Accelerated Storage Conditions Research Articles

Simultaneous analysis of the oxidation of solvent-extracted and cold-pressed green coffee oil during accelerated storage using 1H NMR and 13C NMR spectroscopy

Green coffee oil (GCO) extracted from green coffee beans, is known for its antioxidant and anticancer properties, and has been increasingly utilised in cosmetic and other consumer products. However, lipid oxidation of GCO fatty acid components during storage may be harmful to human health, and there remains a need to understand the evolution of GCO chemical component oxidation. In this study, proton nuclear magnetic resonance (1H and 13C NMR) spectroscopy was used to investigate the oxidation status of solvent-extracted and cold-pressed GCO under accelerated storage conditions. Results show that the signal intensity of oxidation products gradually increased with increasing oxidation time, while unsaturated fatty acid signals gradually weakened. Five different types of GCO extracts were clustered according to their properties, except for minor overlapping in the two-dimensional plane of the principal component analysis. Partial least squares-least analysis results demonstrate that oxidation products (δ = 7.8–10.3 ppm), unsaturated fatty acids (δ = 5.28–5.42 ppm), and linoleic acid (δ = 2.70–2.85 ppm) in 1H NMR can be used as characteristic indicators of GCO oxidation levels. Furthermore, the kinetics curves of unsaturated fatty acids, linoleic, and linolenic acyl groups all fit an exponential equation with high coefficients of GCO for 36 days under accelerated storage conditions. Our results show that the current NMR system is a fast, easy-operated and convenient tool for the oxidation process monitoring and quality control of GCO.

Isolation, structural characterization and quantification of impurities in bupivacaine

Bupivacaine was found to be unstable during the accelerated storage condition(40 ℃ and 75% relative humidity), and two degradation impurities with the same protonated molecular ion were observed by high performance liquid chromatography-mass spectrometry (LC-MS). A semipreparative method was used to separate and purify the two impurities, and their structures were elucidated via comprehensive HR-MSMS and NMR spectroscopy analyses. Their stereo structures were characterized through single crystal X-ray diffraction. Meanwhile, an LC-MS method was developed and validated to quantify the two degradation impurities of bupivacaine. Chromatographic separation was performed on a C18 reversed-phase column (4.6 × 150 mm, 5 µm) using an equivalent elution with water and methanol. The limits of quantitation for the two degradation impurities (named RS1 and RS2) were 0.89 and 0.65 ng, respectively, and the average recoveries were in the range of 90∼108% and relative standard deviations were less than 5.0%. The proposed LC-MS method can be used to control the quality of bupivacaine and its formulations. Data AvailabilityData will be made available on request.

FORMULASI DAN UJI STABILITAS SEDIAAN MINUMAN ALKALI LIDAH BUAYA (Aloe vera. L) SEBAGAI ANTIOKSIDAN

Alkaline water is water with a higher pH level than normal drinking water, it has a pH between 7-9.5 and it also has antioxidant activity. Aloe vera (Aloe vera) contains nutrients, vitamins and minerals that can function as natural antioxidants, such as vitamins C, vitamins A, magnesium, and zinc. Fresh aloe vera is less acceptable and preferred because of its taste, so it is necessary to process A. vera into a more durable and acceptable product. This study aims at determining the best and acceptable A. vera alkaline drink formula through product stability testing, including organoleptic, pH measurement, microbiological test. Then, the selected formula is analysed for antioxidant activity using DPPH, while nutritional content testing including fat content, protein content, and carbohydrate content. The result of the stability test of alkaline A. vera drink with concentrations of F1 (10%), F2 (20%), and F3 (30%) after accelerated storage conditions at 5oC and 35oC organoleptically did not change, and ulfilled the requirements under the Minister of Health Regulation of the Food and Drug Administration number 13 of 2019, but the pH decreased because of oxidation reaction of phenolic compounds from A. vera gel which produced aloetic acid and chrysophanic acid. The hedonic test, a result of the selected formula was F3 (30%) had a strong antioxidant activity with an IC50 value of 9.952%, fat content 0.09%, protein content 0.16% and carbohydrate content 57.02%.

Influence of Anticaking Agents and Storage Conditions on Quality Characteristics of Spray Dried Apricot Powder: Shelf Life Prediction Studies Using Guggenheim-Anderson-de Boer (GAB) Model.

