Preliminary Stability Studies Research Articles

Pharmaceutical development and optimization of azithromycin suppository for paediatric use

Pharmaceutical development and manufacturing process optimization work was undertaken in order to propose a potential paediatric rectal formulation of azithromycin as an alternative to existing oral or injectable formulations. The target product profile was to be easy-to-use, cheap and stable in tropical conditions, with bioavailability comparable to oral forms, rapidly achieving and maintaining bactericidal concentrations. PEG solid solution suppositories were characterized in vitro using visual, HPLC, DSC, FTIR and XRD analyses. In vitro drug release and in vivo bioavailability were assessed; a study in rabbits compared the bioavailability of the optimized solid solution suppository to rectal solution and intra-venous product (as reference) and to the previous, non-optimized formulation (suspended azithromycin suppository). The bioavailability of azithromycin administered as solid solution suppositories relative to intra-venous was 43%, which compared well to the target of 38% (oral product in humans). The results of 3-month preliminary stability and feasibility studies were consistent with industrial production scale-up. This product has potential both as a classical antibiotic and as a product for use in severely ill children in rural areas. Industrial partners for further development are being sought.

The Brief Introduction of High-Speed Trimaran Planing Hull and the Preliminary Study of the Longitudinal Stability

The character of lines and high-speed performance of trimaran planing hull is briefly introduced. By use of model experiments the law of longitudinal motion stability of the trimaran planing hull is studied. According to the combination of upper and lower speed limits at which the dolphin motion takes place at different displacements and the positions of gravity, these critical points from the experiments are linearly fitted by using MATLAB in order to obtain the limit curve. The veracity of the limit curve to evaluate the longitudinal stability is proved.

Stability and sensory assessment of emulsions containing propolis extract and/or tocopheryl acetate

The prevention of skin aging has been one of the main aims of cosmetic products. Propolis and tocopheryl acetate can be promising substances because of their antioxidant properties. In this study, propolis extract was obtained and associated with tocopheryl acetate in a cream formulation, which then underwent stability and sensory assessment. The formulation containing propolis extract and tocopheryl acetate proved to be stable in the preliminary stability study, demonstrating gradual darkening and slight pH decrease when subjected to 60ºC for 28 days, but showing stability on rheological study. In the sensory analysis, the formulation containing these two components was preferred by the product testers over the base cream and creams containing propolis extract or tocopheryl acetate alone. In conclusion, given the stability of the formulation and the preference of the product testers for this formulation, this association proved promising for use in cosmetic formulations.

Preparation and Characterization of Tablet Formulation based on Solid Dispersion of Glimepiride and Poly(ester amide) Hyperbranched Polymer

The feasibility of incorporating a solid dispersion containing poorly soluble antidiabetic drug glimepiride and poly(ester amide) hyperbranched polymer into a tablet using a direct-compression tabletting technique was investigated. Tablet cores were additionally coated with hydroxypropyl methylcellulose phthalate in order to protect the extremely hygroscopic solid dispersion from atmospheric moisture. Preliminary stability studies show that glimepiride, which is in amorphous form within solid dispersion, is chemically stable, even if tablets are exposed to elevated temperature and/or moisture. In-vitro dissolution studies show some impact of storage conditions on the tablet cores disintegration time and, consequently, drug release rate. Glimepiride solubility also deteriorates somewhat, most probably due to its partial recrystallization. Storage conditions much less affect the physical stability of coated tablets, which was ascribed to reduced tablet hygroscopicity due to the presence of protecting coating. The hyperbranched polymers are rather new and complex macromolecules. Therefore, we addressed also the biocompatibility of hyperbranched polymer, i.e., its impact on haemolysis of the red blood cells. The concentration required for the haemolytic effect on the red blood cells is around 100-times higher than its expected gastrointestinal luminal concentration, which makes the occurrence of hyperbranched polymer mediated cytotoxicity very unlikely.

