface properties of Mg-WH granules. Full article

The increasing demand for lithium-ion batteries (LIBs) and their limited lifespan emphasize the urgent need for sustainable recycling strategies. This study investigates the application of tetrabutylphosphonium-based ionic liquids (ILs) as alternative leaching agents for recovering critical metals, Li(I), Co(II), Ni(II), and Mn(II), from spent NMC cathode materials. Initial screening experiments evaluated the leaching efficiencies of nine tetrabutylphosphonium-based ILs for Co(II), Ni(II), Mn(II), and Li(I), revealing distinct metal dissolution behaviors. Three ILs containing HSO₄⁻, EDTA²⁻, and DTPA³⁻ anions exhibited the highest leaching performance and were selected for further optimization. Key leaching parameters, including IL and acid concentrations, temperature, time, and solid-to-liquid ratio, were systematically adjusted, achieving leaching efficiencies exceeding 90%. Among the tested systems, [TBP][HSO₄] enabled near-complete metal dissolution (~100%) even at room temperature. Furthermore, an aqueous biphasic system (ABS) was investigated utilizing [TBP][HSO₄] in combination with ammonium sulfate, enabling the complete extraction of all metals into the salt-rich phase while leaving the IL phase metal-free and potentially suitable for reuse, indicating the feasibility of integrating leaching and extraction into a continuous, interconnected process. This approach represents a promising step forward in LIB recycling, highlighting the potential for sustainable and efficient integration of leaching and extraction within established hydrometallurgical frameworks. Full article

Background/Objectives: This study aimed to develop gastroretentive tablets based on mucoadhesive–floating systems with encapsulated gentian (Gentiana lutea, Gentianaceae) root extract to overcome the low bioavailability and short elimination half-life of gentiopicroside, a dominant bioactive compound with systemic effect. The formulation also aimed to promote the local action of the extract in the stomach. Methods: Tablets were obtained by direct compression of sodium bicarbonate (7.5%) and solid lipid microparticles (92.5%), which were obtained with lyophilizing double emulsions. A quality by design (QbD) was employed to evaluate the impact of formulation factors and processing parameters on emulsion viscosity, powder characteristics (moisture content, encapsulation efficiency, flowability), and tablet characteristics (floating lag time, gentiopicroside release, and assessment of dispersibility during in vitro dissolution). Results: The trehalose content and high-shear-homogenization (HSH) time of primary emulsion were critical factors. Trehalose content positively influenced emulsion viscosity, moisture content, floating lag time, encapsulation efficiency, and the release rate of gentiopicroside. HSH time positively affected powder stability and negatively gentiopicroside release. The selected powder had a high gentiopicroside encapsulation efficiency (95.13%), optimal stability, and good flowability. The developed tablets exhibited adequate floating lag time (275 s), mucoadhesive properties, and gentiopicroside biphasic release (29.04% in 45 min; 67.95% in 6 h). Furthermore, the optimal tablet formulation remained stable for 18 months and was primarily digested by duodenal enzymes. Conclusions: Dual-mechanism gastroretentive tablets with encapsulated gentian root extract were successfully developed. The in vitro digestion study demonstrated that the optimal formulation effectively resisted gastric enzymes, ensuring the release of its contents in the small intestine, even in the case of premature gastric evacuation. Full article