Apricot powder was developed through spray drying using gum arabic as an encapsulating material at a concentration of 19%. Inlet air temperature, feed total soluble solids (TSS), feed flow rate, and atomization speed were 190 °C, 23.0 °C, 300.05 mL/h, and 17,433 rpm, respectively. This study was therefore conducted to investigate the influence of anticaking agents (tricalcium phosphate and silicon dioxide) and storage conditions (ambient and accelerated) on physicochemical, micrometric, and thermal characteristics of spray-dried apricot powder (SDAP) packaged in aluminum laminates. Both tricalcium phosphate (TCP) and silicon dioxide (SiO2) improved the shelf life and quality of SDAP, with TCP being more effective, since a lower increase in water activity (aw), moisture content, degree of caking, hygroscopicity, and rehydration time was observed in TCP-treated samples followed by SiO2-treated samples than the control. Furthermore, flowability, glass transition temperature (Tg), and sticky-point temperature (Ts) of SDAP tended to decrease in a significant manner (p < 0.05) under both storage conditions. However, the rate of decrease was higher during accelerated storage. The water activity of treated samples under ambient conditions did not exceed 0.60 and had a total plate count within the permissible range of 40,000 CFU/g, indicating shelf stability of the powder. The predicted shelf life of powder obtained from the Guggenheim−Anderson−de Boer (GAB) model and experimental values were very similar, with TCP-treated samples having a predicted shelf life of 157 days and 77 days under ambient and accelerated storage conditions, respectively. However, the respective experimental shelf life under the same conditions was 150 and 75 days, respectively. Similarly, the predicted shelf life of SiO2-treated samples under ambient and accelerated storage was 137 and 39 days, respectively, whereas the experimental values were 148 and 47 days, respectively. In conclusion, TCP proved more effective than SiO2 at preserving shelf life by preventing moisture ingress.

Drop-on-powder 3D printing of amorphous high dose oral dosage forms: Process development, opportunities and printing limitations

Drop-on-powder 3D printing is able to produce highly drug loaded solid oral dosage forms. However, this technique is mainly limited to well soluble drugs. The majority of pipeline compounds is poorly soluble, though, and requires solubility enhancement, e.g., via formation of amorphous solid dispersions. This study presents a detailed and systematic development approach for the production of tablets containing high amounts of a poorly soluble, amorphized drug via drop-on-powder 3D printing (also known as binder jetting). Amorphization of the compound was achieved via hot-melt extrusion using the exemplary system of the model compound ketoconazole and copovidone as matrix polymer at drug loadings of 20% and 40%. The milled extrudate was used as powder for printing and the influence of inks and different ink-to-powder ratios on recrystallization of ketoconazole was investigated in a material-saving small-scale screening. Crystallinity assessment was performed using differential scanning calorimetry and polarized light microscopy to identify even small traces of crystallinity. Printing of tablets showed that the performed small-scale screening was capable to identify printing parameters for the development of amorphous and mechanically stable tablets via drop-on-powder printing. A stability study demonstrated physically stable tablets over twelve weeks at accelerated storage conditions.

Optimal conditions for anthocyanin extract microencapsulation in taro starch: Physicochemical characterization and bioaccessibility in gastrointestinal conditions

This research aims to find the optimal conditions for the encapsulation of anthocyanin extract using taro starch to increase the retention of active compounds (RAC), drying yield (DY), antioxidant activity, stability, and bioaccessibility. The microencapsulation is carried out in a spray dryer, and the process is optimized using response surface method (RSM), applying starch concentration and inlet air temperature as independent parameters. Optimized microcapsules (OM) are obtained with solids concentration of 20.9 % and inlet temperature of 125 °C as optimal conditions. Drying yield (70.1 %), moisture content (5.2 %), water activity (0.211), phenolic compound content (797.8 mg GAE/g), anthocyanins (469.4 mg CE3G/g), ABTS (116.2 mg AAE/g) and DPPH (104.4 mg AAE/g) are analyzed through RSM. Retention percentage in OM show values of 60 % in bioactive compounds up to four weeks of storage under accelerated storage conditions. Bioaccessibility of OM is 10 % higher than that observed in the extract without encapsulation during gastrointestinal digestion. The results in this study show that OM made with taro starch and obtained with RSM effectively protect through digestion and ensure bioactive compound stability during storage.

