Search Results (519)

Cytisine is a plant-derived quinolizidine alkaloid found, among other sources, in the seeds of the common laburnum (Laburnum anagyroides). It has properties that enable it to act as a partial agonist of brain nicotinic α4β2 receptors, which play a key role in the development and maintenance of nicotine addiction. Clinical studies have shown that cytisine is a more effective smoking cessation aid than nicotine replacement therapy and at least as effective as varenicline in treating tobacco cigarette addiction. It may also be an effective agent in treating addiction to electronic cigarettes. Cytisine is also significantly cheaper than other anti-nicotine medications. This is of great importance for the population of smokers in developing countries, who cannot afford anti-nicotine treatment. In recent years, the role of cytisine in the pharmacotherapy of nicotine addiction worldwide has increased significantly. This drug is becoming available in an increasing number of countries, and in 2025 the World Health Organization (WHO) added cytisine to the list of essential medicines. The need for further development of the drug poses additional challenges for scientists, including the creation of new pharmaceutical forms, optimization of dosing regimens, and expansion of indications to include the treatment of nicotine addiction supplied into the body in forms other than traditional tobacco products. This review describes the use of cytisine in the treatment of nicotine addiction, the drug’s mechanism of action, pharmacokinetics, efficacy, safety of use, and the available pharmaceutical preparations. It also presents research directions on cytisine related to the development of innovative pharmaceutical products, new dosing regimens, and new indications associated with the treatment of addiction to various nicotine-containing products. Conclusions indicate that cytisine has a difficult dosing regimen, which is why patients do not adhere to it, limiting the effectiveness of the therapy. This necessitates optimizing the dosage of existing capsules and tablets or introducing, for example, new extended-release forms of the drug containing cytisine. Full article

Background: The dissolution of oral solid dosage forms is a key determinant of drug bioavailability, yet traditional testing methods do not capture the real-time surface dynamics of drug release. This study introduces a novel framework combining surface dissolution imaging (SDi2) with an interpretable, dual-wavelength convolutional neural network (CNN) to predict and understand dissolution behavior. Methods: Eight tablet formulations containing acetylsalicylic acid, sodium salicylate, or salicylamide, combined with either lactose or methylcellulose, were analyzed under two distinct, compendial conditions (pH 1.2 and pH 6.8). Results: Our final CNN model, which synergistically processes spectral images (280 nm for API release and 520 nm for structural changes), temporal data, and formulation composition, accurately predicted dissolution profiles, achieving a coefficient of determination of 0.89 and a root mean square error (RMSE) of 11.57. To overcome the “black-box” nature of deep learning, we employed Gradient-weighted Class Activation Mapping (Grad-CAM) to interpret the model’s predictions. The analysis revealed that the model focused on tablet edges at 280 nm, consistent with surface dissolution, and on bulk regions at 520 nm, reflecting structural changes including erosion and gel-layer growth. Conclusions: These findings suggest that integrating real-time imaging with explainable AI methods can support better understanding of dissolution processes in pharmaceutical formulation development. Full article

Since differential scanning calorimetry (DSC) is an excellent method for studying phase transformations in the solid state, the purpose of this study was to assess the suitability of DSC as a method for detecting physicochemical transformations occurring in solid drug products during storage, extending also beyond their expiration date. Based on the DSC measurements of 34 commercial drug products, they were divided into three groups characterized by the fact that the DSC curves show: (I) as dominant endothermic peaks reflecting active pharmaceutical ingredients (APIs) melting, with no additional peaks from excipients, (II) in addition to the peaks reflecting APIs melting, additional peaks related to the excipients, and (III) two peaks characteristic of lactose monohydrate dehydration and melting. Analysis of the temperature ranges and the shape of the DSC peaks showed no significant differences between the six series of measurements performed between 2011 and 2022, suggesting that physicochemical changes in drug products could not be detected during storage. Only the use of principal component analysis (PCA) made it possible to separate the DSC curves obtained during long-term storage of drug products. This allows DSC to be used to detect the first signs of deterioration, but only for drug formulations in group one. Of the drug products in groups two and three, this is only possible for 14 products. It follows that the suitability of DSC for identifying physicochemical changes in products stored for long periods of time is affected by the API content and complex composition of the tablet matrix. Full article

