Search Results (45)

(1) Background: Fixed-dose combination (FDC) improves patient convenience and therapeutic adherence by combining suitable drugs in a single dose form. This study examined the in vitro dissolution of an ibuprofen-loratadine FDC oral suspension to commercial reference formulations. (2) Methods: The FDC suspension (ibuprofen 200 mg/5 mL, loratadine 5 mg/5 mL) was tested against Fenbro 8 Plus and Lorid on USP Apparatus II at 50 rpm and 37 ± 0.5 °C. Dissolution testing was carried out in 900 mL of phosphate buffer (pH 7.2) for ibuprofen and 0.1 N HCl (pH 3.3) for loratadine. Quantification was performed using validated high-performance liquid chromatography linked with ultraviolet detector (HPLC-UV) procedures complying with the ICH Q2 (R²) guidelines. (3) Results: The linearity of the HPLC methods for ibuprofen and loratadine was (R² > 0.99), accuracy (99.6–100.18%), and precision (%RSD < 2). For both loratadine and ibuprofen, the FDC suspension’s Q₁₅, Q₃₀, T₅₀, T₉₀, and DE% values nearly matched those of the commercial products. Over 95% of both drugs were released within 60 min. The dissolution equivalence between the FDC and the reference formulations was demonstrated by the calculated similarity (f₂) and difference (f₁) factors, which were f₁ = 3 and f₂ = 70 for ibuprofen, and f₁ = 4 and f₂ = 64 for loratadine. (4) Conclusions: The FDC suspension of ibuprofen and loratadine showed dissolving behavior comparable to commercial formulations, confirming its applicability for the practical and efficient treatment of allergy symptoms and inflammatory pain. Full article

Introduction: Levodopa (LD) is the most efficacious antiparkinsonian drug. However, long-term conventional LD treatment of Parkinson’s disease (PD) is frequently associated with motor complications. This can be attributed to pulsatile dopaminergic stimulation given the short LD half-life of conventional dosage forms. Tablets capable of delivering more stable and sustained dopaminergic stimulation would better mimic the brain’s natural dopamine activity. Methods: In this study, 3D screen printing technology was used to manufacture oral dosage forms characterized by the sequential release of Carbidopa and Levodopa. This was achieved by separating the two compounds into different compartments within the same dosage form, which were arranged (LXM.5-1) or formulated (LXM.5-2) in a specific way. Both novel dosage forms were compared to conventional immediate release forms such as Sinemet^®. The physicochemical properties of the resulting tablets, LXM.5-1 and LXM.5-2, were assessed in accordance with the USP. Their pharmacokinetic profiles were defined in pigs. Results: The physicochemical properties of LXM.5-1 and LXM.5-2 complied with regulatory requirements. Dissolution studies revealed sequential CD and LD release for both novel dosage forms. They differed regarding the interval between CD and LD release which was shorter for LXM.5-1. PK studies demonstrated that both novel dosage forms exhibited higher LD bioavailability in comparison to Sinemet^®, which was 211.36% and 383.64% for LXM.5-1 and LXM.5-2, respectively. Furthermore, blood levels were more stable and sustained, particularly for LXM.5-2. Conclusions: We conclude that 3D screen-printed LXM.5-1 and LXM.5-2 and variations thereof have the potential to transform the pharmacotherapy of Parkinson’s disease. Full article

Carbon Capture and Storage (CCS) is a critical strategy for reducing CO₂ emissions from hard-to-abate sectors. Reliable and efficient reservoir simulation tools are essential for supporting the safe and effective deployment of CCS projects. This study presents a twofold contribution to CCS modeling in saline aquifers: (1) the validation of the Black Oil Model (BoM) as a computationally efficient alternative to compositional simulators, and (2) a systematic assessment of the impact of grid resolution on plume prediction accuracy. The BoM was benchmarked against three commercial compositional simulators—Eclipse E300, CMG-GEM, and TNavigator. The comparison focused on key aspects of CO₂ storage operations, including plume evolution to assess containment and storage security, as well as injection safety and efficiency through pressure and saturation profile analysis, evaluated across both the injection and the post-closure monitoring phases. The BoM successfully reproduced plume extent and CO₂ saturation distributions, with mean deviations of 3% during injection, 5% during post-closure, and an overall average of 4% across the entire project duration. Additionally, simulation times were reduced by a factor of four compared to compositional models. These results confirm the BoM’s practical utility as a robust and efficient tool for CO₂ storage simulation. In parallel, the study investigated the influence of vertical and lateral grid resolutions/coarsening on the accuracy of CO₂ modeling. Seven models were developed and evaluated using a hybrid qualitative–quantitative framework, consistent with the BoM validation methodology. Vertical resolution was found to be particularly critical during the monitoring phase. While a 5 m resolution proved adequate during injection, deviations in plume shape and magnitude during post-injection increased to an average of 15% compared to a fine 2 m vertical resolution model, highlighting the necessity of fine vertical discretization (≤2 m) to capture gravity-driven plume dynamics during the monitoring phase. Conversely, lateral grid resolution had a stronger effect during the injection phase. A lateral cell size of 150 m was required for accurate plume prediction, with 200 m remaining moderately acceptable for early-phase assessment and prospect ranking, whereas coarser lateral grids led to significant underestimation of plume spread and dissolution extent. These findings demonstrate that the BoM, when combined with informed grid resolution strategies, enables accurate and computationally efficient simulation of CO₂ storage in saline aquifers. The study provides practical guidelines for fluid model selection and spatial discretization, offering critical input to subsurface experts involved in CCS project development, monitoring design, and regulatory compliance. Full article

