Search Results (27)

Mixing polymeric excipients with drugs in amorphous solid dispersions (ASD) is known to enhance the bioavailability of drugs by inhibiting their recrystallisation. However, the mechanisms underlying stabilisation remain not fully understood. This study aims to improve our understanding of the role of dynamics, particularly the molecular movements that drive instabilities, through investigations of ASD made of Polyvinylpyrrolidone (PVP K12) and a model drug, Terfenadine. The analyses combine temperature modulated differential scanning calorimetry (MDSC) and dielectric relaxation spectroscopy. The results reveal that the produced ASDs are supersaturated with Terfenadine, regardless of the content, and that PVP slows down the dynamics of the blends, limiting the recrystallisation of the drug during heating. Although the ASDs appear homogeneous based on thermal analysis with a single glass transition consistently detected by MDSC, the investigation of the dynamics reveals a dissociation of the main relaxation into two components for PVP contents below 30 wt.%. This dynamic heterogeneity suggests a structural heterogeneity with the coexistence of two amorphous phases of different compositions, each characterised by its own dynamics. The complex evolution of these dynamics under recrystallisation is rationalised by the confrontation with the phase and state diagram of Terfenadine/PVP blends established by MDSC. Full article

Background: It is generally accepted that water as a plasticizer can decrease the glass transition temperatures (T_gs) of amorphous drugs and drug delivery systems, resulting in physical instabilities. However, a recent study has reported an anti-plasticizing effect of water on amorphous lidocaine (LID). In co-amorphous systems, LID might be used as a co-former to impair the plasticizing effect of water. Method: Flurbiprofen (FLB) was used to form a co-amorphous system with a mole fraction of LID of 0.8. The effect of water on the stability of co-amorphous FLB-LID upon hydration was investigated. The crystallization behaviors of anhydrous and hydrated co-amorphous FLB-LID systems were measured by an isothermal modulated differential scanning calorimetric (iMDSC) method. The relaxation times of the co-amorphous FLB-LID system upon hydration were measured by a broadband dielectric spectroscopy (BDS), and the differences in Gibbs free energy (ΔG) and entropy (ΔS) between the amorphous and crystalline phases were determined by differential scanning calorimetry (DSC). Results: It was found that the crystallization tendency of co-amorphous FLB-LID decreased with the addition of water. Molecular mobility and thermodynamic factors were both investigated to explain the difference in crystallization tendencies of co-amorphous FLB-LID upon hydration. Conclusions: The results of the study showed that LID could be used as an effective co-former to decrease the crystallization tendency of co-amorphous FLB-LID upon hydration by enhancing the entropic (ΔS) and thermodynamic activation barriers (TΔS)³/ΔG²) to crystallization. Full article

Background/Objectives: This study evaluates the efficacy of twin screw melt granulation (TSMG), and hot-melt extrusion (HME) techniques in enhancing the solubility and dissolution of simvastatin (SIM), a poorly water-soluble drug with low bioavailability. Additionally, the study explores the impact of binary polymer blends on the drug’s miscibility, solubility, and in vitro release profile. Methods: SIM was processed with various polymeric combinations at a 30% w/w drug load, and a 1:1 ratio of binary polymer blends, including Soluplus^® (SOP), Kollidon^® K12 (K12), Kollidon^® VA64 (KVA), and Kollicoat^® IR (KIR). The solid dispersions were characterized using modulated differential scanning calorimetry (M-DSC), powder X-ray diffraction (PXRD), and Fourier-transform infrared spectroscopy (FTIR). Dissolution studies compared the developed formulations against a marketed product. Results: The SIM-SOP/KIR blend showed the highest solubility (34 µg/mL), achieving an approximately 5.5-fold enhancement over the pure drug. Dissolution studies showed that SIM-SOP/KIR formulations had significantly higher release profiles than the physical mixture (PM) and pure drug (p < 0.01). Additionally, their release was similar to a marketed formulation, with 100% drug release within 30 min. In contrast, the SIM-K12/KIR formulation exhibited strong miscibility, but limited solubility and slower release rates, suggesting that high miscibility does not necessarily correlate with improved solubility. Conclusions: This study demonstrates the effectiveness of TSMG, and HME as effective continuous manufacturing technologies for improving the therapeutic efficacy of poorly water-soluble drugs. It also emphasizes the complexity of polymer–drug interactions and the necessity of carefully selecting compatible polymers to optimize the quality and performance of pharmaceutical formulations. Full article

