Physico-chemical characterization and stability study of glassy simvastatin

The objective of the present study was to investigate the glass forming capability of a model drug simvastatin. The glassy material produced by melt quench technique was subjected to physico-chemical characterization and subsequent stability and enthalpy relaxation study. The chemical stability of drug during preparation of glass was tested by High Performance Liquid Chromatography (HPLC) and Infrared (IR) spectroscopy. The presence of amorphous form was confirmed by DSC and XRPD. Surprisingly, glassy simvastatin was almost stable throughout the period of stability, inspite of its T_g being relatively low. The stability and very low enthalpy recovery of glassy simvastatin perhaps could be attributed to strong inter-molecular hydrogen bonding.     

Stability of the structure corresponding to the prepeak and amorphous Al90Tm5Ce5 alloys

The stability of amorphous Al₉₀Fe₅Ce₅ and Al₉₀Ni₅Ce₅ alloys and the stability of the structure corresponding to the prepeak during annealing process were investigated. Also the ageing effects of these alloys were investigated. Both the amorphous Al₉₀Fe₅Ce₅ and Al₉₀Ni₅Ce₅ alloys crystallize by two stages. The crystallization onset temperature for amorphous Al₉₀Fe₅Ce₅ alloys is much higher than that of the amorphous Al₉₀Ni₅Ce₅ alloys. The structure corresponding to the prepeak for amorphous Al₉₀Fe₅Ce₅ alloys is stable. However, it is not stable for amorphous Al₉₀Ni₅Ce₅ alloys, even decomposes at room temperature. By ageing effects, fcc Al is easily precipitated from amorphous matrix for the amorphous Al₉₀Ni₅Ce₅ alloys, whereas the amorphous Al₉₀Fe₅Ce₅ alloys is stable at room temperature. The stability of the structure corresponding to the prepeak strongly relates to the stability of the amorphous alloys.     

Preparation and Characterization of Glassy Celecoxib

Abstract

Celecoxib, a poorly water-soluble drug, was converted into a glassy state by melt quenching. The properties of glassy celecoxib were studied using infrared (IR) spectroscopy, differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), intrinsic dissolution rate (IDR), and thin-layer-chromatography (TLC). Glass transition occurred at 51.8°C. Infrared spectrum of glass has revealed significant changes due to H-bonding. Celecoxib glass shows around 15 times faster dissolution as compared with the crystalline state. Heckel plot analysis has shown better compressibility in glassy state. Unpulverized glass remained stable for 3 months, whereas after pulverization about 70% crystallinity was gained in 100 hours. Further attempts may be carried out to stabilize the glass.     

Preparation,characterization, stability and in vitro-in vivo evaluation of pellet-layered Simvastatin nanosuspensions

The objective of the present study was to develop stable pellets-layered Simvastatin (SIM) nanosuspensions with improved dissolution and bioavailability. The nanosuspensions were prepared with 7% HPMC, antioxidant 0.03% butylated hydroxyanisole and 0.2% citric acid (m/v) by low temperature grinding. After that, SDS with SIM was in a ratio of 1:5 (m/m), was evenly dispersed in the nanosuspensions. Then, they were layered on the surface of sugar pellets. The mean particle size of the SIM nanosuspensions was 0.74 µm, and 80.6% of the particles was below 1 µm in size. The pellets could re-disperse into nanoparticle status in the dissolution medium. In 900?mL pH 7.0 phosphate solutions, the dissolution of the layered pellets was better than that of commercial tablets. Also, nearly 100% of the drug dissolved from the pellets within 5?min under sink conditions. During the stability studies, SIM pellets exhibited good physical and chemical stability. The relative bioavailability of SIM and Simvastatin β-hydroxy acid (SIMA) for nanosuspensions layered pellets compared with commercial tablets was 117% and 173%, respectively. The bioavailability of SIMA was improved significantly (p < 0.05), confirming the improvement of bioavailability. Thus, the present study demonstrates that the pellet-layered SIM nanosuspensions improved both the dissolution and bioavailability of SIM.     

马铃薯淀粉粘合剂稳定性的探讨

马铃薯淀粉为原料,通过双氧水氧化制成氧化淀粉粘合剂,对不同贮存条件下氧化马铃薯淀粉粘合剂的物理化学性能进行研究,分析其变质机理.由此得出氧气存在下的氧化交联导致产品结皮,致使稳定性下降的结论.     