Microencapsulated olive leaf extract enhances physicochemical stability of biscuits

Free and microencapsulated olive leaves extracts (OLE) have been proposed as natural antioxidant to prolong the stability of biscuits, under two accelerated storage conditions, with and without UV light. The equivalent of 500 µg gallic acid/ g of dough has been selected as the sensory acceptable OLE concentration. Higher total phenol content and antioxidant activity were observed in biscuits enriched with both free (B-OLE) and microencapsulated (B-MCR) OLE, in comparison to the controls (B-C), being B-MCR less affected than B-OLE during storage. Higher oxidative stability was detected for B-MCR than B-OLE and B-C, when measured by both peroxide value and Oxitest. A general hardness decrease was observed for all the formulations during storage, being however B-MCR always harder than B-OLE and B-C, probably because of the interactions of the microsphere polymers (alginate and pectin) with water. Darker colours were measured for the enriched biscuits in comparison to the control ones, being all slightly affected during storage by water migration and lipid oxidation phenomena.

Shelf-life prediction of pot-honey subjected to thermal treatments based on quality attributes at accelerated storage conditions

Pot-honey is a highly valuable product obtained by stingless bees that commonly predominate in tropical habitats and constitutes an interesting alternative to the typical production and commercialization of Apis mellifera honey. Although the production in most places is purely artisanal, the prospect of growth in the commercialization of this type of honey is promising. However, there are still problems of handling and conservation, fundamentally linked to poor hygienic practices that lead to the proliferation of microorganisms. Since the water content in pot-honey is typically higher than reported for A. mellifera honey, it is more susceptible to degradation if treatments aimed at sanitizing the product are not carried out. In this sense, pasteurization is presented as an accessible alternative for beekeepers, but it does not guarantee the elimination of spores, which represent a risk to the health of consumers. In this study, tyndallization was tested as a method to sanitize pot-honey, based on heating/cooling cycles that promote spore germination, facilitating their elimination. The results found show treatment at 80 °C for 15 min promoted an increase in HMF levels and a decrease in diastase activity, although between the limits defined in regulations set for A. mellifera . The shelf-life study showed that free acidity limited the storage time, overpassing an acceptable value after 200 days at 23 °C. In conclusion, this study has demonstrated optimum conditions for honey processing through the elimination of the microbiological load it contains. Tyndallization is presented as a viable and accessible alternative for meliponiculturists to improve food hygiene and preserve it for a reasonable time under typical honey storage conditions. The information obtained will allow establishing the bases for adequate control of honey from T. angustula bees in the different stages of the distribution chain. • Pot-honey is a food commonly eaten raw despite its microbiological risk. • Pasteurization was not an effective treatment for spore inactivation in pot-honey. • Tyndallization of pot-honey promoted the germination and elimination of spores. • HMF increased but its value was lower than the maximum established in the regulations for A. mellifera . • It is shown a standardized procedure for pot-honey sanitation, that could be scaled and applied in food industry.

Estimation of shelf-life of Balachaturbhadrika syrup containing different sweetening agents

Background: Stability being the potential of any particular preparation in a noteworthy container/closure set up to abide within its physical, microbiological, chemical, toxicological, therapeutic stipulations which is invariably manifested in respect of shelf-life. Main aim of present analysis is to ascertain the shelf-life of Balachaturbhadrika Syrup prepared with different sweetening agent viz. Sugar (Sample I), Jaggery (Sample II), Honey (Sample III) and Stevia (Sample IV). The study was performed under accelerated storage conditions. Methods: Accelerated stability study was conducted for 3 months as per ICH guideline QA1 (R2) and the changes in physico-chemical traits viz. pH, refractive index, specific gravity, alcohol content and sedimentation rate were inscripted for quadruple alliance of 0, 15, 30 and 90 days. The statistical analysis was done using mean ± SEM, student paired t- test and Analysis of Variance (ANOVA). Results: Remarkable changes were found in both organoleptic and physico-chemical traits. Extrapolated shelf-life of Sample I, II, III and IV from physico-chemical attributes in conformity with the weather conditions prevailing in India were 73.514 month (6.12 year), 76.080 month (6.340 year), 58.05 month (4.83 year) and 37.05 month (3.09 year) respectively. Conclusion: The syrups prepared using Sugar, Jaggery and Honey were found to be more stable than those prepared using Stevia as the value of physical parameters was found more prominent for honey, jaggery and sugar.

