Accelerated Storage Conditions Research Articles

Stability of furosemide polymorphs and the effects of complex formation with β-cyclodextrin and maltodextrin

The effect of the formation of supramolecular binary complexes with β-cyclodextrin and maltodextrin on the chemical and physical stability of the polymorphs I and II of furosemide was evaluated in solid state. The solid samples were placed under accelerated storage conditions and exposed to daylight into a stability chamber for a 6-month. Chemical stability was monitored by high performance liquid chromatography, while the physical stability was studied by solid state nuclear magnetic resonance, powder X-ray diffraction and scanning electron microscopy. Changes in the physical appearance of the samples were evaluated. The studies showed a significant stabilizing effect of β-cyclodextrin on furosemide form II. Our results suggest that the complex formation is a useful tool for improving the stability of furosemide polymorphs. These new complexes are promising candidates that can be used in the pharmaceutical industry for the preparation of alternative matrices that improve physicochemical properties

Effect of Storage Conditions and Packaging Materials on Quality Parameters of Curcuminoids Impregnated Coconut and Raw Banana Slices

Effect of storage conditions and packaging materials on quality parameters of curcuminoids infused coconut and raw banana slices were studied. Moisture sorption study was conducted for the developed products in selected packaging materials namely polypropylene (PP), polyethylene terephthalate (PET)/low density polyethylene terephthalate (LDPE) and metallized PET/LDPE, under ambient and accelerated storage conditions for 90 days. The changes in physical, chemical and sensory parameters of the products were studied during the storage period. The results indicated that 40% relative humidity was critical for storage of products, above which the products required a good moisture barrier to achieve the enhanced shelf-life of the products. In accelerated storage conditions, the moisture content exceeded the critical moisture content for coconut and raw banana slices within 30 days and 15 days, respectively leading to product deterioration. At the end of the storage period the coconut samples packed in PP and PET/LDPE crossed the critical moisture content (3.05%) at ambient storage conditions, whereas, the moisture content of raw banana samples was within the moisture tolerance limit (11.5%). The curcuminoids retention, chroma and total color difference (DE) were significantly higher with better sensory attributes for products packed in metallized PET/LDPE compared to PET/LDPE and PP. Among all the packaging materials studied metallized PET/LDPE was found to be a suitable packaging material for both products. PRACTICAL APPLICATIONS The present work deals with the effect of packaging material on physical, chemical and sensory parameters on the products (curcuminoids impregnated coconut and raw banana slices) infused with bioactive compounds. The study reveals the criteria for the selection of packaging materials as well as storage conditions for curcuminoids impregnated coconut and raw banana slices for the higher retention of bioactive compounds, besides fulfilling consumer desire, satisfying industry requirement and maintaining food safety.

Risk/benefit considerations of a new formulation of wheat-based biscuit supplemented with different amounts of chia flour

The incorporation of Chia (Salvia hispanica L.) in the formulation of certain foods may be particularly desirable from a nutritional and healthy point of view. The effect of addition of chia flour on the nutritional properties and the formation of process contaminants in wheat flour-based biscuits was investigated. Higher percentage of chia flour in the formula increased the antioxidant capacity, phenolic compounds, protein, fiber and polyunsaturated fatty acids content, then resulting in a nutritionally enhanced product. However levels of process contaminants were also increased and thus acrylamide, hydroxymethylfurfural and furfural ranged between 151 and 1188 μg/kg, 22.8–71.4 mg/kg and 1.3–5.6 mg/kg, respectively, when chia was added in a range of 0–20% of the total weight. In parallel, the formation of dicarbonyl compounds, such as methylglyoxal and glyoxal, were significantly increased with addition of 5%. Lipid oxidation, particularly polymerization compounds, was accelerated in chia-enriched biscuits, which decreased the shelf-life of the product by promoting a rapid rancidity under accelerated storage conditions. Therefore, although nutritional properties are improved by the incorporation of chia into the biscuits, the increase in the content of process contaminants and the extent of the lipid oxidation should be carefully considered in a context of risk/benefit.