Design and In Vitro Evaluation of Polymeric Formulae of Simvastatin for Local Bone Induction

ABSTRACT

Simvastatin (SVS), a cholesterol-lowering drug, has been shown to stimulate bone formation. This study deals with the design and in vitro evaluation of local delivery systems for simvastatin. They are intended to treat bony defects resulting from periodontitis or to induce osteogenesis around the titanium implants. Granules and gels were formulated using bioerodible/biocompatible polymers, namely hydroxypropylmethyl cellulose (H), sodium carboxymethyl cellulose (C), and chitosan (Ch). The in vitro release profiles and kinetics were evaluated and the swelling and/or erosion was monitored. Differential scanning calorimetry (DSC) and infrared (IR) were used to detect any SVS/polymer interactions that may affect drug release. The results revealed variable extents of controlled drug release from the designed formulae depending on the polymer nature. About 50% cumulative SVS was released from both H granules and gel formulae within 24 h and ～66% and ～88% from C granules and gel, respectively. Ch formulae exhibited ～50% release from granules and ～30% from gel.     

安钢钢渣的路用稳定性研究

在道路建筑工程中,要想使用钢渣代替建筑用石料,钢渣的物理化学性质就必须符合道路工程的各项使用要求。本文采用国家规范的路用石料标准试验方法,对安钢钢渣进行测试,将测试结果与路用石料标准进行对比,并据此分析安钢钢渣的路用稳定性。     

A Stability Study of Ticlopidine Products from 18 Countries

The results of the stability study of ticlopidine formulations (250 mg and 100 mg) show that products available in many countries worldwide exhibit different stability characteristics. Stability testing under the International Conference on Harmonisation (ICH) accelerated test conditions (40°C/75% relative humidity [RH], 3 and 6 months) was performed on a total of 43 products obtained from 18 countries. The samples were visually examined for physical change and analyzed for their content of degradation products, remaining ticlopidine, and in vitro dissolution characteristics (in the case of tablets). Only 6 (16%) of all the samples submitted to this study had a good stability profile. Their appearance remained unchanged during the study; assay results were between 95% and 100%; their impurity content did not exceed 0.25%; and in the dissolution test, at least 75% of ticlopidine was dissolved after 30 min. Three samples had excellent dissolution properties and showed a very high purity level (viz. 21, 40, and 43) over the course of the study.     

Bioanalytical method development and its application to pharmacokinetics studies on Simvastatin in the presence of piperine and two of its synthetic derivatives

Piperine has been widely used as a bioenhancer. Simvastatin belongs to a group of medicines known as statins. It acts by inhibiting HMG CoA reductase and acts primarily as a hypolipidemic agent. In this study some derivatives of Piperine were synthesized. They were studied for their bioenhencing effect (10?mg kg^?1) and this effect was compared with that of Piperine. The pharmacokinectic profile of Simvastatin alone and in combination with Piperine and Piperine derivatives were investigated by validated HPLC method as per USFDA guidelines. It was seen that the two synthesized derivatives of Piperine significantly improved the bioavailability of Simvastatin in Wistar rats. The 5-(benzo) [1,3]dioxol-5-yl)-N-(pyridin-4-yl)penta-2,4-dienamide was better amongst the synthesized in increasing the bioavailability of Simvastatin in Wistar rat.     

Stability Study of Hard Gelatin Capsules Containing Retinoic Acid

Retinoic acid (RA) is employed in the therapeutic treatment of acute promyelocytic leukemia (APL). In this paper, the chemical stability and the most favorable storage conditions of RA in hard gelatin capsules containing α-lactose monohydrate, used in clinical experimentation, are reported. A secondary goal of this work was to show the usefulness of a robust regression technique, repeated median with replicates (RMWR) in a solid-state shelf life prediction by accelerated studies. The capsules were stored at room temperature and in the freezer. Their residual RA content was assayed for more than 3 years. RA chemical degradation was monitored by high-performance liquid chromatography (HPLC) and thin-layer chromatography (TLC) stability-indicating methods previously validated and able to detect various potential degradation products. Possible physical modifications were checked by dissolution tests and differential scanning calorimetry (DSC) of the content of the capsules. The shelf life was also predicted by an accelerated isothermal method to confirm room temperature results, and the activation energy estimated through this study was 12.5 ± 1.1 kcal/mol (95% confidence interval). In the conditions of climatic zone II, the shelf life for the capsules stored at room temperature in light-resistant containers was equal to 678 days, while the capsules stored in the freezer retained the initial content of drug after 1289 days. From the results gathered in this study, the usefulness of RMWR for shelf life prediction in the presence of outliers is evident.     