Shelf‐life prediction of milk‐millet powders

AbstractMigration of moisture and oxygen into packages during storage lead to deteriorative reactions such as nonenzymatic browning (NEB), stickiness, caking, and oxidation. Actual shelf‐life testing of milk‐millet powders is tedious and time‐consuming as they have long storage stability. The aim of this study was to predict the shelf‐life of spray‐dried milk‐millet powders based on deteriorative reactions due to moisture and oxygen uptake, and evaluate whether the prediction models could be applied as an alternative to accelerated or normal shelf‐life testing. Fresh cow milk was standardized, concentrated to 22% total solids (TS), blended with millet wort of 22% TS in 1:1 ratio, and dried into powder using a lab‐scale co‐current type spray dryer. The predicted shelf‐life of milk‐malted foxtail millet powder based on stickiness and NEB caused by moisture gain was 17 and 30 days in high‐density polyethylene (HDPE), 41 and 58 days in EVOH laminate (LDPE/EVOH/LDPE), and 96 and 134 days in polyethylene‐terephthalate (PET) laminate (PET/Al foil/PET/LDPE) pouches, respectively. The corresponding shelf‐life of milk‐barnyard millet powder based on stickiness and NEB was 18 and 30 days, 66 and 96 days, and 90 and 102 days, in HDPE, EVOH laminate, and PET laminate, respectively. Similarly, the predicted oxygen limiting shelf‐life based on thiobarbituric acid reactive substances was found to be 40, 75, and 86 days for milk‐foxtail millet powder and 32, 72, and 93 days for milk‐barnyard millet powder in HDPE, EVOH laminate, and PET laminate, respectively. The rate of deteriorative reactions was the lowest in PET laminate pouches because of its excellent barrier properties over that of HDPE and EVOH even at the adverse accelerated storage conditions. The simulation model was adequate and reliable in predicting the shelf‐life of milk‐millet powders in packaging materials with wide range of barrier properties.Practical ApplicationsDeteriorative reactions such as caking and nonenzymatic browning induced by moisture, and oxidative reactions induced by ingress of oxygen into the package, affect the shelf‐life of milk‐millet powders. For such food powders having long shelf‐life, regular and accelerated shelf‐life testing are cumbersome and sometimes untenable. Simulation and mathematical modeling of shelf‐life is an alternative to long‐term shelf‐life tests. In this study, models for predicting the shelf‐life of milk‐millet powders based on moisture gain and oxygen uptake were developed. Prediction of shelf‐life will be helpful to monitor the product stability against spoilage by deteriorative reactions. The models could also be used for evaluation of shelf‐life of millet‐ and other food powders in flexible packaging materials. The prediction model not only required less time and resources but also was adequately reliable.

Variations in Antioxidant Capacity, Oxidative Stability, and Physicochemical Quality Parameters of Walnut (Juglans regia) Oil with Roasting and Accelerated Storage Conditions.

Walnut oil, like all vegetable oils, is chemically unstable because of the sensitivity of its unsaturated fatty acids to the oxidation phenomenon. This phenomenon is based on a succession of chemical reactions, under the influence of temperature or storage conditions, that always lead to a considerable change in the quality of the oil by promoting the oxidation of unsaturated fatty acids through the degradation of their C-C double bonds, leading to the formation of secondary oxidation products that reduce the nutritional values of the oil. This research examines the oxidative stability of roasted and unroasted cold-pressed walnut oils under accelerated storage conditions. The oxidative stability of both oils was evaluated using physicochemical parameters: chemical composition (fatty acids, phytosterols, and tocopherols), pigment content (chlorophyll and carotenoids), specific extinction coefficients (K232 and K270), and quality indicators (acid and peroxide value) as well as the evaluation of radical scavenging activity by the DPPH method. The changes in these parameters were evaluated within 60 days at 60 ± 2 °C. The results showed that the levels of total phytosterols, the parameters of the acid and peroxide value, K232 and K270, increased slightly for both oils as well as the total tocopherol content and the antioxidant activity affected by the roasting process. In contrast, the fatty acid profiles did not change considerably during the 60 days of our study. After two months of oil treatment at 60 °C, the studied oils still showed an excellent physicochemical profile, which allows us to conclude that these oils are stable and can withstand such conditions. This may be due to the considerable content of tocopherols (vitamin E), which acts as an antioxidant.