Background/Objectives: Rivaroxaban, an oral anticoagulant, shows poor aqueous solubility, posing significant challenges to its bioavailability and therapeutic efficiency. The present study investigates the improvement of rivaroxaban’s solubility through the formation of different inclusion complexes with three cyclodextrin derivatives, such as β-cyclodextrin (β-CD), methyl-β-cyclodextrin (Me-β-CD), and hydroxypropyl-β-cyclodextrin (HP-β-CD) prepared by lyophilization in order to stabilize the complexes and improve dissolution characteristics of rivaroxaban. Methods: The physicochemical properties of the individual compounds and the three lyophilized complexes were analysed using Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), X-ray diffraction (XRD), and thermogravimetric analysis (TGA). Results: FTIR spectra confirmed the formation of non-covalent interactions between rivaroxaban and the cyclodextrins, suggesting successful encapsulation into cyclodextrin cavity. SEM images revealed a significant morphological transformation from the crystalline structure of pure rivaroxaban and cyclodextrins morphologies to a more porous and amorphous matrix in all lyophilized complexes. XRD patterns indicated a noticeable reduction in drug crystallinity, supporting enhanced potential of the drug solubility. TGA analysis demonstrated improved thermal stability in the inclusion complexes compared to the individual drug and cyclodextrins. Pharmacotechnical evaluation revealed that the obtained formulations (by comparison with physical mixtures formulations) possessed favorable bulk and tapped density values, suitable compressibility index, and good flow properties, making all suitable for direct compression into solid dosage forms. Conclusions: The improved cyclodextrins formulation characteristics, combined with enhanced dissolution profiles of rivaroxaban comparable to commercial Xarelto^® 10 mg, highlight the potential of both cyclodextrin inclusion and lyophilization technique as synergistic strategies for enhancing the solubility and drug release of rivaroxaban. Full article

Background/Objectives: Inhaler devices have been developed for the effective delivery of inhaled medications used in the treatment of pulmonary diseases. However, differing operating procedures across the devices can lead to user errors and reduce treatment efficacy, especially when patients use multiple devices simultaneously. To address this, we developed a novel dry powder inhaler (DPI), combining fluticasone propionate (FP), salmeterol xinafoate (SX), and tiotropium bromide (TB) into a single device designed for bioequivalent delivery compared to existing commercial products in an animal model. Methods: The micronized FP/SX/TB-loaded capsule was prepared by sieving, blending, and filling capsules. Capsule suitability of the drugs was investigated from the comparison of the stability of drugs within various capsule formulations to that of commercial products. The particle size of the drugs was adjusted using spiral air jet milling, and the ratio of lactose hydrate carriers was optimized by comparing the aerodynamic particle size distribution (APSD) with that of commercial products. To investigate the bioequivalence of micronized FP/SX/TB-loaded DPI to commercial products, the dissolution profile of FP/SX/TB particles and pharmacokinetics in rats were evaluated and compared to commercial products. Results: Capsules with hydroxypropyl methylcellulose (HPMC) without a gelling agent showed superior stability of the drugs compared to commercial products. The deposition pattern was influenced by the particle size of the drugs, and fine particle mass exhibited a significant correlation with the amount of fine carrier. Micronized FP/SX/TB-loaded DPI gave a similar APSD and dissolution profile compared to the commercial products and showed dose uniformity by the DPI device. Furthermore, micronized FP/SX/TB-loaded DPI exhibited bioequivalence to commercial products, as evidenced by no significant differences in pharmacokinetic parameters following intratracheal administration in rats. Conclusions: A novel triple-combination DPI containing FP/SX/TB was successfully developed, demonstrating comparable pharmacological performance to commercial products. Optimized FP/SX/TB-loaded DPI with HPMC capsule achieved bioequivalence in rat studies, suggesting its potential for improved patient compliance and therapeutic outcomes. This novel single-device DPI offers a promising alternative for triple therapy in pulmonary diseases. Full article