Background/Objectives: Beeswax, a complex natural secretion primarily derived from Apis mellifera and Apis cerana, has evolved from an ancient remedy into a multifunctional excipient and bioactive material in modern pharmaceutical sciences. This review evaluates its physicochemical properties, pharmaceutical applications, and emerging biomedical potential, while addressing current quality and regulatory challenges. Methods: A narrative review was conducted by analyzing literature on the chemical composition, functional properties, conventional uses, advanced drug delivery applications, pharmacological activities, and quality control of beeswax, emphasizing structural characteristics, formulation roles, and integration into innovative delivery technologies. Results: Beeswax is a lipid-based matrix composed of over 300 constituents, including wax esters, hydrocarbons, and free fatty acids, conferring thermoplasticity, biocompatibility, and structural stability. Traditionally, it functions as a stiffening agent, viscosity modifier, and emulsion stabilizer in topical formulations, forming an occlusive barrier that enhances skin hydration. In advanced systems, it serves as a solid lipid matrix in nanostructured lipid carriers (NLCs), microspheres, and 3D-printed tablets, enabling controlled drug release and improved bioavailability of lipophilic compounds. It also exhibits antimicrobial, anti-inflammatory, and wound-healing activities, while beeswax-derived policosanols show potential cardiovascular and gastroprotective benefits. However, concerns regarding paraffin adulteration and pesticide contamination highlight the need for stringent analytical and regulatory oversight. Conclusions: With rigorous quality control and sustainable sourcing, beeswax remains a versatile, eco-friendly material bridging traditional medicine and advanced pharmaceutical innovation. Full article

Background/Objectives: Iron is a key micronutrient for the proper growth and development of the organism. The aim of this study was to evaluate the impact of diet type, the chemical form of iron, and the formulation of the pharmaceutical preparation on its relative bioaccessibility from selected dietary supplements and medicinal products. Methods: The research was conducted using a two-stage in vitro digestion model, simulating the physiological processes occurring in the human digestive system and ICP-OES determination of iron. The analytical model used in the study involved homogenates of whole-day dietary rations (basic, standard, and high-residue diets) with the addition of selected dietary supplements or medicinal products. It was demonstrated that iron bioaccessibility was strictly determined by dietary composition and the chemical form of the preparation. Results: In the studies conducted without external supplementation, the highest iron bioaccessibility was observed in the basic diet model (7.96%), and the lowest in the standard diet (4.63%). The highest bioaccessibility value was determined for iron sulfate registered as medicine (12.58%), whereas the lowest was iron lactate (5.25%). The extended-release tablets observed the highest bioaccessibility (19.31%). Conclusions: It was proven that the developed in vitro digestion model may serve as an effective tool for the preliminary assessment of iron bioaccessibility, enabling the optimization of supplementation without ethical barriers. Full article