Lipid Oxidation Changes of Arabica Green Coffee Beans during Accelerated Storage with Different Packaging Types.

The storage conditions of green coffee beans (GCBs) are indispensable in preserving their commercial value. In Thailand, coffee farmers and roasters typically store GCBs for six months to a year before roasting. However, the beans undergo oxidation during storage, influencing both quality and taste. This study investigated changes in GCB lipid oxidation under different accelerated storage conditions (30 °C, 40 °C and 50 °C with 50% RH) and packaging, i.e., plastic woven (PW), low-density polyethylene (LDPE) and hermetic/GrainPro® (GP) bags. Samples were collected every five days (0, 5, 10, 15 and 20 days) and analyzed for lipid oxidation parameters including acid value (AV), free fatty acids (FFA), peroxide value (PV), ρ-anisidine value (PAV), total oxidation value (TOTOX), thiobarbituric acid reactive substances (TBARS), moisture content (MC), water activity (aw) and color. Primary oxidation was observed, with AV, FFA and PAV gradually changing during storage from 1.49 ± 0.32 to 3.7 ± 0.83 mg KOH/g oil, 3.82 ± 0.83 to 9.51 ± 1.09 mg KOH/g oil and 0.99 ± 0.03 to 1.79 ± 0.14, respectively. Secondary oxidation changes as PV and TBARS were reported at 0.86 ± 0.12 to 3.63 ± 0.10 meq/kg oil and 6.76 ± 2.27 to 35.26 ± 0.37 MDA/kg oil, respectively, affecting the flavor and odor of GCBs. Higher storage temperature significantly influenced a lower GCB quality. GP bags maintained higher GCB quality than LDPE and PW bags. Results provided scientific evidence of the packaging impact on oxidation for GCB under accelerated storage.

Enhancement of oxidative stability of soybean oil via nano-emulsification of eggplant peel extract: Process development and application

To extend the oxidative stability of soybean oil with encapsulated natural antioxidants, eggplant peel-based water-in-oil (W/O) nanoemulsions were formulated. The nanoemulsions were developed with eggplant peel extract (1000–9000 ppm) and CR-310 emulsifier (8–10 %) via ultrasonication. Seven W/O nanoemulsion formulations exhibited high sedimentation stability (sedimentation index > 92.58 %), a mean droplet diameter < 100 nm and low polydispersity index (<0.25) during 30 days storage. These nanoemulsions achieved controlled release of polyphenols. The low conjugated diene and p-anisidine value (Schaal oven parameters) of the nanoemulsions compared to pure soybean oil and commercial soybean oil suggested that these W/O nanoemulsions restricted oxidation better than these oils. Moreover, they could control the oxidation of soybean oil for approximately 10–15 days under accelerated storage conditions. Further, the induction period in Rancimat also indicated that the nanoemulsions possessed higher oxidative stability compared to pure soybean oil while three nanoemulsions even exhibited higher induction period than commercial soybean oil.

Content and stability of B complex vitamins in commercial cosmetic products.

Individual B vitamins have many favorable effects on the skin and are common cosmetic ingredients. However, their formulation is demanding due to stability issues, which consequently affect the products' quality. We aimed to determine the quality (labeling accuracy, content determination, and content-related quality control) and stability under long-term and accelerated storage conditions of a representative sample of commercial cosmetics containing the most common B vitamins - nicotinamide, dexpanthenol, pyridoxine, and cyanocobalamin. Cyanocobalamin was determined by a previously published stability-indicating HPLC- diode array detector (DAD) method for the simultaneous determination of all hydrophilic vitamins. This method was additionally simplified and adjusted for the time-effective analysis of nicotinamide, dexpanthenol, and pyridoxine. Both methods were properly validated. All labeled B vitamins were present in the 36 tested products, mostly in contents, reported effective on the skin. Thus, a straightforward correlation between vitamin contents and product prices were not observed. The content-related quality control of eight products, which quantitively specify their content, revealed significantly lower nicotinamide contents (47% and 57%) in two products and appropriate or higher nicotinamide (102%-112%) and dexpanthenol (100%-104%) contents than declared in the remaining products. The 6-month long-term and accelerated stability studies demonstrated the products' physical stability, but also revealed dexpanthenol, pyridoxine, and cyanocobalamin degradation, while nicotinamide was mostly stable in the tested products. The obtained results provide an inside into the quality of commercial vitamin B cosmetics and highlight the importance of stability testing in the formulation of quality, efficient, and safe cosmetics.