Toward determining fat quality parameters of fish oil by means of 1H NMR spectroscopy

The consumption of fish oil‐based dietary supplements has increased dramatically in recent years, which is mainly due to their high content of health promoting omega‐3 fatty acids. However, these polyunsaturated fatty acids are extremely prone to oxidation. This study investigated the potential of 1H NMR spectroscopy for the assessment of the oxidative deterioration of fish oils. Nine raw fish oils of different fish species were stored for 3 months at room temperature at different degrees of sunlight exposure as well as under standardized accelerated storage conditions for 6 days (at 40°C and under constant light exposure). Fish oil samples were analyzed by 1H NMR spectroscopy as well as by traditional methods to determine the fat quality parameters peroxide value (PV), anisidine value (AnV), TOTOX value, and acid value (AV). PLS (partial least squares) regression models were used to predict these fat quality parameters based on the 1H NMR spectra. The best regression models reached an R2 of 0.949, 0.962, 0.991, and 0.977 for PV, AnV, TOTOX value, and AV, respectively. In conclusion, 1H NMR spectroscopy is a promising approach for a fast, reliable, and sustainable assessment of fish oil quality with regard to lipid oxidation.Practical applications: The results indicate a great potential of 1H NMR spectroscopy in the quality assessment of fish oils. This technology requires little time, work, amount of sample, and solvent and provides extensive information that can be obtained from a single spectrum. Such an approach is significantly more specific and detailed than traditional lipid oxidation parameters.Nine raw fish oils are stored under different conditions and analyzed by 1H NMR spectroscopy as well as by traditional methods to determine the lipid quality parameters peroxide value, anisidine value, TOTOX value, and acid value. Subsequently, PLS regression models are generated to predict these indices from the NMR spectra.

Abstracts from The Aerosol Society Drug Delivery to the Lungs 26 Edinburgh International Conference Centre Edinburgh, Scotland, UK December 9-11, 2015.

Abstracts from The Aerosol Society Drug Delivery to the Lungs 26 Edinburgh International Conference Centre Edinburgh, Scotland, UK December 9-11, 2015.

Microencapsulation of chlorthalidone by spray-drying of double emulsion and melt granulation coating

ABSTRACTChlorthalidone (CH) is indicated in the management of hypertension either alone or in combination with other antihypertensive drugs, but it displays poor solubility and stability limiting its use in the development of new pharmaceutical alternatives. Spray-drying of double emulsions (SDE) and melt granulation coating (MGC) technologies were used for enhancing the stability of CH by using Eudragit® L30D-55 (EUD), Opadry® II (OPA), or Kollicoat® IR (KIR) as wall materials. SDE and MGC microcapsules containing CH were evaluated for particle size, morphology, release profiles, accelerated storage, and thermo-oxidative stability. Both types of microcapsules showed higher solubility (>80% in 20 min), lower degradation (<2%) under accelerated storage condition, and lower thermo-oxidative degradation than pure CH. However, SDE microcapsules showed smaller particle sizes (<16 µm) than MGC microcapsules (>700 µm), which widens the opportunity of incorporating microcapsules to dosage forms requiring different particle sizes for achieving their functionality.

Study of sorption behavior, shelf life and colour kinetics of vacuum puffed honey powder at accelerated storage conditions.

In the study, the storage life of vacuum puffed honey powder at accelerated storage environment (90% relative humidity and 36°C) was computed by determining the sticky-point moisture content as the critical parameter of the honey powder. The value of monolayer moisture content in the GAB model was calculated to be 0.081kg water/kg dry solids by fitting water activity and moisture sorption data. Shelf life of the honey powder was predicted to be 222days when the powder was packaged in aluminum foil-laminated polyethylene pouches with permeability value of 5.427X10(-8)kg/m(2)//day/Pa. Actual shelf life of honey powder was experimentally determined as 189days and analysis of mean relative percent derivation modulus (Rd) and root mean square (RMS) established the accuracy and acceptability of the technique for the prediction of shelf life of honey powder. Overall colour deviation pattern followed first order reaction kinetics with rate constant (k1) as 0.037day(-1). This study revealed overall colour difference of 18.1 till the end of shelf life with drastic change during initial storage period.