Background: H007 is a novel selective AMP-activated protein kinase (AMPK) activator with demonstrated efficacy against hyperlipidemia; however, its oral bioavailability is limited by poor solubility and low intestinal permeability. This study aimed to develop a self-microemulsifying drug delivery system (SMEDDS) incorporating a H007–phospholipid complex (H007-PC) to improve both solubility and intestinal permeability. Methods: H007-PC-SME was prepared by integrating phospholipid complexes into an SMEDDS formulation. The formulation was optimized on the basis of emulsification efficiency, droplet size, and zeta potential, and was then evaluated for stability, in vitro drug release, and cellular uptake. Different H007 formulations were orally administered to golden hamsters to assess bioavailability, and a chylomicron flow blockade hamster model was used to evaluate lymphatic transport. Results: The optimized H007-PC-SME showed good stability, rapid self-emulsification, and improved drug solubility. Relative to ordinary H007 tablets, the relative bioavailability of H007-SME and H007-PC-SME was 376.65% and 464.62%, respectively, when calculated from M1 exposure, and 314.01% and 463.55%, respectively, when calculated from MP exposure. When evaluated in a cycloheximide model, H007-SME and H007-PC-SME increased the lymphatic transport fraction of M1 from approximately 0% to 22% and 54%, and that of MP from approximately 1% to 28% and 52% compared with ordinary H007 tablets. Conclusion: H007-PC-SME combines stable phospholipid complex formation with strong self-emulsification performance and effective drug dissolution. By overcoming the intrinsic limitations of the H007 active pharmaceutical ingredient and ordinary H007 tablets, this formulation improves membrane permeability and lymphatic transport, thereby enhancing oral bioavailability and therapeutic potential. The formulation shows good stability and acceptable in vitro biocompatibility under the tested conditions. The preparation process is straightforward, reproducible, and suitable for further pharmaceutical development. Full article

Background/Objectives: Tablet development requires simultaneous optimization of multiple quality attributes under limited experimental budgets, yet formulation–property relationships are highly nonlinear in mixture systems. To support pre-formulation decision-making prior to extensive tablet prototyping, this study proposes an AI framework that organizes formulation and process data together with raw-material property records into a reusable database, and enriches conventional composition/process features with physically motivated mixture descriptors derived from raw-material properties and formulation/process settings. Methods: Mixture-level scalar descriptors are constructed by composition-weighted aggregation of material properties, and particle size distribution (PSD) is incorporated via a compact set of summary statistics computed from composition-weighted mixture PSDs. Three feature sets are compared: (i) Materials + Processes (MP), (ii) MP with scalar Descriptors (MPD), and (iii) MPD with PSD summaries (MPDD). Five target properties are modeled: hardness, disintegration time, flow function, cohesion, and thickness. We train and evaluate Random Forest, Extra Trees Regressor, Lasso, Partial Least Squares, Support Vector Regression, and a multi-branch neural network that processes the three feature blocks separately and concatenates them for prediction. For interpolation assessment, repeated Train/Dev/Test splitting (5:3:2) across multiple random seeds is used, and the effect of feature augmentation is quantified by paired RMSE improvements with bootstrap confidence intervals and paired Wilcoxon signed-rank tests. To assess robustness under practical formulation updates, rolling-origin time-series splits are employed and Applicability Domain indicators are computed to characterize out-of-distribution coverage. Results: Across interpolation evaluations, mixture-descriptor augmentation (MPD/MPDD) improves hardness and disintegration time in most settings, whereas gains for flow function are smaller and cohesion/thickness show mixed effects under limited sample sizes. Conclusions: Under extrapolation-oriented evaluation, the descriptors can improve hardness but may degrade disintegration-time prediction under covariate shift, emphasizing the need for careful descriptor selection and dimensionality control when deploying pre-formulation predictors. Full article