Background: This study explored the potential of MCM-48 mesoporous silica matrices as a drug delivery system for metformin hydrochloride, aimed at improving the therapeutic management of type 2 diabetes mellitus. The objectives included the synthesis and characterization of MCM-48, assessment of its drug loading capacity, analysis of drug release profiles under simulated physiological conditions, and the development of a multifractal dynamics-based theoretical framework to model and interpret the release kinetics. Methods: MCM-48 was synthesized using a sol–gel method and characterized by SEM-EDX, TEM, and nitrogen adsorption techniques. Drug loading was performed via adsorption at pH 12 using metformin hydrochloride solutions of 1 mg/mL (P-1) and 3 mg/mL (P-2). In vitro dissolution studies were conducted to evaluate the release profiles in simulated gastric and intestinal fluids. A multifractal dynamics model was developed to interpret the release kinetics. Results: SEM-EDX confirmed the uniform distribution of silicon and oxygen, while TEM images revealed a highly ordered cubic mesoporous structure. Nitrogen adsorption analyses showed a high specific surface area of 1325.96 m²/g for unloaded MCM-48, which decreased with drug loading, confirming efficient incorporation of metformin hydrochloride. The loading capacities were 59.788 mg/g (P-1) and 160.978 mg/g (P-2), with efficiencies of 99.65% and 89.43%, respectively. In vitro dissolution studies showed a biphasic release profile: an initial rapid release in gastric conditions followed by sustained release in intestinal fluids, achieving cumulative releases of 92.63% (P-1) and 82.64% (P-2) after 14 hours. The multifractal dynamics-based theoretical release curves closely matched the experimental data. Conclusions: MCM-48 mesoporous silica effectively enhanced metformin delivery, offering a controlled release profile well-suited for type 2 diabetes management. The multifractal theoretical framework provided valuable insights into drug release dynamics, contributing to the advancement of innovative drug delivery systems. Full article

Background/Objectives: Drugs exhibiting poor aqueous solubility present a challenge to efficient delivery to the site of action. Spanlastics (a nano, surfactant-based drug delivery system) have emerged as a powerful tool to improve solubility, bioavailability, and delivery to the site of action. This study aimed to better understand factors affecting the physicochemical properties of spanlastics, quantify their effects, and use them to enhance the bioavailability of famotidine (FMT), a model histamine H2 receptor antagonist (BCS class IV). Methods: FMT was incorporated into nano-spanlastics drug delivery system. The ethanol injection method, Box–Behnken design, and mathematical modeling were utilized to fabricate famotidine-loaded nano-spanlastics and optimize the formula. Spanlastics were characterized for their particle size, polydispersity index, zeta potential, entrapment efficiency, drug loading, compatibility of the excipients (using DSC), in vitro drug release, and in vivo pharmacokinetics. Results: Span 60 (the non-ionic surfactant) and tween 60 (the edge activator) gave rise to spanlastics with the best characteristics. The optimal spanlastic formulation exhibited small particle size (<200 nm), appropriate polydispersity index (<0.4), and zeta potential (>−30 mV). The entrapment efficiency and drug loading of the optimum formula assured its suitability for hydrophobic drug entrapment as well as practicability for use. DSC assured the compatibility of all formulation components. The drug release manifested a biphasic release pattern, resulting in a fast onset and sustained effect. Spanlastics also showed enhanced C_max, AUC_0–24, and bioavailability. Conclusions: Spanlastics manifested improved FMT dissolution, drug release characteristics, membrane permeation, and pharmacokinetic behavior. Full article

The porous particles prepared from composited calcium–ortho-phosphate (biphasic), Thai silk fibroin, gelatin, and alginate, with an organic to inorganic component ratio of 15.5:84.5, were tested for their abilities to control the release of the commercialized antibiotic solutions, clindamycin phosphate (CDP) and amikacin sulfate (AMK). The in vitro biodegradability tests complying to the ISO 10993-13:2010 standard showed that the particles degraded <20 wt% within 56 days. The drugs were loaded through a simple adsorption, with the maximum loading of injection-graded drug solution of 43.41 wt% for CDP, and 39.08 wt% for AMK. The release profiles from dissolution tests of the drug-loaded particles varied based on the adsorption methods used. The drug-loaded particles (without a drying step) released the drug immediately, while the drying process after the drug loading resulted in the sustained-release capability of the particles. The model-fitting of drug release profiles showed the release driven by diffusion with the first-ordered kinetic after the initial burst release. The released CDF and AMK from particles could sustain the inhibition of Gram-positive bacteria and Gram-negative bacteria, respectively, for at least 72 h. These results indicated the potential of these composited particles as controlled-release carriers for CDP and AMK. Full article