Preparation and characterizations of stable amorphous solid solution of azithromycin by hot melt extrusion

In the present study aim was to prepare stable solid solution azithromycin dihydrate (AZI) by hot melt extrusion technology (HME). Soluplus and Kollidon® VA 64 were selected among polymers based on Hansen solubility parameter calculation in order to prepare amorphous of AZI. Further physicochemical properties of extrudates were characterized by DSC, FTIR, XRD, SEM and contact angle measurement. DSC revealed single broad endothermic peak in extrudates indicated miscibility of AZI into polymeric carriers, which formed monophasic solid system termed as solid solution. XRD confirmed amorphous nature of AZI in extrudates. DSC and XRD suggested molecular dispersion of AZI in polymeric carriers. Amorphous AZI exhibited statistically significant high solubility (P < 0.0001) in water in comparison with pure AZI. Solid solution batch AZI 03 showed significant enhancement in solubility (P = 0.0004) in pH 6. The dissolution in dissolution medium pH 6 and water resulted in statistically significant differences (P < 0.05) in the percentage amorphous AZI dissolved compared to the percentage AZI dissolved over the period of 60 min. Solid solution formulation showed better wettability than that of pure AZI. Amorphization and increased wettability attributed to solubility and dissolution rate enhancement. Assay and amorphous solid solution characteristics of AZI were found to be stable under accelerated storage condition as per ICH guideline for a period of six months. Therefore, hot melt extrusion technology was suitable method to prepare stable solid solution and dissolution rate enhancement for poorly soluble active like AZI.

Spectroscopic evaluation of a freeze-dried vaccine during an accelerated stability study

This research evaluates a freeze-dried live, attenuated virus vaccine during an accelerated stability study using Near Infrared (NIR) and Fourier Transform Infrared (FTIR) spectroscopy in addition to the traditional quality tests (i.e., potency assay and residual moisture analysis) and Modulated Differential Scanning Calorimetry (MDSC). Therefore, freeze-dried live, attenuated virus vaccines were stored during four weeks at 4°C (i.e., recommended storage condition) and at 37°C (i.e., accelerated storage condition) and weekly analyzed using these techniques. The potency assay showed that the virus titer decreased in two phases when the samples were stored at 37°C. The highest titer loss occurred during the first week storage at 37°C after which the degradation rate decreased. Both the residual moisture content and the relaxation enthalpy also increased according to this two-phase pattern during storage at 37°C. In order to evaluate the virus and its interaction with the amorphous stabilizer in the formulation (trehalose), the NIR spectra were analyzed via principal component analysis (PCA) using the amide A/II band (5029–4690cm−1). The FTIR spectra were also analyzed via PCA using the amide III spectral range (1350–1200cm−1). Analysis of the amide A/II band in the NIR spectra revealed that the titer decrease during storage was probably linked to a change of the hydrogen bonds (i.e., interaction) between the virus proteins and the amorphous trehalose. Analyzing the amide III band (FTIR spectra) showed that the virus destabilization was coupled to a decrease of the coated proteins β turn and an increase of α helix. During storage at 4°C, the titer remained constant, no enthalpic relaxation was observed and neither the Amide A/II band (NIR spectra) nor the Amide III band (FTIR spectra) varied.

“Influence of storage conditions on phenolic compounds stability, antioxidant capacity and colour of freeze-dried encapsulated red wine”

A concentration of 9% (w/w) maltodextrin (DE 10) and gum arabic was added to red wine C. sauvignon and freeze dried to obtain a dealcoholized wine powder having a polyphenols concentration 7.1 times higher than in liquid red wine. Malvidin 3-G and total anthocyanins were the phenolics showing greater losses during storage. Moreover, an increase of water activity from 0.11 to 0.58 greatly enhanced the losses. The decrease in malvidin 3-G content was associated with the decrease on redness (colour parameter a*) of wine powder. Gallic acid was the most stable phenolic and its content remained constant during storage at all water activity levels under investigation. Contents of epicatechine, catechine, caffeic acid and resveratrol remained constant at aw = 0.11, although at aw = 0.33 catechine and epicatechine suffered important losses. Results indicated that water activity was a key factor affecting phenolics stability during storage.Antioxidant activity of the wine powder remained constant over 145 days at accelerated storage conditions.

Piperine containing floating microspheres: an approach for drug targeting to the upper gastrointestinal tract.

