Search Results (170)

Background: The solubility and phase behavior of APIs are crucial for the development of medicines and ensuring their stability. However, conventional experimental approaches often do not allow for the precise determination of phase transitions and solubility limits, especially for poorly soluble compounds. Purpose: The aim of this study was to demonstrate the possibility of using the laser microinterferometry method, traditionally used to define the phase equilibria of polymer systems, to determine the thermodynamic solubility of the APIs. Methods: Using laser microinterferometry, the thermodynamic solubility and phase behavior of amorphous darunavir were determined in various pharmaceutical solvents, including vaseline and olive oils, water, glycerol, alcohols (methanol, ethanol, isopropanol), glycols (propylene glycol, polyethylene glycol 400, polypropylene glycol 425, polyethylene glycol 4000), and ethoxylated polyethylene glycol ether obtained from castor oil in the temperature range of 25–130 °C. Dissolution kinetics was estimated at 25 °C. Hansen solubility parameter calculations were also performed for comparison. Results: Darunavir is practically insoluble in olive and vaseline oils. In water and glycerol, an amorphous equilibrium with an upper critical solution temperature was observed, and phase diagrams were constructed for the first time. In alcohols, glycols, and ethoxylated polyethylene glycol ether obtained from castor oil, darunavir showed high solubility, accompanied by the formation of crystalline solvates. Kinetic evaluation showed that the dissolution rate of darunavir in methanol is four times faster than in ethanol and thirty times faster than in isopropanol. Comparison of the obtained data with previously published and calculated values of solubility parameters demonstrates a good correlation. Conclusions: Laser microinterferometry has been demonstrated as a potential tool for determining the thermodynamic solubility of APIs. This method allows for directly observing the dissolution process, determining the solubility limits, and detecting phase transitions. These studies are necessary for selecting appropriate excipients, preventing the formation of undesirable solvates and predicting formulation stability, which are all critical factors in early-stage drug development and pharmaceutical formulation design. Full article

Vitamins are chemical compounds, or a group of closely related compounds known as vitamers, which are crucial for an organism’s metabolic functions. Vitamins are categorized as either water-soluble or fat-soluble, with this second group composed of vitamins A, D, E, and K. The low aqueous solubility of these compounds often necessitates the use of pharmaceutical excipients to benefit from their medicinal efficiency. A successful example of this is the formation of the inclusion complexes with cyclodextrins (CDs), a group of cyclic oligosaccharides, composed of glucose subunits forming a macrocyclic ring. CD complexes with fat-soluble vitamins have been consistently utilized to accomplish diverse objectives, with CDs predominantly employed as solubilizers and absorption enhancers. This article examines studies detailing the synthesis and the biological, physicochemical, and structural characteristics of the inclusion complexes formed between fat-soluble vitamins and different cyclodextrins. This research demonstrates that although the fat-soluble vitamins form stable complexes with various CDs, the kind of CDs employed significantly influences the resultant properties of the complex formed. Full article