Aging bulk modulus obtained from enthalpy and volume relaxations of a-PMMA and its blends with PEO

Enthalpy and volume relaxation data measured on atactic poly(methyl methacrylate) and its blends with poly(ethylene oxide) are used to calculate an aging bulk modulus, K _a , tentatively defined as the derivative (∂ h∂ v) _T . The K _a values are mainly lower than the corresponding bulk modulus data determined directly with a piston-type PVT-device. On the whole, however, the K _a values can be considered as lying close to the moduli measured in the liquid state. This notion is supported by K _a data measured on amorphous selenium, which has a significantly lower compressibility in the liquid state than common amorphous polymers. The results are discussed in terms of thermodynamics of irreversible processes using a single internal variable, yet without arriving at suitable expression for the enthalpy/volume derivative.     

Stability of extemporaneous norfloxacin suspension

The stability of norfloxacin as extemporaneous suspensions compounded from two brands of film-coated tablets (formulas I and II) was studied. The vehicle consisted of tragacanth, saccharin sodium, sorbitol solution, glycerin, paraben concentrate, peppermint spirit BP, purified water, and syrup USP. The final concentration of norfloxacin in the suspensions was 20 mg/ml. Formulas I and II were chemically stable for 28 days when stored in amber glass bottles at ambient temperature; however, their physical characteristics were different.     

Stability of Extemporaneous Norfloxacin Suspension

The stability of norfloxacin as extemporaneous suspensions compounded from two brands of film-coated tablets (formulas I and II) was studied. The vehicle consisted of tragacanth, saccharin sodium, sorbitol solution, glycerin, paraben concentrate, peppermint spirit BP, purified water, and syrup USP. The final concentration of norfloxacin in the suspensions was 20 mg/ml. Formulas I and II were chemically stable for 28 days when stored in amber glass bottles at ambient temperature; however, their physical characteristics were different.     

车辆稳定性和倾翻测量系统的研发

为了严格按照国家标准对车辆稳定性能进行测试,本文研发出了一种车辆稳定性和倾翻测量系统。系统由硬件软件两大部分组成(共包含五个子系统),能够在不损坏测试设备的前提下进行有关车辆(上方机械、叉车及其它车辆)的稳定性测试和车辆的倾翻测试。系统具有原理清晰可靠、控制方式先进等特点,适用于相关车辆的稳定性和倾翻测试。     

Thermal Stability and Transformation-mediated Deformability of Cu-Zr-Al-Ni Bulk Metallic Glass Composite

The glass-forming ability and the thermal stabilityof Cu45Zr45Al5Ni5 metallic glass were systematically investigated by the differential scanning calorimetry.The activation energies for the glass transition and the onset crystallization and the crystallization peak were calculated to be 255.1,308.7 and 311.5 kJ/mol,respectively,while the corresponding liquid fragility was determined to be 23.4.By controlling the casting process,Cu45Zr45Al5Ni5 bulk metallic glass composite with the presence of ductile B2 CuZr phase was fabricated.The composite shows a pronounced plastic strain of 6.8 0.05% with obvious work hardening,which results from the formation of multiple shear bands and the deformation-induced martensitic transformation.     

Comparative analysis of temperature thermally induced instability between Si-In-Zn-O and Ga-In-Zn-O thin film transistors

Thermally induced instability of amorphous Si-In-Zn-O (SIZO) with 1 wt.% silicon (Si) concentration and Ga-In-Zn-O (GIZO) with gallium (Ga) of 30 wt.% thin film transistors (TFTs) has been investigated, by comparing the density of states extracted from multi-frequency method. It was observed that the density of state of SIZO-TFT was lower than that of GIZO-TFT, in spite of low processing temperature of SIZO-TFT and thermally induced instability of SIZO- and GIZO-TFT was strongly related with the total trap density. We report that Si of only 1 wt.% in SIZO can improve thermal stability of threshold voltage of In-Zn-O based TFTs more effectively than Ga of 30 wt.% in GIZO.     