Background/Objectives: A sustained-release formulation of fenofibrate while enhancing drug dissolution with minimal food effect is critical for maximizing the therapeutic benefits of fenofibrate. Therefore, this study aimed to develop an effective solid dispersion formulation of fenofibrate for simultaneous enhancement in the extent and duration of drug exposure. Methods: Fenofibrate-loaded solid dispersions (FNSDs) were prepared using poloxamer 407 and Eudragit^® RSPO at varied ratios via solvent evaporation. In vitro/in vivo characteristics of FNSDs were examined in comparison with untreated drugs. Results: Based on dissolution profiles of FNSDs in aqueous media, the weight ratio of fenofibrate: poloxamer 407: Eudragit^® RSPO at 1:1:4 (FNSD2) was selected as the optimal composition for achieving sustained drug release while maximizing the drug dissolution. The enhanced and sustained drug release of FNSD2 was also confirmed in a buffer transition system mimicking the pH change in the gastrointestinal tract. FNSD2 achieved approximately 66% drug release over 12 h, while pure drug exhibited only 12%. Furthermore, FNSD2 maintained similar release rates under fed and fasted conditions, while the entire drug dissolution slightly increased in the fed state. Structural analysis by x-ray diffraction showed that fenofibrate remained crystalline in FNSD2. Pharmacokinetic studies in rats revealed that orally administered FNSD2 significantly improved the extent and duration of systemic drug exposure. Compared to pure drugs, the FNSD2 formulation increased the oral bioavailability of fenofibrate by 22 folds with the delayed T_max of 4 h in rats. Conclusion: FNSD2 formulation is effective in improving the extent and duration of drug exposure simultaneously. Full article

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. Full article

Mesoporous silica particles (MSPs) have been investigated as potential carriers to increase the apparent solubility and dissolution rate of poorly water-soluble drugs by physically stabilising the amorphous nature of the loaded drug. In preparing such systems, it is recognized that the loading method has a critical impact on the physical state and performance of the drug. To date, there has been very limited investigation into the use of electrospraying for loading drugs into mesoporous silica. In this study, we further explore the use of this approach, in particular as a means of producing amorphous and high drug-loaded MSPs; the study includes an investigation of the effect of drug loading and MSP concentration on the formulation performance and process. A comparison with rotary evaporation, a more widely utilised loading technique, was conducted to assess the relative effectiveness of electrospraying. The physical state of the drug in the formulations was assessed using powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC). The drug release profiles were determined by a comparative in vitro drug release test. Electrospraying successfully produced formulations containing amorphous drug even at a high drug loading. In contrast, while itraconazole was present in amorphous form at the lower drug-loaded formulations produced by rotary evaporation, the drug was in the crystalline state at the higher loadings. The percentage of drug released was enhanced up to ten times compared to that of pure itraconazole for all the formulations apart from the highest loaded (crystalline) formulation prepared by rotary evaporation. Supersaturation for at least six hours was maintained by the formulations loaded with up to 30 mg/mL itraconazole produced by electrospraying. Overall, the results of this study demonstrate that electrospraying is capable of producing amorphous drug-loaded MSPs at high loadings, with associated favourable release characteristics. A comparison with the standard rotary evaporation approach indicates that electrospraying may be more effective for the production of higher loadings of amorphous material. Full article

Background: Pazopanib hydrochloride (PZB) is a protein kinase inhibitor approved by the United States Food and Drug Administration and European agencies for the treatment of renal cell carcinoma and other renal malignancies. However, it exhibits poor aqueous solubility and inconsistent oral drug absorption. In this regard, the current research work entails the development and evaluation of the extrudates of pazopanib hydrochloride by the hot-melt extrusion (HME) technique for solubility enhancement and augmenting oral bioavailability. Results: Solid dispersion of the drug was prepared using polymers such as Kollidon VA64, hydroxypropylmethylcellulose (HPMC), Eudragit EPO, and Affinisol 15LV in a 1:2 ratio by the HME process through a lab-scale 18 mm extruder. Systematic optimization of the formulation variables was carried out with the help of custom screening design (JMP Software by SAS, Version 14.0) to study the impact of polymer type and plasticizer level on the quality of extrudate processability by measuring the torque value, appearance, and disintegration time as the responses. The polymer blends containing Kollidon VA64 and Affinisol 15LV resulted in respective clear transparent extrudates, while Eudragit EPO and HPMC extrudates were found to be opaque white and brownish, respectively. Furthermore, evaluation of the impact of process parameters such as screw rpm and barrel temperature was measured using a definitive screening design on the extrude appearance, torque, disintegration time, and dissolution profile. Based on the statistical outcomes, it can be concluded that barrel temperature has a significant impact on torque, disintegration time, and dissolution at 30 min, while screw speed has an insignificant impact on the response variables. Affinisol extrudates showed less moisture uptake and faster dissolution in comparison to Kollidon VA64 extrudates. Affinisol extrudates were evaluated for polymorphic stability up to a 3-month accelerated condition and found no recrystallization. PZB–Extrudates using the Affinisol polymer (Test formulation A) revealed significantly higher bioavailability (AUC) in comparison to the free Pazopanib drug and marketed formulation. Full article