Background/Objectives: Levocetirizine (LCZ) is a second-generation antihistamine with minimal central nervous system effects. However, its short half-life necessitates daily dosing, potentially reducing adherence in pediatric populations. This study aimed to develop a long-acting injectable LCZ formulation by synthesizing lipophilic prodrugs and evaluating their physicochemical stability, enzymatic hydrolysis, and pharmacokinetics in vivo. Methods: Two prodrugs of LCZ, LCZ decanoate (LCZ-D) and LCZ laurate (LCZ-L), were synthesized via esterification with alkyl alcohols. The compounds were characterized using NMR, FT-IR, and DSC. Prodrugs were formulated with an oil-based vehicle (castor oil and benzyl benozate), and their hydrolysis was evaluated using porcine liver esterase (PLE) and rat plasma. Pharmacokinetic profiles were assessed in Sprague Dawley rats after oral or intramuscular administration. Stability was tested at 25 °C, 40 °C, and 60 °C for 6 weeks. Results: LCZ-D and LCZ-L exhibited first-order hydrolysis kinetics, with rates following the order of PLE (2.0 > 0.5 units/mL) > plasma > PLE (0.2 units/mL). The C_max of LCZ-D and LCZ-L were 13.95 and 5.12 ng/mL, respectively, with corresponding AUC_0–45d values of 6423.12 and 2109.22 h·ng/mL. Formulations containing excipients with lower log P values led to increased systemic exposure. All formulations maintained therapeutic plasma concentrations for over 30 days. The inclusion of the antioxidant BHT (0.03% v/v) improved oxidative stability, reducing degradation at 60 °C from 4.72% to 1.17%. Conclusions: All formulations demonstrated potential for the long-acting delivery of LCZ, maintaining therapeutic plasma levels for over 30 days. Moreover, the release behavior and systemic exposure could be effectively modulated by excipient selection. Full article

Background: Furosemide is a loop diuretic used extensively to treat adult and pediatric patients. In some hospitals, furosemide oral liquids are not available in stock, thus necessitating the extemporaneous preparation of the drug. This study evaluates the stability of on-the-spot formulations of furosemide oral suspensions from crushed tablets evaluated in various vehicles: Dextrose 50%, Dextrose 70%, Ora-Sweet, and Ora-Plus over 60 days. This examination was prompted by the frequent shortage of certain excipients in the hospital, leading to the need to switch to Dextrose 50% or Dextrose 70% when Ora-Sweet and Ora-Plus are out of stock. Methods: The extemporaneous furosemide oral suspensions were prepared following the same compounding method used in the pharmacy. The suspensions were maintained at 4 °C in the refrigerator and assessed immediately and later, on days 7, 14, 30, and 60. The assessed parameters included visual appearance, redispersion time, sedimentation volume, and pH levels for stability analysis. We also examined the drug content, dissolution of the suspension, and microbiological stability. Results: Initial examinations indicated that Dextrose 50% and Ora-Plus maintained pH levels and stable appearances, while significant changes, mainly in appearance and redispersion time, indicated the instability of Dextrose 70%. Ora-Sweet showed fluctuations but stabilized by day 30. Dissolution studies demonstrated that Ora-Plus had dissolution characteristics superior to the other formulations, while Dextrose 50% showed declining dissolution percentages over time. Overall, the Ora-Plus vehicle showed superior stability (60 days), followed by Ora-Sweet (30 days), while Dextrose 70% and Dextrose 50% showed shorter stability durations of 14 and 7 days, respectively. The microbiological test results showed no microbial growth. Conclusions: This study demonstrates that the vehicle used in extemporaneous furosemide suspensions critically affects their stability and performance. Ora-Plus emerged as the most suitable vehicle, maintaining physical, chemical, and microbiological stability over 60 days, with consistent pH, redispersion, and dissolution behavior. Ora-Sweet showed intermediate stability (30 days), while Dextrose 50% and 70% exhibited early instability—7 and 14 days, respectively—marked by sedimentation, poor redispersibility, and declining drug release. These findings underscore the importance of vehicle selection and regular stability monitoring in compounded formulations to ensure therapeutic reliability and patient safety. Full article