This study aimed to develop a 100 mg immediate-release (IR) tablet containing dasatinib monohydrate, a tyrosine kinase inhibitor, using a Quality by Design (QbD) framework at laboratory scale. The development strategy focused on systematic identification and control of critical process parameters (CPPs) affecting tablet quality during wet granulation. Preformulation studies were conducted to evaluate key physicochemical properties of the active pharmaceutical ingredient (API), including solubility, particle size distribution, and crystallinity, which may influence dissolution behavior. A risk assessment approach based on preliminary hazard analysis (PHA) and failure mode and effects analysis (FMEA) was applied to identify high-risk process variables. Based on the risk assessment results, chopper speed during wet granulation and compression force during tableting were identified as critical process parameters. These factors were further investigated using a Design of Experiments (DoE) approach based on Define Custom Design (DCD) and response surface methodology (RSM) to evaluate their effects on critical quality attributes (CQAs), including dissolution performance, disintegration time, and tablet friability. Response surface analysis established a design space in which chopper speed ranged from approximately 2300–2500 rpm and compression force ranged from 11 to 13 kN, ensuring consistent tablet quality within the investigated operating range. The optimized process conditions produced tablets that satisfied predefined quality targets. Comparative dissolution studies demonstrated dissolution profiles comparable to the reference product across pH 1.2, 4.0, and 6.8 media, with similarity factor (f₂) values ranging from 51.18 to 85.23. The experimentally established design space demonstrated reproducible in vitro performance and physicochemical stability under accelerated storage conditions. Overall, this study demonstrates the practical application of a QbD-based development strategy integrating risk assessment and response surface optimization to improve process understanding and manufacturing robustness in wet granulation-based tablet production. Full article

A robust and unified reversed-phase high-performance liquid chromatography (RP-HPLC) method was developed and validated for the simultaneous quantitative analysis of pitavastatin calcium and fenofibrate in dual-layer tablet formulations. Although individual analytical methods for each active pharmaceutical ingredient have been reported, a single analytical procedure applicable to both assay and dissolution testing of this fixed-dose combination has not been sufficiently established. In this study, a single RP-HPLC method was optimized to support both quality control purposes, thereby improving analytical efficiency and reducing method-related variability. Chromatographic separation was achieved using a C18 column (4.6 × 150 mm, 5 µm) under isocratic conditions, with a flow rate of 1.1 mL/min, an injection volume of 40 µL, and UV detection at 245 nm. The total run time was 10 min. The method was validated in accordance with ICH guideline Q2(R1) for system suitability, specificity, linearity and range, accuracy, precision (repeatability and intermediate precision), limits of detection and quantitation, and solution stability. Validation was conducted for both assay and dissolution samples using the same chromatographic conditions. The method demonstrated excellent linearity over the validated concentration ranges for both assay and dissolution analyses (r² ≥ 0.99). Accuracy and precision results satisfied the predefined acceptance criteria for assay (98.0–102.0%) and dissolution-related quantification (95.0–105%), with relative standard deviation values not exceeding 2.0%. The method showed adequate sensitivity, specificity, and solution stability, confirming its suitability for routine analysis. Application of the validated method to finished dual-layer tablets demonstrated reliable assay results and clearly distinguished the rapid dissolution of pitavastatin calcium from the delayed dissolution behavior of fenofibrate. Overall, the developed RP-HPLC method provides a validated analytical platform capable of supporting both assay and dissolution testing of pitavastatin–fenofibrate dual-layer tablets. Beyond routine validation, the proposed analytical framework demonstrates how a single chromatographic condition can support multiple quality attributes, offering an analytically integrated approach for supporting multiple quality attributes in complex combination drug products. Full article

Background/Objectives: The use of over-the-counter vitamin D₃ supplements has increased substantially in recent years. Compared with pharmaceuticals, dietary supplements are subject to less stringent regulatory oversight, raising concerns regarding labeling accuracy, consumer knowledge, and patient safety. This study aimed to assess public knowledge and preferences related to vitamin D₃ supplementation and to evaluate the content accuracy and short-term stability of commonly used products. Methods: A cross-sectional online survey containing 39 questions was conducted in Hungary between 1 May and 30 June 2024. Based on survey responses, the most frequently used vitamin D₃ supplements (five soft gel capsules and four tablets) were selected for laboratory analysis. Vitamin D₃ content was quantified using a validated high-performance liquid chromatography (HPLC) method with UV detection. Soft gel capsules were additionally exposed to natural daylight for one month to assess short-term photostability. Results: In total, 367 participants (mean age 31.0 ± 12.5 years) completed the survey, and only 3.5% answered correctly all knowledge-based questions. Six commonly reported supplement brands accounted for approximately 90% of responses. Measured vitamin D₃ content remained within the tolerance limit (−20% to +50%). Following sunlight exposure, three of four capsule products showed no substantial vitamin D₃ loss, while one exhibited a 14.7% decrease. Conclusions: Most analyzed vitamin D₃ supplements complied with labeled content claims, but substantial knowledge gaps were identified that may affect patient safety. The validated HPLC method supports pharmacovigilance-oriented quality monitoring of vitamin D₃ supplements and underscores the need for improved professional counseling. Full article