The present study investigated the effect of different polymers and manufacturing methods (hot melt extrusion, HME, and spray drying, SD) on the solid state, stability and pharmaceutical performance of amorphous solid dispersions. In the present manuscript, a combination of different binary amorphous solid dispersions containing 20% and 30% of drug loadings were prepared using SD and HME. The developed solid-state properties of the dispersions were evaluated using small- and wide-angle X-ray scattering (WAXS) and modulated differential scanning calorimetry (mDSC). The molecular interaction between the active pharmaceutical ingredients (APIs) and polymers were investigated via infrared (IR) and Raman spectroscopy. The in vitro release profile of the solid dispersions was also evaluated to compare the rate and extend of drug dissolution as a function of method of preparation. Thereafter, the effect of accelerated stability conditions on the physicochemical properties of the solid dispersions were also evaluated. The results demonstrated higher stability of Soluplus^® (SOL) polymer-based solid dispersions as compared to hydroxypropyl methylcellulose (HPMC)-based solid dispersions. Moreover, the stability of the solid dispersions was found to be higher in the case of API having high glass transition temperature (Tg) and demonstrated higher interaction with the polymeric groups. Interestingly, the stability of the melt-extruded dispersions was found to be slightly higher as compared to the SD formulations. However, the down-processing of melt-extruded strands plays critical role in inducing the API crystal nuclei formation. In summary, the findings strongly indicate that the particulate properties significantly influence the performance of the product. Full article

Here, we report work on developing an enzymatic process to improve the functionalities of industrial lignin. A kraft lignin sample prepared from marine pine was treated with the high-redox-potential laccase from the basidiomycete fungus Pycnoporus cinnabarinus at three different concentrations and pH conditions, and with and without the chemical mediator 1-hydroxybenzotriazole (HBT). Laccase activity was tested in the presence and absence of kraft lignin. The optimum pH of PciLac was initially 4.0 in the presence and absence of lignin, but at incubation times over 6 h, higher activities were found at pH 4.5 in the presence of lignin. Structural changes in lignin were investigated by Fourier-transform infrared spectroscopy (FTIR) with differential scanning calorimetry (DSC), and solvent-extractable fractions were analyzed using high-performance size-exclusion chromatography (HPSEC) and gas chromatography–mass spectrometry (GC–MS). The FTIR spectral data were analyzed with two successive multivariate series using principal component analysis (PCA) and ANOVA statistical analysis to identify the best conditions for the largest range of chemical modifications. DSC combined with modulated DSC (MDSC) revealed that the greatest effect on glass transition temperature (Tg) was obtained at 130 U g cm⁻¹ and pH 4.5, with the laccase alone or combined with HBT. HPSEC data suggested that the laccase treatments led to concomitant phenomena of oligomerization and depolymerization, and GC–MS revealed that the reactivity of the extractable phenolic monomers depended on the conditions tested. This study demonstrates that P. cinnabarinus laccase can be used to modify marine pine kraft lignin, and that the set of analytical methods implemented here provides a valuable tool for screening enzymatic treatment conditions. Full article