Development and characterization of active packaging films based on chitosan, plasticizer, and quercetin for repassed oil storage

Novel chitosan (Ch) films containing choline chloride and citric acid mixture as plasticizer (deep eutectic solvent, DES) and different amounts of quercetin (QUE) as antioxidant additive were prepared. Physicochemical and mechanical characteristics of the developed Ch/DES/QUE films were studied using FTIR, SEM, and AFM techniques. FTIR spectra revealed the possible interactions between all the components. The surface of the films was dense and rough. The addition of quercetin caused an increase in the tensile strength (TS) and Young's modulus, but significantly decreased the elongation at break. The films containing quercetin showed improved antioxidant activity in relation to Ch/DES film. Finally, the oxidation phenomena of rapeseed oils with and without chitosan films were evaluated as amounts of primary and secondary oxidation products and total oxidation index. The addition of Ch/DES films with quercetin to oil samples successfully retarded secondary lipid oxidation processes and improved its antioxidant activity under the accelerated storage condition.

Computational design of a chitosan derivative for improving the color stability of anthocyanins: Theoretical calculation and experimental verification

The objective of this study was to design a chitosan (CS) derivative with good protective effect on the color stability of anthocyanins (ACNs) under accelerated storage. The binding affinities and interactions of 12 organic acids with cyanidin-3-O-glucoside (C3G) were evaluated using quantum mechanics method. Sinapic acid (SinA) showing the strongest interaction with C3G was selected for the synthesis of SinA-grafted-CS (SinA-g-CS), which was further characterized by FTIR and 1H NMR. Under accelerated storage conditions (40 °C), SinA-g-CS significantly improved the color stability of black rice anthocyanins (BRA) in the presence of l-ascorbic acid (pH 3.0), and showed a better protective effect than that of CS. Moreover, molecular dynamics simulation analysis showed SinA-g-CS formed more hydrogen bonds with C3G than CS. Our study demonstrated that SinA-g-CS designed by computational methods can effectively protect ACNs from degradation, and has the potential to be used in ACN-rich beverages as a replacement for CS.

Nanoemulsification of Kaempferia galanga essential oil: Characterizations and molecular interactions explaining fungal growth suppression

Present study envisaged the development of nanoemulsions (NEs) based on essential oil (EO) of Kaempferia galanga using biosurfactant, saponin. Aromatic components of the distilled EO were characterized in GC-MS and the oil was formulated to prepare NEs with saponin at three different concentrations (0.5%, 1.0% and 2.0%) using ultrasonic acoustic energy at three individual time points (3, 5 and 10 min). NEs prepared with ≥ 1% saponin solution with ≥ 10 min ultrasonication were found stable even after accelerated storage condition at 54 ± 1 °C for 14 days. Briefly, NEs at 400 µg/mL concentration, showed hydrodynamic droplet diameter of 71.68 nm with the corresponding PDI 0.52 and zeta potential − 20.05 mV. TEM images confirmed the spherical morphology and droplet diameters. NEs exhibited excellent efficacy against A. flavus 2547 (32.3 µg/mL) followed by A. flavus 2838 (45.6 µg/mL), A. flavus 8601 (56.2 µg/mL) and A. flavus 6641 (69.7 µg/mL). Molecular modelling studies revealed the most promising binding complexes of 6IV7-ethyl-p-methoxycinnamate (−56.22 kcal/mol), the key component responsible for interfering functional properties of the native ligand. Additive interaction effect of 4QBJ-pentadecane (−50.15 kcal/mol) and 6JOH-ethyl-p-methoxycinnamate (−45.91 kcal/mol) attributed to the extraordinary favourable binding energy for non-bonded covalent and lipophilic interactions towards the selective target proteins.

Design of Ternary Amorphous Solid Dispersions for Enhanced Dissolution of Drug Combinations.