Background and Objectives: The enteric form of omeprazole is one of the most commonly prescribed medications. Similarly to Europe, Kazakhstan relies on the localization of pharmaceutical drug production as one of its primary strategies to ensure that its population has access to affordable and good-quality medicines. This study comprehensively describes the technologically available development of bioequivalent delayed-release omeprazole. Materials and Methods: Various regimes and technological parameters were tested on laboratory- and production-scale equipment to establish a technical process where a functional and gastro-protective layer is essential. According to the ICH guidance on stability testing and Kazakhstan local rules, stability studies were conducted under conditions appropriate for climate zone II. The comparison of the rate and extent of absorption with subsequent assessment of the bioequivalence of the generic and reference drugs after a single dose of each drug at a dose of 40 mg was performed. Results: The quantitative and qualitative composition and technology of producing a new generic enteric form of omeprazole in capsules were developed and implemented at the manufacturing site of solid forms. Dissolution profiles in media with pH 1.2 and 6.8 were proven. During the accelerated six-month and long-term twelve-month studies, the developed formulation in both packaging materials at each control point passed the average weight and mass uniformity test, dissolution test, acid-resistance stage test, buffer stage test, impurity assay, and microbiological purity test and met all the specification criteria. A bioequivalence study in 24 healthy volunteers compared against the innovative drug showed the bioequivalency of the new generic system. The obtained values from the test and reference products were 1321 ± 249.0 ng/mL and 1274 ± 233 ng/mL for C_max, 4521 ± 841 ng·h /mL and 4371 ± 695 ng·h /mL for AUC_0-t, and 4636 ± 814 ng·h /mL and 4502 ± 640 ng·h /mL for AUC_0-∞. Conclusions: Using affordable technologies, a bioequivalent generic delayed-release formulation of 20 and 40 mg omeprazole has been developed. Full article

In this work, polyvinylpyrrolidone (PVP)- and β-cyclodextrin (β-CD)-based composite powders containing curcumin (CURC) were obtained through the supercritical antisolvent (SAS) technique. Pressure, total concentration of CURC/carrier in dimethylsulfoxide, and CURC/carrier ratio effects on the morphology and size of the precipitated powders were investigated. Using PVP as the carrier, spherical particles with a mean diameter of 1.72 μm were obtained at 12.0 MPa, 20 mg/mL, and a CURC/PVP molar ratio equal to 1/2 mol/mol; using β-CD as the carrier, the optimal operating conditions were 9.0 MPa and 200 mg/mL; well-defined micrometric particles with mean diameters equal to 2.98 and 3.69 μm were obtained at molar ratios of 1/2 and 1/1 mol/mol, respectively. FT-IR spectra of CURC/ β-CD inclusion complexes and coprecipitated CURC/PVP powders revealed the presence of some peaks of the active compounds. The stoichiometry of the complexes evaluated through the Job method revealed that β-CD formed inclusion complexes with CURC at a molar ratio equal to 1/1. Dissolution profiles revealed that in comparison with the curve of the pure ingredient, the SAS-processed powders obtained using both PVP and β-CD have an improved release rate. Full article