Highly methylated apple pectin (HMAP) and pork gelatin (PGEL) have been proposed as gelling agents for pumpkin purée-based films. Therefore, this research aimed to develop and evaluate the physiochemical properties of composite vegetable films. Granulometric analysis of film-forming solutions showed a bimodal particle size distribution, with two peaks near 25 µm and close to 100 µm in the volume distribution. The diameter D_4.3, which is very sensitive to the presence of large particles, was only about 80 µm. Taking into account the possibility of creating a polymer matrix from pumpkin purée, its chemical characteristic was determined. The content of water-soluble pectin was about 0.2 g/100 g fresh mass, starch at the level of 5.5 g/100 g fresh mass, and protein at the level of about 1.4 g/100 g fresh mass. Glucose, fructose, and sucrose, the content of which ranged from about 1 to 1.4 g/100 g fresh mass, were responsible for the plasticizing effect of the purée. All of the tested composite films, based on selected hydrocolloids with the addition of pumpkin purée, were characterized by good mechanical strength, and the obtained parameters ranged from about 7 to over 10 MPa. Differential scanning calorimetry (DSC) analysis determined that the gelatin melting point ranged from over 57 to about 67 °C, depending on the hydrocolloid concentration. The modulated differential scanning calorimetry (MDSC) analysis results exhibited remarkably low glass transition temperature (Tg) values, ranging from −34.6 to −46.5 °C. These materials are not in a glassy state at room temperature (~25 °C). It was shown that the character of the pure components affected the phenomenon of water diffusion in the tested films, depending on the humidity of the surrounding environment. Gelatin-based films were more sensitive to water vapor than pectin ones, resulting in higher water uptake over time. The nature of the changes in water content as a function of its activity indicates that composite gelatin films, with the addition of pumpkin purée, are characterized by a greater ability to adsorb moisture from the surrounding environment compared to pectin films. In addition, it was observed that the nature of the changes in water vapor adsorption in the case of protein films is different in the first hours of adsorption than in the case of pectin films, and changes significantly after 10 h of the film staying in an environment with relative humidity RH = 75.3%. The obtained results showed that pumpkin purée is a valuable plant material, which can form continuous films with the addition of gelling agents; however, practical application as edible sheets or wraps for food products needs to be preceded with additional research on its stability and interactions between films and food ingredients. Full article

This paper is dealing with the dissolution mechanism of crystalline sulindac into amorphous Polyvinylpyrrolidone (PVP) upon heating and annealing at high temperatures. Special attention is paid on the diffusion mechanism of drug molecules in the polymer which leads to a homogeneous amorphous solid dispersion of the two components. The results show that isothermal dissolution proceeds through the growth of polymer zones saturated by the drug, and not by a progressive increase in the uniform drug concentration in the whole polymer matrix. The investigations also show the exceptional ability of temperature Modulated Differential Scanning Calorimetry (MDSC) to identify the equilibrium and out of equilibrium stages of dissolution corresponding to the trajectory of the mixture into its state diagram. Full article

Curcuma is a world-renowned herb known for its immense health benefits. In this study, physicochemical analyses were performed on the curcumin standard sample and curcumin multiple emulsions. The emulsions were analysed for thermal and structural stability for 21 days. Confocal laser microscopy (CLSM) was performed in order to observe the emulsion encapsulation. Modulated differential scanning calorimetry (MDSC) and HPLC methods revealed a variety of curcuminoids (curcumin, demethoxycurcumin, bisdemethoxycurcumin, and cyclocurcumin) in the investigated curcumin standard. In addition, the MDSC method was found to be suitable and comparable to HPLC for determining the curcuminoid substances. The analysis of the curcumin release revealed a value of 0.18 w.% after 14 days as the equilibrium value. Furthermore, an increase in the sizes of the emulsions was observed at the end of the 21-day study. The emulsion stability index (ESI) was used to measure the stability of multiple emulsions. The ESI reached 55.8% between 7 and 21 days later. Nano droplets of the oil phase loaded with dispersed curcumin particles captured inside the water-based carboxymethylcellulose micelles were clearly observed by CLSM. Full article

A functional food as a matrix based on a blend of carbohydrate polymers (25% maltodextrin and 75% inulin) with quercetin and Bacillus claussi to supply antioxidant and probiotic properties was prepared by spray drying. The powders were characterized physiochemically, including by moisture adsorption isotherms, X-ray diffraction (XRD), scanning electron microscopy (SEM), and modulated differential scanning calorimetry (MDSC). The type III adsorption isotherm developed at 35 °C presented a monolayer content of 2.79 g of water for every 100 g of dry sample. The microstructure determined by XRD presented three regions identified as amorphous, semicrystalline, and crystalline-rubbery states. SEM micrographs showed variations in the morphology according to the microstructural regions as (i) spherical particles with smooth surfaces, (ii) a mixture of spherical particles and irregular particles with heterogeneous surfaces, and (iii) agglomerated irregular-shape particles. The blend’s functional performance demonstrated antioxidant activities of approximately 50% of DPPH scavenging capacity and viability values of 6.5 Log10 CFU/g. These results demonstrated that the blend displayed functional food behavior over the complete interval of water activities. The equilibrium state diagram was significant for identifying the storage conditions that promote the preservation of functional food properties and those where the collapse of the microstructure occurs. Full article