Objectives: The current study presents a sequential strategy for the development of directly compressible powder formulations relying on Design of Experiments (DoE) and Compactibility-Ejection stress plots. Methods: Compression analysis was used to evaluate the impact of changing the sort of microcrystalline cellulose (MCC), dicalcium phosphate (DCP), the diluent ratio, lubricant type, and the inclusion of an API from different suppliers. Results: The effect of DCP particle size on the ejection stress was efficiently mitigated in the placebo formulations by lubrication. However, the initial differentiation between sorts was highlighted at a smaller scale when the active pharmaceutical ingredient (API) was included in the formulation. For MCC, the tensile strength was positively correlated with the level of plasticity and tabletability capacity of different sorts. The particle size was a critical attribute for the API, influencing the detachment and ejection stress values. Fine particles (d50 = 30 µm) presented increasing stress values once the compression force rose, while for coarser particles (d50 = 50 µm) these effects were limited. Conclusions: Material-related variability must be understood to design products and processes with adequate performance. The proposed strategy enables early identification of critical material attributes, supporting rational formulation and supplier selection to ensure consistent quality during manufacturing. Full article

To address the problems of high labor intensity, high production cost, low efficiency, and unevenness in the manual seed dressing process of cut potatoes, as well as the poor quality and easy damage caused by the poor adaptability of existing seed dressing equipment, this study designs a drum-type seed dressing device for cut potatoes based on design principles of seed treatment machinery. A kinematic model of the seed dressing process was established, and the process was simulated using EDEM 2024 discrete element simulation software combined with ray tracing. Two indicators commonly used in the pharmaceutical industry were introduced to evaluate seed dressing uniformity: the inter-tablet variation coefficient (CoV_inter) and intra-tablet variation coefficient (CoV_intra). Through single-factor experiments and three-factor, five-level orthogonal rotational combination experiments, the influence of drum speed, spiral guide plate pitch, and feed rate on the seed dressing effect were explored, and the parameters were optimized. The results show that the optimal parameter combination is a drum speed of 32.84 r·min⁻¹, a spiral guide plate pitch of 682.64 mm, and a feed rate of 10.44 t·h⁻¹, at which CoV_inter was 6.33% and CoV_intra was 6.35%. Bench tests verified that the seed dressing pass rate reached 94.1% and the breakage rate was only 0.32% under this parameter combination, meeting the requirements for seed potato treatment in mechanized potato planting. These findings can facilitate the progress of potato-seed engineering and offer theoretical and technical support for the development of mechanized potato seed dressing equipment. Full article