Background: Pharmaceutical compounding remains a predominantly manual process with limited innovation, particularly in non-sterile applications. This study explores the implementation of an automated compounding platform based on 3D printing to enhance precision, efficiency, and adaptability in pediatric corticosteroid formulations. Methods: Personalized hydrocortisone dosage forms were prepared in a hospital pharmacy setting using a proprietary excipient base and standardized procedures, including automated dosing and syringe heating when required. Three dosage forms—3.2 mg gel tablets, 2.8 mg water-free troches, and 1.2 mg orodispersible films (ODFs)—were selected to demonstrate the platform’s versatility and to address pediatric needs for varying strengths and dosage types. All products were prepared using a reproducible semi-solid extrusion (SSE)-based workflow with the consistent API-excipient blending and automated deposition. Results: Analytical testing confirmed that all formulations met pharmacopeial criteria for mass and content uniformity. The ODF and troche forms achieved rapid drug release, exceeding 75% within 5 min, while the gel tablet showed a slower release profile, reaching 86% by 60 min. Additionally, in-process homogeneity testing across syringe printing cycles confirmed the consistent API distribution. Conclusions: The results support the feasibility of integrating automated compounding technologies into pharmacy workflows. Such systems can improve accuracy, minimize variability, and streamline the production of customized pediatric medications, particularly for drugs with poor palatability or narrow therapeutic windows. Overall, this study highlights the potential of automation to modernize non-sterile compounding, and to better support individualized therapy. Full article

Many studies are being conducted on the detection of nitrosamine impurities in solid formulations. However, research on semi-solid formulations such as gels, ointments and creams is not common. In particular, excipients used to increase viscosity and add fragrance can significantly impact the sample preparation. Volatile compounds derived from natural fragrances are composed of a wide variety of complex components, making them very difficult to handle and completely separate from the analytes. Due to the complex composition of these formulations, an analytical method was developed to accurately separate and analyze nine nitrosamine impurities (NDMA, NDEA, NMEA, NDPA, NDBA, NPIP, NMOR, DIPNA and EIPNA) simultaneously. To overcome challenges in the sample preparation of excipients with physical and chemical properties, the sample was prepared using solvents such as methanol, hexane, water and dichloromethane. The target analytes were extracted with dichloromethane for the final preparation for GC–MS/MS and the optimal conditions were established. While multiple GC columns were tested, peak overlapping interferences were observed, leading to the use of a 60m-long column to overcome peak overlap. The GC–MS/MS condition was set for optimal performance and ionization energy, with parameters adjusted for each analyte. The developed method was validated in accordance with guidelines to ensure its reliability and suitability. As a result, all nine nitrosamine impurities were simultaneously analyzed, confirming excellent performance. The sample preparation method and procedure, column specification and GC–MS/MS conditions have the potential to be adapted not only for semi-solid formulations of pharmaceuticals and cosmetics but also for other formulations such as solid and liquid samples, rendering them suitable for the analysis of nitrosamine impurities. Full article

Background: Zinc oxide paste is traditionally compounded and applied in the therapy of various skin conditions. However, prolonged use of talc, usually present in zinc oxide pastes, may pose health risks due to potential contamination with asbestos and quartz, highlighting the need for alternative excipients. This study aimed to examine the effects of starches from various botanical sources and their particle size on the rheological and absorption properties of zinc oxide paste. Methods: Eight zinc oxide paste formulations were prepared, containing 25% zinc oxide and 25% indifferent excipient (talc, tapioca, rice, or maize starch) in two particle sizes. Rheological properties were assessed using amplitude and frequency sweep tests, and water- and oil-absorption capacities were determined using a centrifugation-based method. Results: Amplitude sweep tests confirmed the predominant solid-like nature of zinc oxide pastes, with the elastic modulus (G′) exceeding the viscous modulus (G″) in all formulations. Tapioca starch-based pastes exhibited the highest G′ and G″ values, while talc-based pastes exhibited the lowest. Frequency sweep tests showed that pastes were resistant to structural changes under stress, with G′ consistently dominating over G″ across the entire frequency range. Tapioca starch-based formulations exhibited the highest water-absorption capacity, while the talc-based formulations had the highest oil-absorption capacity. Reducing particle size improved both water- and oil-absorption capacities. Conclusions: Starches may be considered as alternatives to talc in zinc oxide pastes, due to their ability to modify the absorption and rheological properties of pastes. Future studies should assess the impact of starch substitution on sensory characteristics, shelf-life stability, and patient satisfaction. Full article