Frozen food is exposed to inevitable temperature changes during its storage, transport, and at the point of sale, which implies a significant impact on its properties and quality. Thus, the study of the effect of the formation of crystals on both the surface of the meat and the container when it is kept frozen, involving the thermodynamic analysis and changes that occurred at the structural level, is necessary. In this research, pork meat from Longissimus thoracis muscle was used, which was cut into plates and packed with two types of food-grade films: (1) Polyvinyl Chloride (PVC) and (2) low-density polyethylene (LDPE). Samples were frozen by indirect contact with nitrogen up to −40 ± 0.5 °C and subsequently stored at −20 ± 1 °C in a chamber from 0 to 15 days. The frost thickness was evaluated by the image superposition method. FTIR spectra were obtained by means of an Attenuated Total Reflectance (ATR) accessory, and thermal changes were determined by Modulated Differential Scanning Calorimetry (MDSC). It was found that the thickness of the frost on the surface of the meat is less when it is packaged with PVC due to the characteristics of the polymer matrix of the package. Furthermore, there were important changes at the molecular level identified by FTIR and MDSC, indicating significant differences (p < 0.05) between the samples. In general, PVC films were more stable at lower temperatures, allowing a small number of changes in the meat surface due to temperature fluctuations. Full article

The formulation of poorly water-soluble drugs is one of the main challenges in the pharmaceutical industry, especially in the development of oral dosage forms. Meanwhile, there is an increase in the number of poorly soluble drugs that have been discovered as new chemical entities. It was also reported that the physical transformation of a drug from a crystalline form into an amorphous state could be used to increase its solubility. Therefore, this study aims to evaluate the pharmaceutical properties of amorphous drug loaded-mesoporous silica (MPS) and pure amorphous drugs. Ritonavir (RTV) was used as a model of a poorly water-soluble drug due to its low recrystallization tendency. RTV loaded-MPS (RTV/MPS) and RTV amorphous were prepared using the solvent evaporation method. Based on observation, a halo pattern in the powder X-ray diffraction pattern and a single glass transition (T_g) in the modulated differential scanning calorimetry (MDSC) curve was discovered in RTV amorphous, indicating its amorphization. The T_g was not detected in RTV/MPS, which showed that the loading RTV was completed. The solid-state NMR and FT-IR spectroscopy also showed the interaction between RTV and the surface of MPS in the mesopores. The high supersaturation of RTV was not achieved for both RTV/MPS and the amorphous state due to its strong interaction with the surface of MPS and was not properly dispersed in the medium, respectively. In the dissolution test, the molecular dispersion of RTV within MPS caused rapid dissolution at the beginning, while the amorphous showed a low rate due to its agglomeration. The stability examination showed that the loading process significantly improved the physical and chemical stability of RTV amorphous. These results indicated that the pharmaceutical properties of amorphous drugs could be improved by loaded-MPS. Full article

Soil-specific heat capacity (c_p) and volumetric heat capacity (C_v) are recognized as a fundamental soil property essential for the accurate prediction of soil temperature and heat flow. This study presents the analysis of these thermal properties for drained peat soils in Poland. The objectives of this study were to (i) measure and develop a method for determining c_p, (ii) analyze the (C_v) data for undisturbed soil samples from surface layers, and (iii) test the applicability of the c_p value for calculating C_v of drained peat soils using the mixing model concept. The c_p value was measured under laboratory conditions using a modulated differential scanning calorimetry (MDSC) for 18 soil layers sampled in six degraded peat soil profiles. The C_v was estimated for undisturbed triplicate soil samples from the 22 depths (66 samples) by using a dual-needle probe. The c_p data for the organic soils were linearly temperature-dependent (MDSC) for the temperature range considered (−20–30 °C). The overall average c_p value was equal to 1.202 J g⁻¹ K⁻¹ at a temperature of 0 °C. An increment in temperature of 1 °C corresponded to an increase in c_p of 0.0043 J g⁻¹ K⁻¹ on average. Nevertheless, the lowest c_p value was obtained for moss samples whereas the highest value represents alder peats. The C_v data measured using the heat thermal probe (HTP) method changed linearly with changes in the soil moisture content (θ_v) of the moorsh soils. The volumetric heat capacity calculated using the mixing model was comparable to the mean of measured values obtained on the triplicate samples. Full article