Assessing Lipid Lowering and Plasma Cholesteryl Ester Transfer Protein Activity of Simvastatin Following Administration to Rabbits Fed a High Fat/Cholesterol Diet

ABSTRACT

Purpose: The purpose of this study was to assess the lipid lowering and plasma cholesteryl ester transfer protein (CETP) activity following administration of simvastatin to rabbits fed a high fat/cholesterol diet. Methods: Male New Zealand white rabbits were housed in individual cages and fed a standard diet for 7 days. After 7 days, animals were fed 10 g of a regular chow diet plus 100 g of the same diet supplemented with 0.5% (w/v) cholesterol and 14.0% (w/v) coconut oil for 28 days. Following 28 days on this diet, the animals were randomized based on plasma cholesterol and triglyceride levels, into a group of control animals and a group (n = 6) of animals fed 100 g of cholesterol/coconut diet plus 10 g regular chow diet containing simvastatin (3 mg/kg/day) for an additional 28 days. Blood samples were taken from the marginal ear vein prior to and 28 days after the initiation of drug treatment. Plasma was harvested and stored at 4°C prior to lipid analysis. Plasma total cholesterol and triglyceride levels were quantified using enzymatic kits. HDL (high-density lipoproteins) cholesterol levels were determined using the dextran sulfate-Mg²⁺ precipitation method. ApoB cholesterol levels were determined by subtracting total cholesterol from HDL cholesterol. Cholesteryl ester transfer protein (CETP) activity was determined by standard assay methods. Results: We observed that simvastatin significantly reduced total plasma cholesterol, triglyceride, and apoB cholesterol compared to non-treated controls. Simvastatin treatment did not alter serum CETP activity compared to non-treated controls. Conclusions: These findings suggest that decreasing plasma lipid levels by treatment with simvastatin is not due to changes in serum CETP activity in rabbits fed a high fat/cholesterol diet.     

Enthalpy relaxation studies of two structurally related amorphous drugs and their binary dispersions

Objective: The purpose of the current study was to evaluate the enthalpy relaxation behavior of valdecoxib (VLB) and etoricoxib (ETB) and their binary dispersions to derive relaxation constants and to understand their molecular mobilities. Methods: Solid dispersions of VLB and ETB were prepared with 1%, 2%, 5%, 10%, 15%, and 20% (w/w) concentrations of polyvinylpyrrolidone (PVP) in situ using differential scanning calorimetry (DSC). Enthalpy relaxation studies were carried out with isothermal storage periods of 1, 2, 4, 6, 16, and 24 hours at 40°C and 0% relative humidity (RH). Results: PVP increased the glass transition temperature (T_g) and decreased the enthalpy relaxation. Significant differences between two drugs were observed with respect to their relaxation behavior which may be due to differences in intermolecular interactions as predicted by Couchman–Karasz equation and molecular mobility. Kohlrausch–Williams–Watts equation was found to be inadequate in describing complex molecular relaxations in binary dispersions. The enthalpy relaxation behavior of VLB and ETB was found to be significantly different. PVP stabilized VLB significantly; however, its effect on ETB was negligible. The extent of enthalpy relaxation was found to correlate with hydrogen bonding tendency of the drug molecules. Conclusion: The outcome can help in rational designing of amorphous systems with optimal performance.     

Physicochemical Characterization of Rutaecarpine-Loaded Microemulsion System

To develop an o/w microemulsion system containing poorly water-soluble rutaecarpine, the solubility of rutaecarpine in water, ethanol, various oils, and surfactants were investigated. Among the surfactants and oils tested, Tween 20/PEG 400 and castor oil were chosen as the surfactant system and oil phase of the microemulsion, as rutaecarpine was most soluble in them, respectively. Pseudoternary phase diagrams were constructed to obtain the concentration range of oil, surfactant, and cosurfactant for microemulsion formation, and the stability test of rutaecarpine delivered by microemulsion formation was then evaluated. Pseudoternary phase diagrams show that the areas of microemulsion appeared at those with 0–20% Smix (PEG 400/Tween80 = 60/40), 64–81% water, and 10–20% oil. The rutaecarpine (300 µg/g)-loaded microemulsion composed of 10.8% PEG 400, 7.2% Tween 80, 20% caster oil, and 72% water was physically and chemically stable for at least 6 months. Thus, the microemulsion system composed of castor oil, PEG 400, Tween 80, and water could be a stable dosage form for rutaecarpine.