Skin cancer is threatening more and more people’s health; its postoperative recurrence and wound infection are still critical challenges. Therefore, specialty wound dressings with multifunctional bioactivity are urgently desired. Emodin is a natural anthraquinone compound that has anti-cancer and anti-bacterial properties. Herein, we fabricated coaxial electrospinning nanofibers loaded with emodin to exploit a multifunctional wound dressing for skin cancer postoperative management, which encapsulated emodin in a polyvinylpyrrolidone core layer, combined with chitosan-polycaprolactone as a shell layer. The nanofibers were characterized via morphology, physicochemical nature, drug load efficiency, pH-dependent drug release profiles, and biocompatibility. Meanwhile, the anti-cancer and anti-bacterial effects were evaluated in vitro. The emodin-loaded nanofibers exhibited smooth surfaces with a relatively uniform diameter distribution and a clear shell-core structure; remarkably, emodin was evenly dispersed in the nanofibers with significantly enhanced dissolution of emodin. Furthermore, they not only display good wettability, high emodin entrapment efficiency, and biphasic release profile but also present superior biocompatibility and anti-cancer properties by increasing the levels of MDA and ROS in A-375 and HSC-1 cells via apoptosis-related pathway, and long-term anti-bacterial effects in a dose-independent manner. The findings indicate that the emodin-loaded nanofiber wound dressing can provide a potential treatment strategy for skin cancer postoperative management. Full article

Biphasic in vitro dissolution testing is an attractive approach to reflect on the interplay between drug dissolution and absorption for predicting the bioperformance of drug products. The purpose of this study was to investigate the in vivo relevance of a biphasic dissolution test for the immediate release (IR) formulations of a Biopharmaceutics Classification System (BCS) Class II drug, lamotrigine (LTG). The biphasic dissolution test was performed using USP apparatus II with the dual paddle modification. A level A in vitro-in vivo correlation (IVIVC) was constructed between the in vitro partition into the octanol and absorption data of the reference product. A good relation between in vitro data and absorption was obtained (r² = 0.881). The one-compartment open model was introduced to predict the human plasma profiles of the test product. The generic product was found to be bioequivalent to the original product in terms of 80–125% bioequivalence (BE) criteria (85.9–107% for the area under the plasma concentration curve (AUC) and 82.7–97.6% for the peak plasma concentration (C_max) with a 90% confidence interval (CI)). Overall, it was revealed that the biphasic dissolution test offers a promising ability to estimate the in vivo performance of IR formulations of LTG, providing considerable time and cost savings in the development of generic drug products. Full article

Coupling biorelevant in vitro dissolution with in silico physiological-based pharmacokinetic (PBPK) tools represents a promising method to describe and predict the in vivo performance of drug candidates in formulation development including non-passive transport, prodrug activation, and first-pass metabolism. The objective of the present study was to assess the predictability of human pharmacokinetics by using biphasic dissolution results obtained with the previously established BiPHa+ assay and PBPK tools. For six commercial drug products, formulated by different enabling technologies, the respective organic partitioning profiles were processed with two PBPK in silico modeling tools, namely PK-Sim and GastroPlus^®, similar to extended-release dissolution profiles. Thus, a mechanistic dissolution/precipitation model of the assessed drug products was not required. The developed elimination/distribution models were used to simulate the pharmacokinetics of the evaluated drug products and compared with available human data. In essence, an in vitro to in vivo extrapolation (IVIVE) was successfully developed. Organic partitioning profiles obtained from the BiPHa+ dissolution analysis enabled highly accurate predictions of the pharmacokinetic behavior of the investigated drug products. In addition, PBPK models of (pro-)drugs with pronounced first-pass metabolism enabled adjustment of the solely passive diffusion predicting organic partitioning profiles, and increased prediction accuracy further. Full article