The food-induced viscosity of the media can alter tablet disintegration and eventually the release of the drug it contains. The extent of this retardation depends on tablet formulation factors, such as the solubility of its excipients. Objectives: This research aimed to study the effect of filler solubility on the disintegration and dissolution of tablets under different testing conditions. Methods: Tablet formulations containing acetaminophen (as a model compound), mixtures of different ratios of fillers, and other excipients were directly compressed using uniform manufacturing parameters. These formulations were investigated under fasted- and fed-state conditions to determine the influence of viscosity on their disintegration, inspired by the liquid penetration ratio (LPR) theoretical framework. Disintegration and dissolution tests were performed using both compendial and novel testing apparatuses. Results: The soluble fillers in the tablets affected their disintegration and dissolution in the simulated fed-state medium, while fasted-state conditions affected the tablets only marginally. The testing devices showed partially contrasting results, which appeared to be due to the hydrodynamics of the testing media used. The novel CNC (computed numerical control) apparatus offered 3D motion and effectively exposed the tablets to the viscous testing media, unlike the compendial paddle apparatus. Conclusions: This study explored the impact of filler solubility on the disintegration and dissolution of tablets. As the LPR framework revealed, fillers with a higher solubility have positive effects on the disintegration and dissolution of tablets in viscous conditions. Additionally, the proportion of soluble filler used is also inversely correlated with the disintegration time. Further investigation of the formulation parameters, as well as the testing conditions, would provide additional insights into the effects of food on these tablets. Full article

Most novel active pharmaceutical ingredients have low water solubility; therefore, solubility-enhancing methods are applied. The aim of the present investigation is to study the impact of nine commonly used pharmaceutical excipients (fillers, surfactants, cyclodextrins, polymers) on solubility, permeability and their relationship. This is crucial for ensuring optimal bioavailability. Carbamazepine, naproxen and pimobendan were chosen as model compounds due to their different acid–base properties. Equilibrium solubility was measured by the traditional shake flask method. Effective permeability was determined by the PAMPA model. Measurements of ionizable compounds were carried out at three pH values. The pH-dependent change in the investigated parameters is maintained even in the presence of excipients. Fillers resulted in a slight or no effect, while the impact of other excipients showed a significant concentration dependence. The impact of excipients was influenced by the structure and ionization state of the molecules. The dominance of the ionized form moderates the impact of excipients. The changes in solubility were more pronounced than in the case of permeability. By examining the effect of the ionization state and interactions with excipients, this work supports the development of formulations that enhance solubility with minimal impacts on permeability. Additionally, it can serve as good basis for preformulation studies and design optimization. Full article

In order to secure domestic microbial resources, a fruit-flavored yeast was selected, and a starter manufacturing technology was developed to evaluate its quality characteristics. Among 26 yeast strains analyzed using an electronic nose, Saccharomyces cerevisiae YM45 isolated from Makgeolli was identified as having high levels of methyl formate and propan-2-one, compounds that are associated with fruity and sweet aroma. A powdered starter was then produced with S. cerevisiae YM45, and its quality characteristics were analyzed. When cyclodextrin was used as an excipient, with water content at 4.7%, bacterial contamination was found to be 2.30 log CFU/g, which ensures quality and safety. The rehydration rate, assessed using a PBS buffer, showed a high survival rate of 8.7 log CFU/g, which is a suitable condition for preserving yeast activity. These findings suggest that domestically sourced microbial resources can serve as viable alternatives to imported strains, with potential applications in industrial fermentation. Full article