The purpose of this investigation was to prepare and characterize acyclovir loaded floating microspheres by emulsification solvent evaporation method. Piperine was added to investigate its effect on acyclovir bioavailability. The microspheres were characterized for size, shape, entrapment efficiency, in vitro drug release, and in vivo pharmacokinetic parameters. The morphological characterization of microspheres was done using a scanning electron microscope. The microspheres were spherical and had particle size in the range of 400 to 525μm. The percent drug entrapment efficiency varied between 56.12 ± 1.32% to 87.32 ± 5.28%. The drug release was decreased at higher polymer concentrations. Nearly two times higher AUC0-24 value of acyclovir-loaded piperine containing microspheres (15614.13 ± 6953.13nghml(-1)) was observed as compared to the drug solution (7552.33 ± 3219.09nghml(-1)). Under the accelerated storage conditions, the best selected formulation was found to be stable for 90days. The preliminary results of this study suggest that the developed microspheres containing acyclovir could enhance drug entrapment efficiency, reduce initial burst release, and prolong the drug release with enhanced bioavailability.

Formulation, physicochemical characterization and stability study of lithium-loaded microemulsion system

Lithium biocompatible microemulsion based on Peceol®, lecithin, ethanol and water was studied in attempt to identify the optimal compositions in term of drug content, physicochemical properties and stability. Lithium solubilization in microemulsion was found to be compatible with a drug-surfactant binding model. Lithium ions were predominantly solubilized within lecithin head group altering significantly the interfacial properties of the system. Pseudo-ternary phase diagrams of drug free and drug loaded microemulsions were built at constant ethanol/lecithin weight ratio (40/60). Lithium loaded microemulsion has totally disappeared in the Peceol® rich part of phase diagram; critical fractions of lecithin and ethanol were required for the formation of stable microemulsion. The effect of lithium concentration on the properties and physical stability of microemulsions were studied using microscopy, Karl Fischer titrations, rheology analyses, conductivity measurements and centrifugation tests. The investigated microemulsions were found to be stable under accelerated storage conditions. The systems exhibited low viscosity and behaved as Newtonian fluid and no structural transition was shown.

Electrophilic Oxidation and [1,2]-Rearrangement of the Biindole Core of Birinapant.

Birinapant/TL32711 (1) is a bivalent antagonist of the inhibitor of apoptosis (IAP) family of proteins and was designed to mimic AVPI, the N-terminal tetrapeptide of the second mitochondria-derived activator of caspases (Smac/DIABLO). Birinapant bound to the BIR3 domains of cIAP1, cIAP2, and XIAP with K i values of 1, 36, and 45 nM, respectively. Birinapant-mediated activation of cIAP1 resulted in cIAP1 autoubiquitylation and degradation and correlated with inhibition of TNF-mediated NF-κB activation, induction of tumor cell death in vitro, and tumor regression in vivo. Birinapant is being evaluated in Phase 1/2 trials for the treatment of cancer and hepatitis B virus (HBV) infection. After one year at accelerated storage conditions, a formulation of 1 afforded four degradants in >0.1% abundance by HPLC analysis. The primary degradants (2 and 3) were formed via oxidation of the biindole core, while the secondary degradants (5 and 6) arose via [1,2]-rearrangement of 3 and 2, respectively. Forced degradation conditions were developed, which allowed the isolation of 2 and 3 in multigram quantities. Novel deuterated analogues of 1 were prepared to determine the site of oxidation, and NMR experiments confirmed the chemical structures of 5 and 6. The de novo synthesis of 2, 3, 5, and 6 confirmed these experimental findings.

Comparative Stability of Egg Snack Fried in Rice Bran Oil and Sunflower Oil under Accelerated Storage Conditions

Comparative Stability of Egg Snack Fried in Rice Bran Oil and Sunflower Oil under Accelerated Storage Conditions

Physical and oxidative stability of functional olive oil-in-water emulsions formulated using olive mill wastewater biophenols and whey proteins.