Sangelose^® (SGL) is a novel hydroxypropyl methylcellulose (HPMC) derivative that has been hydrophobically modified. Due to its high viscosity, SGL has the potential as a gel-forming and release-rate-controlled material for application in swellable and floating gastroretentive drug delivery systems (sfGRDDS). The aim of this study was to develop ciprofloxacin (CIP)-loaded sfGRDDS tablets comprised of SGL and HPMC in order to extend CIP exposure in the body and achieve optimal antibiotic treatment regimes. Results illustrated that SGL-HPMC-based sfGRDDS could swell to a diameter above 11 mm and showed a short floating lag time (<4 s) and long total floating time (>24 h) to prevent gastric emptying. In dissolution studies, CIP-loaded SGL-HPMC sfGRDDS demonstrated a specific biphasic release effect. Among the formulations, the SGL/type-K HPMC 15,000 cps (HPMC 15K) (50:50) group exhibited typical biphasic release profiles, with F4-CIP and F10-CIP individually releasing 72.36% and 64.14% CIP within 2 h dissolution, and sustaining release to 12 h. In pharmacokinetic studies, the SGL-HPMC-based sfGRDDS demonstrated higher C_max (1.56–1.73 fold) and shorter T_max (0.67 fold) than HPMC-based sfGRDDS. Furthermore, SGL 90L in GRDDS indicated an excellent biphasic release effect and a maximum elevation of relative bioavailability (3.87 fold). This study successfully combined SGL and HPMC to manufacture sfGRDDS that retain CIP in the stomach for an optimal duration while improving its pharmacokinetic characteristics. It was concluded that the SGL-HPMC-based sfGRDDS is a promising biphasic antibiotic delivery system that can both rapidly achieve the therapeutic antibiotic concentration and maintain the plasma antibiotic concentration for an extended period to maximize antibiotic exposure in the body. Full article

A variety of in vitro dissolution and gastrointestinal transfer models have been developed aiming to predict drug supersaturation and precipitation. Further, biphasic, one-vessel in vitro systems are increasingly applied to simulate drug absorption in vitro. However, to date, there is a lack of combining the two approaches. Therefore, the first aim of this study was to develop a dissolution-transfer-partitioning system (DTPS) and, secondly, to assess its biopredictive power. In the DTPS, simulated gastric and intestinal dissolution vessels are connected via a peristaltic pump. An organic layer is added on top of the intestinal phase, serving as an absorptive compartment. The predictive power of the novel DTPS was assessed to a classical USP II transfer model using a BCS class II weak base with poor aqueous solubility, MSC-A. The classical USP II transfer model overestimated simulated intestinal drug precipitation, especially at higher doses. By applying the DTPS, a clearly improved estimation of drug supersaturation and precipitation and an accurate prediction of the in vivo dose linearity of MSC-A were observed. The DTPS provides a useful tool taking both dissolution and absorption into account. This advanced in vitro tool offers the advantage of streamlining the development process of challenging compounds. Full article

Biowastes from agriculture, sewage, household wastes, and industries comprise promising resources to produce biomaterials while reducing adverse environmental effects. This study focused on utilising waste-derived materials (i.e., eggshells as a calcium source, struvite as a phosphate source, and CH₃COOH as dissolution media) to produce value-added products (i.e., calcium phosphates (CaPs) derived from biomaterials) using a continuous flow hydrothermal synthesis route. The prepared materials were characterised via XRD, FEG-SEM, EDX, FTIR, and TEM analysis. Magnesium whitlockite (Mg-WH) and hydroxyapatite (HA) were produced by single-phase or biphasic CaPs by reacting struvite with either calcium nitrate tetrahydrate or an eggshell solution at 200 °C and 350 °C. Rhombohedral-shaped Mg-WH (23–720 nm) along with tube (50–290 nm diameter, 20–71 nm thickness) and/or ellipsoidal morphologies of HA (273–522 nm width) were observed at 350 °C using HNO₃ or CH₃COOH to prepare the eggshell and struvite solutions, and NH₄OH was used as the pH buffer. The Ca/P (atomic%) ratios obtained ranged between 1.3 and 1.7, indicating the formation of Mg-WH and HA. This study showed that eggshells and struvite usage, along with CH₃COOH, are promising resources as potential sustainable precursors and dissolution media, respectively, to produce CaPs with varying morphologies. Full article

Bioceramic scaffolds, composed of a biphasic composite containing bioactive glass and hydroxyapatite, were prepared in this work to overcome the intrinsic limits of the two components taken separately (in particular, their specific reactivities and dissolution rates, which should be tunable as a function of the given clinical requirements). To mimic the biological environment and tune the different stages of cellular response, a coating with gelatin and chondroitin sulphate via Layer-by-Layer (LbL) assembly was presented and discussed. The resulting functionalized scaffolds were affected by the coating in terms of microstructure and porosity. In addition, the LbL coating significantly enhanced the seeded cell behaviour, with high adhesion, proliferation and osteogenic activity, as revealed by the alkaline phosphatase activity and overexpression of osteopontin and osteocalcin. Full article