Comparative Analysis ofSambucus nigraandSambucus australisFlowers: Development and Validation of an HPLC Method for Raw Material Quantification and Preliminary Stability Study

This work was designed to develop a simple, effective, and reliable LC system to identify a chemical marker and compare Sambucus nigra L. and Sambucus australis Cham. et Schltdl. flower extracts (American and European elder). Rutin was the main constituent of both species. The developed method showed a linear response in the range of 10 to 45 microg x mL(-1) for rutin and 1.75 to 3.25 microg x mL(-1) for samples of the Sambucus species. Precision was determined and the relative standard deviations were 1.75 % for HSN and 1.28 % for HSA for intraday precision and 1.28 % and 1.51 % for inter-day precision, respectively, while accuracy was 97.9 % for HSN and 99.41 % for HSA. Quantification and detection limits as well as robustness were determined, presenting adequate results. The LC method showed an adequate performance for the separation of flavonoid glycosides in S. nigra and S. australis extracts, since the presence of interference had been previously evaluated. The analysis of thirty different samples of S. NIGRA and S. australis of different origins did not show significant variability among them. An accelerated stability study revealed a significant decrease in the first 30 days reaching 57 % in 90 days for S. australis samples and a total decrease of 25 % in 90 days for S. nigra samples, considering rutin as the chemical marker. These results will contribute to quality control analysis routines of these raw materials in pharmaceutical production facilities.

γ Doradus variable stars in the Pleiades cluster: results from a photometric multiste campaign

The variability of the two γ Doradus star belong to Pleiades cluster, HD 22702 and HD 23585, have been confirmed by using new photometric measurements collected during a multisite campaign in 1998. Respect to previous observing runs, the frequency analysis shows new peaks close the 3 cd-1 for both stars. With the aim of performing a modal identification, the method based on amplitudes ratios and phase shifts with non-adiabatic time dependent convection (TDC) has been applied. The physical parameters obtained from the photometry put the star HD 23585 out the blue observational edge of the γ Dor region in the HR diagram. This behaviour together with the high value of vsini have not allowed us to perform an identification of the excited modes. Respect to the the star HD 22702, a preliminary study of stability provides results consistent with a l = 2 identification for the found oscillation frequencies except for f3, where a l = 1 mode is also probable. Also for this star, the TDC treatment has not been able to discrimante the found modes. Therefore, in addition to new vsini measurements, it is fundamental to carry out an exhaustive modelling by considering the pertinent corrections in the rotation.

Development of a Melting Tablet Containing Promethazine HCl Against Motion Sickness

The purpose of this study was to design a 'Traveller Friendly Drug Delivery System' for PM-HCl. Conventional promethazine (PM-HCl) tablets are bitter, need to be taken 1 h before symptoms and water is also needed. Taste-masked granules were produced with Eudragit E100 by extrusion, and analyzed with FTIR, DSC, and XRD. Tablets formulated from granules by direct compression using Ac-Di-Sol, Polyplasdone-XL, Primojel and ion-exchanger Tulsion339 and evaluated for mass uniformity, friability, tensile strength, drug content uniformity, water absorption ratio, in-vitro and in-vivo disintegration time and in-vitro dissolution studies. The observed drug-polymer interactions and reduced crystallinity may be reasons for increased dissolution rates. The formulated tablets were disintegrated within 15 s. Tablets (25 mg PM-HCl) with Ac-Di-Sol (4%) showed complete release within 1 min, while marketed conventional tablets (Phenergan; Rhone-Poulec) release 25% during the same period. A preliminary stability studies for the prepared tablets carried at 30 +/- 2 degrees C/60 +/- 5% RH, and 40 +/- 2 degrees C/75 +/- 5%RH for 3 months showed no significant changes in the tablets quality at 30 +/- 2 degrees C/60 +/- 5% RH. However, at 40 +/- 2 degrees C/75 +/- 5%RH marked increase in in-vitro disintegration time, tensile strength and decrease in friability and water absorption ratio was found. The present studies indicate the abilities of Eudragit E 100 for taste masking and improving the dissolution profile of PM-HCl after complexation. In addition, by employing cost effective direct compression method, fast-dissolving tablets of 400 mg total weight with an acceptable quality could be prepared.