Itraconazole (ITZ) is a broad-spectrum antifungal for superficial subcutaneous and systemic fungal infections. This study aimed to enhance the antifungal activity of ITZ using surfactin A (SA), a cyclic lipopeptide produced by the SA-producing Bacillus strain NH-100, possessing strong antifungal activity. SA was extracted, and ITZ-loaded SA micelles formulations were prepared via a single-pot rinsing method and characterized by particle size, zeta potential, and infrared spectroscopy. In vitro dissolution at pH 1.2, as well as hemolysis studies, was also carried out. The fabricated formulations were stable and non-spherical in shape, with an average size of about 179 nm, and FTIR spectra depicted no chemical interaction among formulation components. ITZ-loaded micelles showed decreased hemolysis activity in comparison to pure ITZ. The drug released followed the Korsmeyer–Peppas model, having R² 0.98 with the diffusion release mechanism. In an acidic buffer, drug release of all prepared formulations was in the range of 73–89% in 2 h. The molecular simulation showed the outstanding binding and stability profile of the ITZ-SA complex. The aromatic ring of the ITZ mediates a π-alkyl contact with a side chain in the SA. It can be concluded that ITZ-loaded micelles, owing to significant enhanced antifungal activity up to 6-fold due to the synergistic effect of SA, can be a promising drug delivery platform for delivery of poorly soluble ITZ. Full article

Eu-doped periodic mesoporous organosilicate (PMO) films with terminal methyl and ethylene bridging groups have been synthesized using sol-gel technology and spin-coating, employing evaporation-induced self-assembly (EISA), on silicon wafers. Eu doping is achieved by the dissolution of Eu(NO₃)₃·6H₂O in the precursor solution. The deposited films are characterized using Fourier transform infrared (FTIR) spectroscopy, ellipsometric porosimetry (EP), X-ray photoelectron spectroscopy (XPS) and photoluminescence spectroscopy. It is observed that Eu doping reduces the concentration of terminal methyl groups, makes the films more hydrophilic and reduces the pore size and open porosity. The reduction reaction Eu³⁺ → Eu²⁺ occurs in the pores of organosilicate glass (OSG) films, which was confirmed by the depth profiling XPS. Eu³⁺ was still present on the top surface of the films. The presence of Eu³⁺ and Eu²⁺ gives luminescence emission in the range of 600–630 nm (Eu³⁺) and 290–400 nm (Eu²⁺). The Eu²⁺/Eu³⁺ concentrations ratio depends on CH₃ groups concentration in the films. The concentration of Eu²⁺ ions in the pores can be reduced by exposure to inductively coupled (ICP) oxygen plasma. The observed shift in the luminescence spectra towards the UV region, in comparison to previously reported Eu-doped organosilicate films, can be attributed to the energy transfer occurring between the host material and Eu²⁺ ions. Full article

The aim of the study was the preparation and comparison of two types of orodispersible gel films (ODF) by the solvent casting method. Natural polymers: sodium alginate (ALG) or hydroxypropyl methylcellulose (HPMC) were used as the gel film formers, and Kollidon or microcrystalline cellulose was used as the disintegrant. Meloxicam (MLX), the drug used to treat rheumatic diseases for children and adults, was proposed as the active pharmaceutical ingredient (API). The influence of the polymer and disintegrant on the properties of ODF was investigated. The evaluation of prepared gel films was based on appearance description, mass uniformity measurement, disintegration time, API content, film wettability, and water content. Also, the dissolution test was prepared in a basket apparatus using artificial salvia (pH = 6.8) as the medium. The obtained API release profiles were analyzed for the similarity factors (f₂) with the DDSolver software. The results showed that independently of the polymer or disintegrant, using the solvent casting method, gel films have a similar appearance and active substance content close to the theoretical value and water content of less than 10%. Only the type of polymer influences the release profiles of MLX. However, the disintegration time was longer than 30 s, which makes the films non-fast-dissolving drug delivery systems. This means that for the ODF system, further evaluation is required, and some changes in the composition of the film have to be done. Full article

The use of the USP IV apparatus (flow-through cell) has gained acceptance in recent years due to its versatility and ability to discriminate due to its hydrodynamic conditions. Therefore, the objective of the present study was to develop a discriminative dissolution method in the USP IV apparatus using the open-loop configuration, as well as to propose a method to compare non-cumulative dissolution profiles obtained in the open-loop configuration considering kinetic parameters and validate its predictive power through its comparison with independent and dependent methods using five commercial immediate-release tablet drugs (one reference drug and four generic drugs) of metoprolol tartrate as a model drug. The comparison of the non-accumulated dissolution profiles consisted of determining the geometric ratio of C_max, AUC₀^∞, AUC₀^Cmax, and T_max (kinetic parameters) of the generic/reference drugs, whereby generic drugs “C” and “D” presented the highest probability of similarity since their 90% confidence intervals were included, or they were very close to the acceptance interval (80.00–125.00%). These results were consistent with the f₂, bootstrap f_2, and dissolution efficiency approaches (independent models). In conclusion, the proposed comparison method can be an important tool to establish similarity in dissolution profiles and to facilitate the development/selection of new formulations and positively ensure bioequivalence in clinical studies. Full article