Background/Objectives: 3D printing, particularly fused deposition modeling (FDM), is an emerging technology in pharmaceutical manufacturing, enabling the customization of dose or release rate to individual patient needs. However, finding the appropriate loading method to ensure the stability of the drug and achieve the targeted dose may be challenging. Furthermore, the drug utilization of most loading methods is poor, which results in considerable waste production and increased environmental burden. This study aimed to compare two post-printing drug-loading techniques: electronic syringe deposition and pan coating on FDM-printed polylactic acid (PLA) tablets. PLA is a biodegradable and biocompatible polymer that is widely used in this field due to its mechanical strength and regulatory approval. Methods: Tablets with honeycomb-shaped infill (30% and 60% infill densities) were fabricated using PLA filaments, followed by loading with a 15% paracetamol solution via either electronic syringe deposition or pan coating. The resulting tablets were assessed for drug content, weight variation, friability%, surface morphology (SEM), drug distribution (Raman mapping), solid-state characteristics (DSC and FTIR), and dissolution performance. Results: The results indicated that pan coating and electronic syringe deposition offered drug utilization up to 88% and 91.7%, respectively, which is superior to conventional soaking methods. Nevertheless, there is a significant difference in drug loading and release rate: pan coating yielded up to 10.14% drug loads and fast release (over 80% in 30 min), while electronic syringe deposition showed lower drug loading up to 4.8% and slower release (less than 80% within 60 min), which could be associated with better mechanical film integrity and higher precision. Both methods met USP standards with a weight loss of less than 1% and maintained the drug’s crystalline state and compatibility with PLA. Conclusions: FDM combined with controlled post-printing drug loading presents a rapid, cost-effective, and flexible novel approach for manufacturing personalized immediate-release tablets, with pan coating potentially being more suitable for commercial scalability and electronic syringe offering precise dosing for personalized therapies. Full article

Background/Objectives: We conducted this study to develop a generic amiodarone tablet pharmaceutically equivalent to the reference drug. This development is crucial for securing a stable supply chain for this orphan drug, which currently faces domestic market instability. Amiodarone, a national essential medicine, often experiences unstable supply due to its limited profitability. Methods: To secure this stable supply chain, we employed a factorial design, utilizing a Quality by Design (QbD) approach, to create the most suitable formulation. Initially, we observed a limitation where the formulation exhibited a flowability of 25% based on the Carr’s Index, which exceeded the target of 20%. To address this challenge, we incorporated lactose monohydrate during the pre-mixing stage rather than the post-mixing stage. Subsequently, we identified the binder content and the amount of granulation solvent as Critical Material Attributes (CMAs), and we performed a Design of Experiments (DoE). Result: Based on these investigations, we determined that the optimal prescription utilizes 5.71% povidone K25 and 40 mg/T of purified water. The final formulation successfully achieved an excellent flowability of 15.8%. Furthermore, this formulation showed a dissolution and bioequivalence PK profile equivalent to the reference drug in pH 1.2, 4.0, and 6.8 buffer solutions, each containing 1% Tween 80. Conclusions: Ultimately, the developed formulation is anticipated to establish a stable domestic supply chain and concurrently reduce national healthcare costs. These research findings also establish the groundwork for future continuous manufacturing implementation. Full article

Ibuprofen (IBU), paracetamol (PARA), and diclofenac (DIC) are three of the most used non-opioid analgesics and are most frequently detected in the environment. Some methods to analyze these compounds in water have been previously reported, but they have limitations such as long analysis time, high reagent consumption, and lack of sensitivity. An electrospray ionization high-performance liquid chromatography–mass spectrometry (ESI-HPLC-MS/MS)-based method was developed for the determination of these analgesics, applying 3D printing to improve the extraction process. The method was validated and applied to quantify the target pharmaceuticals using commercial tablets. For PARA and DIC, a gradient elution with 0.1% formic acid in water (A) and 0.1% formic acid in acetonitrile (B) was employed. For the analysis of IBU, an isocratic elution with 10 mM acetate in water (A) and acetonitrile (B) was used. ESI-MS/MS spectra were obtained in positive polarity to identify DIC and PARA, while negative polarity was used for IBU. LOD were 40.91, 3.64, and 1.96, and the LOQ were 136.36, 12.15, and 6.52 ng/L for IBU, PARA, and DIC, respectively. R² was >0.99 and RSD < 10% in all cases. The 3D-printed extraction device can be used for up to 10 cycles. This method demonstrated a remarkable performance compared to previous studies, mainly in terms of precision (RSD = 0.6–4.16%), mobile phase consumption (4 mL), and analysis time (<7 min), and was applied in the analysis of surface water samples. Full article