Chocolate-coated fruit is becoming more and more popular as a tasty snack. The subjects of the research were freeze-dried strawberries and dark and milk chocolate-coated freeze-dried strawberries. The DSC curves, sorption isotherms, and glass transition temperature were determined. The state diagrams of the freeze-dried strawberries and dark and milk chocolate-coated freeze-dried strawberries were investigated. The modulated differential scanning calorimetry (MDSC) technique was used to determine the glass transition temperature. The DSC diagrams of the studied samples showed differences in shape and course. The sorption isotherms of the freeze-dried strawberries and dark and milk chocolate-coated strawberries belonged to type II according to BET classification. A coating of milk or dark chocolate resulted in a significant reduction in the hygroscopic behaviour of the freeze-dried strawberries and could be considered a promising way to improve the shelf life of the product and improve the nutritional value for commercial production purposes. Full article

The incorporation of a drug into mesoporous silica (MPS) is a promising strategy to stabilize its amorphous form. However, the drug within MPS has shown incomplete release, despite a supersaturated solution being generated. This indicates the determination of maximum drug loading in MPS below what is experimentally necessary to maximize the drug doses in the system. Therefore, this study aimed to characterize the drugs with good glass former loaded-mesoporous silica, determine the maximum drug loading, and compare its theoretical value relevance to monolayer covering the mesoporous (MCM) surface, as well as pore-filling capacity (PFC). Solvent evaporation and melt methods were used to load each drug into MPS. In addition, the glass transition of ritonavir (RTV) and cyclosporine A (CYP), as well as the melting peak of indomethacin (IDM) and saccharin (SAC) in mesoporous silica, were not discovered in the modulated differential scanning calorimetry (MDSC) curve, demonstrating that each drug was successfully incorporated into the mesopores. The amorphization of RTV-loaded MPS (RTV/MPS), CYP-loaded MPS (CYP/MPS), and IDM-loaded MPS (IDM/MPS) were confirmed as a halo pattern in powder X-ray diffraction measurements and a single glass transition event in the MDSC curve. Additionally, the good glass formers, nanoconfinement effect of MPS and silica surface interaction contributed to the amorphization of RTV, CYP and IDM within MPS. Meanwhile, the crystallization of SAC was observed in SAC-loaded MPS (SAC/MPS) due to its weak silica surface interaction and high recrystallization tendency. The maximum loading amount of RTV/MPS was experimentally close to the theoretical amount of MCM, showing monomolecular adsorption of RTV on the silica surface. On the other hand, the maximum loading amount of CYP/MPS and IDM/MPS was experimentally lower than the theoretical amount of MCM due to the lack of surface interaction. However, neither CYP or IDM occupied the entire silica surface, even though some drugs were adsorbed on the MPS surface. Moreover, the maximum loading amount of SAC/MPS was experimentally close to the theoretical amount of PFC, suggesting the multilayers of SAC within the MPS. Therefore, this study demonstrates that the characterization of drugs within MPS, such as molecular size and interaction of drug-silica surface, affects the loading efficiency of drugs within MPS that influence its relevance with the theoretical value of drugs. Full article

A functional food based on blends of carbohydrate polymers and active ingredients was prepared by spray drying. Inulin (IN) and maltodextrin (MX) were used as carrying agents to co-microencapsulate quercetin as an antioxidant and Bacillus clausii (Bc) as a probiotic. Through a reduced design of experiments, eleven runs were conducted and characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), and modulated differential scanning calorimetry (MDSC). The physical characterizations showed fine and non-aggregated powders, composed of pseudo-spherical particles with micrometric sizes. The observation of rod-like particles suggested that microorganisms were microencapsulated in these particles. The microstructure of the powders was amorphous, observing diffraction peaks attributed to the crystallization of the antioxidant. The glass transition temperature (Tg) of the blends was above the room temperature, which may promote a higher stability during storage. The antioxidant activity (AA) values increased for the IN-MX blends, while the viability of the microorganisms increased with the addition of MX. By a surface response plot (SRP) the yield showed a major dependency with the drying temperature and then with the concentration of IN. The work contributes to the use of carbohydrate polymers blends, and to the co-microencapsulation of active ingredients. Full article