Tailoring Electrolyte Composition for LiBOB

Realizing that organic carbonates might not be the optimum solvents for lithium bis(oxalato)borate (LiBOB), efforts were made to tailor a “dedicated” electrolyte composition for this new salt. It was discovered that lactone-based cosolvents can effectively dissolve LiBOB up to high concentrations, and the electrolytes thus formulated generate high ionic conductivity as well as low interfacial resistance on graphitic electrode. However, lactones tend to increase the irreversible capacity associated with the reduction process of bis(oxalato)borate (BOB) anion on carbonaceous anode surface, while performances of the lithium-ion cells at elevated temperatures deteriorate with the lactone content. Thus, compromises have to be made by using linear carbonates to suppress the irreversible capacity in the formation cycles and ethylene carbonate to improve the thermal stability of the interfacial films formed. A preliminary study of LiBOB anodic stability on various cathode surfaces seems to indicate that the oxidative decomposition of BOB anion is catalyzed by Co-rich surfaces.

Very low frequency EEG oscillations and the resting brain in young adults: a preliminary study of localisation, stability and association with symptoms of inattention

Spontaneous very low frequency oscillations (VLFO: <0.2 Hz) in functional magnetic-resonance imaging are proposed to identify a default-mode network of resting brain activity. Activity in this network has been related to lapses of attention during goal-directed tasks and may provide a basis for ADHD. This study assessed the relation between scalp-recorded EEG VLFO at rest and ADHD. 13 young adults with high- and 11 with low self-ratings of ADHD participated. Direct current EEG was recorded during a five minute rest session and was retested after approximately 1 week. A consistent and temporally stable pattern of VLFOs was observed across specific scalp regions in low-ADHD participants. High-ADHD participants had less VLFO power across these locations, especially where inattention self-ratings were high. Inattention was not related to VLFO power in other locations. Initial evidence is provided for a pattern of VLFOs at rest which is associated with inattention symptoms.

Preparation and evaluation of candidate certified reference materials (CRMs) for nutrients in seawater

Certified reference materials (CRMs) are an essential part of the quality assurance (QA) necessary for the reliable analytical measurement of nutrients in seawater. The CRMs currently available for these analyses are not matrix matched to marine samples. QUASIMEME routinely produces test materials for the nutrients in seawater and nutrients in estuarine water and low-salinity open water Laboratory Performance Studies (LPS) that are both homogeneous and stable. QUASIMEME, in conjunction with Eurofins Scientific, Denmark have produced two reference materials (RMs). The homogeneity testing and preliminary stability studies were carried out by QUASIMEME, and the results are presented in this article. Participants of the QUASIMEME LPS who demonstrated satisfactory long-term performance for the analysis of nutrients in seawater and nutrients in estuarine water and low-salinity open water were invited to take part in the certification exercise. Twenty laboratories returned data, a summary of which is also presented. The certification and long-term stability testing and additional data analysis were carried out by Eurofins Scientific, Denmark, and are outwith the scope of this article and not reported here. Eurofins Scientific, Denmark have marketed these RMs as part of their range of VKI Reference Materials (further information is available from eurofins@eurofins.dk).

Microbiological Assay for the Determination of Telithromycin in Tablets

This study describes the development and validation of a microbiological assay, applying the cylinder-plate method, for the determination of the antibiotic telithromycin. The microbiological method consisted of a cylinder-plate agar diffusion assay using Micrococcus luteus ATCC 9341 as the test microorganism. The response graphs for standard and sample solutions were linear (r = 0.9987), and no parallelism deviations were detected in the tested concentrations (0.25, 0.5, and 1.0 microg/mL). The interday precision was 2.67%. Recovery values were between 96.75 and 100.91%. A preliminary stability study of telithromycin showed that the microbiological assay is specific for the determination of telithromycin in the presence of its degradation products. The proposed method allows the quantitation of telithromycin in pharmaceutical dosage form and can be used for drug analysis in routine quality control.

Quasilocal formalism and black-ring thermodynamics

The thermodynamical properties of a dipole black ring are derived using the quasilocal formalism. We find that the dipole charge appears in the first law in the same manner as a global charge. Using the Gibbs-Duhem relation, we also provide a non-trivial check of the entropy/area relationship for the dipole ring. A preliminary study of the thermodynamic stability indicates that the neutral ring is unstable to angular fluctuations.