The present paper reports on the use of phenolic extracts from olive mill wastewater (OMW) in model olive oil-in-water (O/W) emulsions to study their effect on their physical and chemical stability. Spray-dried OMW polyphenols were added to a model 20% olive O/W emulsion stabilized with whey protein isolate (WPI) and xanthan gum, in phosphate buffer solution at pH 7. The emulsions were characterised under accelerated storage conditions (40 °C) up to 30 days. Physical stability was evaluated by analysing the creaming rate, mean particle size distribution and mean droplet size, viscosity and rheological properties, while chemical stability was assessed through the measurement of primary and secondary oxidation products. The rheological behaviour and creaming stability of the emulsions were dramatically improved by using xanthan gum, whereas the concentration of WPI and the addition of encapsulated OMW phenolics did not result in a significant improvement of physical stability. The formation of oxidation products was higher when higher concentrations of encapsulated polyphenols were used, indicating a possible binding with the WPI added in the system as a natural emulsifier. This paper might help in solving the issue of using the olive mill wastewater from olive processing in formulating functional food products with high antioxidant activity and improved health properties.

Acid-Base Interactions of Polystyrene Sulfonic Acid in Amorphous Solid Dispersions Using a Combined UV/FTIR/XPS/ssNMR Study.

This study investigates the potential drug-excipient interactions of polystyrene sulfonic acid (PSSA) and two weakly basic anticancer drugs, lapatinib (LB) and gefitinib (GB), in amorphous solid dispersions. Based on the strong acidity of the sulfonic acid functional group, PSSA was hypothesized to exhibit specific intermolecular acid-base interactions with both model basic drugs. Ultraviolet (UV) spectroscopy identified red shifts, which correlated well with the color change observed in lapatinib-PSSA solutions. Fourier transform infrared (FTIR) spectra suggest the protonation of the quinazoline nitrogen atom in both model compounds, which agrees well with data from the crystalline ditosylate salt of lapatinib. X-ray photoelectron spectroscopy (XPS) detected increases in binding energy of the basic nitrogen atoms in both lapatinib and gefitinib, strongly indicating protonation of these nitrogen atoms. (15)N solid-state NMR spectroscopy provided direct spectroscopic evidence for protonation of the quinazoline nitrogen atoms in both LB and GB, as well as the secondary amine nitrogen atom in LB and the tertiary amine nitrogen atom in GB. The observed chemical shifts in the LB-PSSA (15)N spectrum also agree very well with the lapatinib ditosylate salt where proton transfer is known. Additionally, the dissolution and physical stability behaviors of both amorphous solid dispersions were examined. PSSA was found to significantly improve the dissolution of LB and GB and effectively inhibit the crystallization of LB and GB under accelerated storage conditions due to the beneficial strong intermolecular acid-base interaction between the sulfonic acid groups and basic nitrogen centers.

Thermoanalytical and Fourier transform infrared spectral curve-fitting techniques used to investigate the amorphous indomethacin formation and its physical stability in Indomethacin-Soluplus® solid dispersions

The amorphous form of a drug has higher water solubility and faster dissolution rate than its crystalline form. However, the amorphous form is less thermodynamically stable and may recrystallize during manufacturing and storage. Maintaining the amorphous state of drug in a solid dosage form is extremely important to ensure product quality. The purpose of this study was to quantitatively determine the amount of amorphous indomethacin (INDO) formed in the Soluplus® solid dispersions using thermoanalytical and Fourier transform infrared (FTIR) spectral curve-fitting techniques. The INDO/Soluplus® solid dispersions with various weight ratios of both components were prepared by air-drying and heat-drying processes. A predominate IR peak at 1683cm−1 for amorphous INDO was selected as a marker for monitoring the solid state of INDO in the INDO/Soluplus® solid dispersions. The physical stability of amorphous INDO in the INDO/Soluplus® solid dispersions prepared by both drying processes was also studied under accelerated conditions. A typical endothermic peak at 161°C for γ-form of INDO (γ-INDO) disappeared from all the differential scanning calorimetry (DSC) curves of INDO/Soluplus® solid dispersions, suggesting the amorphization of INDO caused by Soluplus® after drying. In addition, two unique IR peaks at 1682 (1681) and 1593 (1591)cm−1 corresponded to the amorphous form of INDO were observed in the FTIR spectra of all the INDO/Soluplus® solid dispersions. The quantitative amounts of amorphous INDO formed in all the INDO/Soluplus® solid dispersions were increased with the increase of γ-INDO loaded into the INDO/Soluplus® solid dispersions by applying curve-fitting technique. However, the intermolecular hydrogen bonding interaction between Soluplus® and INDO were only observed in the samples prepared by heat-drying process, due to a marked spectral shift from 1636 to 1628cm−1 in the INDO/Soluplus® solid dispersions. The INDO/Soluplus® solid dispersions prepared by both drying processes could keep the amorphous state of INDO in the INDO/Soluplus® solid dispersions at the accelerated storage condition.