Background: D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), an amphiphilic derivative of natural vitamin E, functions as both a drug efflux inhibitor and a protector against enzymatic degradation and has been widely incorporated into nano-formulations for drug design and delivery. Objective: This systematic review evaluates TPGS-based organic nanocarriers, emphasizing their potential to enhance bioavailability of active compounds which include drugs and phytochemicals, improve pharmacokinetic profiles, and optimize therapeutic outcomes, eventually overcoming the limitations of conventional oral active compounds delivery. Search strategy: Data collection was carried out by entering key terms (TPGS) AND (Micelle OR Liposome OR Nanoparticle OR Nanotube OR Dendrimer OR Niosome OR Nanosuspension OR Nanomicelle OR Nanocrystal OR Nanosphere OR Nanocapsule) AND (Oral Bioavailability) into the Scopus database. Inclusion criteria: Full-text articles published in English and relevant to TPGS, which featured organic materials, utilized an oral administration route, and included pharmacokinetic study, were included to the final review. Data extraction and analysis: Data selection was conducted by two review authors and subsequently approved by all other authors through a consensus process. The outcomes of the included studies were reviewed and categorized based on the types of nanocarriers. Results: An initial search of the database yielded 173 records. After screening by title and abstract, 52 full-text articles were analyzed. A total of 21 papers were excluded while 31 papers were used in this review. Conclusions: This review concludes that TPGS-based organic nanocarriers are able to enhance the bioavailability of various active compounds, including several phytochemicals, leveraging TPGS’s amphiphilic nature, inhibition of efflux transporters, protection against degradation, and stabilization properties. Despite using the same excipient, variability in particle size, zeta potential, and encapsulation efficiency among nanocarriers indicates the need for tailored formulations. A comprehensive approach involving the development and standardized comparison of diverse TPGS-incorporated active compound formulations is essential to identify the optimal TPGS-based nanocarrier for improving a particular active compound’s bioavailability. Full article

This study investigates the phytochemical profile, antioxidant and anti-inflammatory properties, and 3D-printing application of Origanum vulgare L. ssp. hirtum extract. The extract revealed a diverse range of phenolic compounds, with rosmarinic acid as the predominant compound (47.76%). The extract showed moderate to high lipoxygenase inhibition (IC₅₀ = 32.0 µg/mL), suggesting its potential as an anti-inflammatory agent. It also exhibited strong antioxidant activity, with hydrogen peroxide scavenging (SC₅₀ = 99.2 µg/mL) and hydroxyl radical scavenging (IC₅₀ = 64.12 µg/mL) capabilities. In cellular studies, high concentrations (50 µg/mL and 100 µg/mL) significantly decreased intracellular ROS production in Caco-2 cells (reductions exceeding 53% and 64%, respectively). Moreover, the extract suppressed NO production in LPS-stimulated J774A.1 macrophages in a concentration-dependent manner. The study also explores the incorporation of the extract into 3D-printed gummies. The gels exhibited a shear-thinning behavior, which was essential for successful extrusion-based 3D printing. The incorporation of Origanum extract significantly influenced the mechanical strength and compaction properties of the 3D-printed gummies before breaking (1.6-fold increase) allowing for a better mouth feeling. PXRD and FTIR analyses confirmed the amorphous nature of the 3D-printed gummies and the interaction between active ingredients and excipients utilized for printing. These findings demonstrated the potential for semisolid extrusion 3D printing at room temperature to transform a culinary herb (Origanum vulgare spp. hirtum) into a healthcare product with antioxidant and anti-inflammatory properties. Full article