A preliminary study of the metabolic stability of a series of benzoxazinone derivatives as potent neuropeptide Y5 antagonists

The metabolic stability of benzoxazinone derivatives, a potent series of NPY Y5 antagonists, has been investigated. This study resulted in the identification of the structural moieties prone to metabolic transformations and which strongly influenced the in vitro half-life. This provides opportunities to optimize the structure of this new class of NPY Y5 antagonists.

Microbiological assay for the determination of meropenem in pharmaceutical dosage form

Meropenem is a highly active carbapenem antibiotic used in the treatment of a wide range of serious infections. The present work reports a microbiological assay, applying the cylinder-plate method, for the determination of meropenem in powder for injection. The validation method yielded good results and included linearity, precision, accuracy and specificity. The assay is based on the inhibitory effect of meropenem upon the strain of Micrococcus luteus ATCC 9341 used as the test microorganism. The results of assay were treated statistically by analysis of variance (ANOVA) and were found to be linear ( r = 0.9999) in the range of 1.5–6.0 μg ml −1, precise (intra-assay: R.S.D. = 0.29; inter-assay: R.S.D. = 0.94) and accurate. A preliminary stability study of meropenem was performed to show that the microbiological assay is specific for the determination of meropenem in the presence of its degradation products. The degraded samples were also analysed by the HPLC method. The proposed method allows the quantitation of meropenem in pharmaceutical dosage form and can be used for the drug analysis in routine quality control.

Cationic Polymerization of p-Methoxystyrene in Water with Dodecylbenzenesulfonic Acid and Ytterbium Triflate: Evidence for an Inverse Emulsion Process

The cationic polymerization of p-methoxystyrene in water using dodecylbenzenesulfonic acid as a surfactant and ytterbium triflate as a catalyst was studied in terms of kinetics and physicochemistry. Preliminary stability studies showed that stable inverse (water in monomer) emulsions were obtained using excess catalyst and cocatalyst. Rates of polymerization and molar masses were respectively found slower and larger than for direct emulsion processes, in accordance with previous results published by Sawamoto on similar systems. The presence of the catalyst did not affect the mechanism scheme of ionic polymerization in aqueous dispersion; i.e., the polymerization is interfacial, and physicochemical issues govern molar masses.

On the synthesis of Zr-based bulk amorphous alloys from glass-forming compounds and elemental powders

The possibility of producing Zr-based bulk amorphous alloys (Zr65Cu17.5Ni10Al7.5 and Zr57Ti5Cu20Ni8Al10) by mechanical alloying (MA) from either a mixture of elemental powders (EP), or a mixture of glass-forming compounds (GFC), has been investigated. A preliminary study of the crystal structure stability of the GFC-ingredients during mechanical milling was performed. Amorphization was found to be significantly enhanced during MA by using a GFC mixture. A considerable difference in the phase transformations observed on heating the amorphous phase (AP) was noted for alloys obtained from GFC, as compared with those produced by melt quenching (MQ) or milling of a mixture of elemental powders. It is shown that the amorphous phase obtained by MA from GFC has a wider undercooled liquid region between the glass transition temperature Tg and the crystallization temperature Tx than the amorphous phase produced by the conventional MQ technique.

Intestinal permeability of chlorpyrifos using the single-pass intestinal perfusion method in the rat

The intestinal transport of chlorpyrifos (CPF), an organothiophosphate pesticide, was investigated using the single-pass intestinal perfusion (SPIP) technique in male, Sprague–Dawley rats. SPIP was performed in each isolated region of the small intestine (i.e. duodenum, jejunum and ileum) with three concentrations of CPF (0.1, 2.0 and 10 μM) at a flow rate of 0.25 ml/min. Preliminary binding and stability studies were conducted to ensure that the loss of CPF in the SPIP study can be attributed to intestinal absorption. The effective permeability ( P eff) of CPF was determined for each segment and concentration. CPF exhibits a high intestinal permeability over the length of the small intestine indicative of compounds that are well absorbed. Decreases in permeability values at the highest CPF concentration studied in the duodenum and ileum suggest a saturable transport process. Based on these results, passive, transcellular diffusion dominates the intestinal transport mechanism of CPF, with a saturable transport process evident in the duodenum and ileum. The P eff of CPF is in the range of drugs with high intestinal permeability and high fraction of dose absorbed indicating that CPF readily crosses the intestine. The dependence of CPF's P eff on concentration in the duodenum and ileum suggests that CPF is transported by a combination of mechanisms across the intestine. Using established relationships, the human fraction dose absorbed for CPF was estimated to be >99%. The permeability values obtained from this study may be useful in models of exposure assessment.