The oxidative stability of synthetic fuels and fuel blends with monoaromatic blending components

Alternative jet fuels and blends are required to meet a minimum aromatic concentration of 8%. It has been proposed that some monoaromatic compounds may make suitable single component aromatics to meet this minimum. One monoaromatic of interest is p-cymene which can be efficiently produced from eucalyptus oil. The oxidative stability of p-cymene and a range of monoaromatics blended with a range of alternative fuels are examined. Their oxygen induction times and peroxide formation under accelerated storage conditions are reported. It was found that some monoaromatics can impact final blend stability and that p-cymene produces very high levels of peroxides with all fuels examined. It was also observed that the choice of conventional fuel used for blending also influenced the blend stability.

Co-Amorphous Combination of Nateglinide-Metformin Hydrochloride for Dissolution Enhancement.

The aim of the present work was to prepare a co-amorphous mixture (COAM) of Nateglinide and Metformin hydrochloride to enhance the dissolution rate of poorly soluble Nateglinide. Nateglinide (120mg) and Metformin hydrochloride (500mg) COAM, as a dose ratio, were prepared by ball-milling technique. COAMs were characterized for saturation solubility, amorphism and physicochemical interactions (X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR)), SEM, in vitro dissolution, and stability studies. Solubility studies revealed a sevenfold rise in solubility of Nateglinide from 0.061 to 0.423mg/ml in dose ratio of COAM. Solid-state characterization of COAM suggested amorphization of Nateglinide after 6h of ball milling. XRPD and DSC studies confirmed amorphism in Nateglinide, whereas FTIR elucidated hydrogen interactions (proton exchange between Nateglinide and Metformin hydrochloride). Interestingly, due to low energy of fusion, Nateglinide was completely amorphized and stabilized by Metformin hydrochloride. Consequently, in vitro drug release showed significant increase in dissolution of Nateglinide in COAM, irrespective of dissolution medium. However, little change was observed in the solubility and dissolution profile of Metformin hydrochloride, revealing small change in its crystallinity. Stability data indicated no traces of devitrification in XRPD of stability sample of COAM, and % drug release remained unaffected at accelerated storage conditions. Amorphism of Nateglinide, proton exchange with Metformin hydrochloride, and stabilization of its amorphous form have been noted in ball-milled COAM of Nateglinide-Metformin hydrochloride, revealing enhanced dissolution of Nateglinide. Thus, COAM of Nateglinide-Metformin hydrochloride system is a promising approach for combination therapy in diabetic patients.

Antioxidant efficacy of mangosteen (Garcinia mangostana Linn.) peel extracts in sunflower oil during accelerated storage

Abstract This study evaluated the efficacy of mangosteen peel extracts (100 and 200 ppm) in stabilizing sunflower oil tested under accelerated storage (65 °C) for a period of 24 days. BHA and α-tocopherol were used as comparative standards besides the control. Established parameters such as peroxide value (PV), iodine value (IV), p -anisidine value ( p -AnV), total oxidation value (TOTOX), thiobarbituric acid reactive substances (TBARS) and free fatty acid (FFA) content were used to assess the extent of oil deterioration. After 24 days storage at 65 °C, sunflower oil containing 200 ppm extract of mangosteen peel showed significant lower PV and TOTOX compared to BHA and α-tocopherol. TBARS, p -AnV and FFA values of sunflower oil containing 200 ppm of mangosteen peel extract exhibited comparable inhibitory effects with BHA. Mangosteen peel extract at 200 ppm exhibited inhibitory effect against both primary and secondary oxidation up to 24 days under accelerated storage conditions. Thus, it is suggested that mangosteen peel extract may be used as a potential source of natural antioxidants in the application of food industry to suppress lipid oxidation.