This study establishes and validates a novel ultra-high-performance liquid chromatography (UHPLC) method for the determination of urolithin A content in health products, a bioactive compound with potential anti-aging properties. Given the lack of standardized analytical methods for urolithin A in health products, this research addresses a critical gap in quality control. The method employs a methanol–water mobile phase, optimized gradient elution, and a specialized UPLC column (ACQUITY UPLC CSH Fluoro Phenyl) to achieve high resolution and specificity in the separation of urolithin A from its impurities. A variety of diluents, extraction solvents, and extraction times were tested to maximize analyte recovery and stability, with pure methanol yielding the highest recovery rate (over 95%) in 30 min. The method was validated in terms of linearity, sensitivity, repeatability, specificity, and precision. The calibration curve for urolithin A exhibited excellent linearity (r² = 0.9998) over a concentration range of 0.100–10.000 µg/mL. Detection and quantification limits were found to be 0.051 µg/mL and 0.103 µg/mL, respectively. Precision testing revealed an inter-operator RSD of 1.3%, and recovery rates for spiked samples consistently fell within the 98–102% range. The developed method was successfully applied to analyze the urolithin A content in a commercially available health product, demonstrating its practicality for routine quality control. However, this method may currently be affected by the excipient matrix. This research contributes to the establishment of robust, reliable, and high-sensitivity analytical methods for the bioactive compounds found in health products, with significant implications for regulatory compliance and consumer safety. Full article

(1) Background: Ethanol is a multifunctional excipient often used as a preservative in topical formulations. Due to its known ability to impair skin barrier function, this study investigated the effect of ethanol (EtOH) as a preservative in creams on the dermal penetration of active compounds. (2) Methods: A hydrophilic and a lipophilic fluorescent dye were used as active ingredient surrogates that were incorporated into creams with and without ethanol. The dermal penetration efficacy was assessed by epifluorescence microscopy on an ex vivo porcine ear model with intact and irritated skin. (3) Results: Ethanol reduced the dermal penetration by about 40% for the hydrophilic and about 20% for the lipophilic surrogates on intact skin, but had minimal impact on irritated skin. The bio-physical skin properties were also altered by the addition of ethanol to the cream. On intact skin, it increased transepidermal water loss (TEWL) and decreased skin hydration, whereas on irritated skin, it decreased TEWL and increased skin hydration. The results indicate that skin impairment can be considered to have different stages, while in an early stage of skin impairment, the formation of a “Pudding skin” is proposed. A “Pudding skin” is the formation of a thin layer of dried skin on top of the skin that “seals” the lower parts of the skin and reduces dermal penetration and water loss from inside the skin and reduces the dermal penetration of chemical compounds from outside the skin. (4) Conclusions: Overall, the findings emphasize the need to carefully consider the use of ethanol in formulations, balancing its preservative benefits with its potential to impair the efficacy of active ingredients, particularly in varying skin conditions. Full article

Exposure to ultraviolet (UV) radiation from the sun significantly damages the skin, leading to premature aging, hyperpigmentation, and oxidative stress that disrupts skin homeostasis. UV radiation increases the production of reactive oxygen species (ROS), accelerating skin deterioration. Although sunscreens remain the primary method for UV protection, chemical-based formulations are often associated with side effects, such as allergic reactions and acne. To address these concerns, the inclusion of natural ingredients in sunscreen formulations has gained attention. Curcumin, an active compound found in turmeric (Curcuma longa) and Java turmeric (Curcuma xanthorrhiza), is well-known for its antioxidant and anti-inflammatory properties. This review explores the potential of curcumin as a natural ingredient for enhancing the Sun Protection Factor (SPF) of sunscreen products. A systematic literature review was conducted, analyzing 200 articles sourced from Google Scholar and PubMed using keywords such as “Curcumin”, “Curcuma”, “Antioxidant”, “Anti-Inflammatory”, and “Sun Protection Factor”. Studies unrelated to UV protection were excluded. The findings, presented in tabular form, indicate that curcumin and Curcuma exhibit significant potential to enhance SPF values due to their antioxidant, anti-inflammatory, and UV-absorbing properties. Additionally, curcumin may aid in skin repair following UV-induced damage. However, the specific concentration of curcumin in various Curcuma species remains unknown, and further research is necessary to determine its optimal use. Consideration of additional excipients in sunscreen formulations is also required to maximize efficacy. In conclusion, curcumin demonstrates considerable promise as a sustainable and effective natural ingredient for protecting the skin from UV radiation, offering a safer alternative to conventional chemical-based sunscreens. Full article