High-performance rare earth/transition metal magnetostrictive materials

In a previous study, hydroxypropyl cellulose (HPC)-based capsular shells prepared by injection molding and intended for pulsatile release were successfully coated with 10 mg/cm2 Eudragit® L film. The suitability of HPC capsules for the development of a colon delivery platform based on a time dependent approach was demonstrated. In the present work, data logging devices (PyroButton®) were used to monitor the microenvironmental conditions, i.e. temperature (T) and relative humidity (RH), during coating processes performed under different spray rates (1.2, 2.5 and 5.5 g/min). As HPC-based capsules present special features, a preliminary study was conducted on commercially available gelatin capsules for comparison purposes. By means of PyroButton data-loggers it was possible to acquire information about the impact of the effective T and RH conditions experienced by HPC substrates during the process on the technological properties and release performance of the coated systems. The use of increasing spray rates seemed to promote a tendency of the HPC shells to slightly swell at the beginning of the spraying process; moreover, capsules coated under spray rates of 1.2 and 2.5 g/min showed the desired release performance, i.e. ability to withstand the acidic media followed by the pulsatile release expected for uncoated capsules. Preliminary stability studies seemed to show that coating conditions might also influence the release performance of the system upon storage.

Optical NO 2 sensing based on sol–gel entrapped azobenzene dyes

A novel thin film based on an azobenzene chromophore incorporated into a sol–gel network is demonstrated to be sensitive to NO 2 gas and shows comparable sensing performance to a Langmuir–Blodgett (LB) film of the same chromophore attached to a polysiloxane backbone. Sensing was carried out by UV–Visible absorption spectroscopy monitoring increase in the n– π* transition at 475 nm with simultaneous decrease in the π– π* transitions at 240 nm and 360 nm on exposure to 100 ppm NO 2 gas. Preliminary stability studies show only a limited loss of response (<5%) on repeated gas exposure. Increasing the temperature from 293 K to 313 K caused a decrease in the response of the sol–gel system similar to that observed in the Langmuir–Blodgett film of the polysiloxane derivative, suggesting this to be a fundamental temperature property of the chromophore–gas interaction. The sol–gel immobilization approach provides a convenient route to sensors based on this principle.

Magnetic Properties of Hitperm (Fe,Co)88Zr7B4Cu1 Nanocrystalline Magnets (Invited)

ABSTRACTAlloys consisting of Fe-Co-M-B-Cu (with M = Zr, Hf, Nb), called HITPERM alloys, have been developed. Synchrotron X-radiation studies have been used to show that the ferromagnetic phase in an equiatomic FeCo-based alloy is the α'-FeCo phase. Since both the α'-FeCo phase and the FeCo-based amorphous phase of the nanocrystalline alloy have high Curie temperatures, a high magnetization persists up to the α -&gt; γ structural phase transformation temperature of 980°C. Room temperature AC permeability measurements have shown that the alloys maintain a high permeability of ∼2000 up to a frequency of 20 kHz. The room temperature core loss has also been shown to be competitive with commercial high temperature magnetic alloys with a value of 1 W/g at Bs = 10 kG andf= 10 kHz. Analysis of extended X-ray absorption fine structure (EXAFS) data is consistent with a two-phase mixture of nanocrystalline body centered cubic derivative FeCo structure and an amorphous Zr-rich phase. A differential scanning calorimetry study of the primary crystallization reaction shows an activation energy of 323.3 kJ/mol. As a preliminary study of phase and grain stability, broadening of X-ray diffraction peaks indicates little grain growth after annealing at 600 °C for 3072 hours.