Using sulfamethoxazole (SMZ) and trimethoprim (TMP) as model drugs, we designed amorphous solid dispersions (ASDs) for the simultaneous solubility enhancement of two active pharmaceutical ingredients (APIs) by exploiting the drug-drug and drug-polymer interactions. In order to make this approach broadly applicable and over a wide dose range, a mixture of SMZ and TMP at weight ratios of 5:1 and 1:5 (w/w) were formulated into ternary ASDs. Depending on the dose ratio of the two drugs, the polymer used was either an aminoalkyl methacrylate copolymer (Eudragit, EDE) or polyacrylic acid. The drug-drug and drug-polymer interactions were characterized to be ionic by infrared and solid-state nuclear magnetic resonance spectroscopy. The interactions resulted in a substantial reduction in molecular mobility, evident from the increase in the structural relaxation time determined by dielectric spectroscopy. The drug-drug interaction resulted in ∼3 orders of magnitude reduction in molecular mobility. The addition of a polymer led to a further decrease in molecular mobility of up to 4 orders of magnitude. The strength of intermolecular interactions was also estimated from the glass transition temperatures of the ASDs obtained by differential scanning calorimetry. The strong intermolecular interactions yielded highly stable ASDs with no evidence of crystallization, both at elevated temperatures and under accelerated storage conditions (40 °C/75% relative humidity; 6 weeks). The dissolution performances of the ASDs were evaluated using the area under the curve (AUC) obtained from the concentration-time profiles under the non-sink condition. SMZ and TMP in their ternary ASDs, when compared with their crystalline counterparts, exhibited up to 6.4- and 4.6-fold increases in AUC, respectively. Importantly, the synchronized release of the two drugs was observed, a desirable attribute in synergistic formulations. A single-phase ternary ASD, stabilized by drug-drug and drug-polymer interactions, is likely responsible for the unique release profile.

Individual and Joint Effect of Alpha-Tocopherol and Hydroxytyrosol Acetate on the Oxidation of Sunflower Oil Submitted to Oxidative Conditions: A Study by Proton Nuclear Magnetic Resonance.

This study tackles the individual and joint effect of alpha-tocopherol and hydroxytyrosol acetate on the oxidation of sunflower oil submitted to accelerated storage conditions at intermediate temperature, in order to deepen the understanding of antioxidant–prooxidant behaviour. This was accomplished by 1H Nuclear Magnetic Resonance. For this purpose, the evolution of the degradation of both the main components of the oil and the aforementioned added compounds was monitored by this technique throughout the storage time. Furthermore, the formation of a very large number of oxylipins and the evolution of their concentration up to a very advanced stage of oil oxidation, as well as the occurrence of lipolysis, were also simultaneously studied. The results obtained show very clearly and thoroughly that in the oxidation process of the oil enriched in binary mixtures, interactions occur between alpha-tocopherol and hydroxytyrosol acetate that notably reduce the antioxidant effect of the latter compound with the corresponding negative consequences that this entails. The methodology used here has proved to be very efficient to evaluate the antioxidant power of mixtures of compounds.

Dual Functionality of Bile Acid: Physical Stabilization of Drugs in the Amorphous Form and Solubility Enhancement in Solution.

Drugs containing an amino aromatic nitrogen moiety were stabilized in the amorphous form by the surfactant cholic acid (CA). Coamorphous systems of lamotrigine (LAM), pyrimethamine (PYR), and trimethoprim (TRI) were each prepared with CA. Drug-CA interactions, investigated by IR and solid-sate NMR spectroscopy, revealed deprotonation of the carboxylic acid group in CA and the protonation of the most basic nitrogen of the drug. The coamorphous systems exhibited exceptional physical stability and resisted crystallization at (i) elevated temperatures (>100 °C) and (ii) accelerated storage conditions, 40 °C/75% relative humidity for 15 months. The dissolution performance of each coamorphous system was compared with the respective crystalline drug based on the area under the curve (AUC) of the concentration-time profiles. A 25-fold increase in AUC was observed in the PYR-CA coamorphous system. The solubility enhancement is attributed not only due to drug amorphization but also due to solubilization by CA. The supramolecular synthon approach, through a drug-CA interaction, yielded physically stable coamorphous systems with enhanced aqueous drug solubility.