Reconstitution Of Powders Research Articles

FDA approves fibrinogen concentrate product

The plasma-derived fibrinogen product Riastap, from CSL Behring, was approved by FDA on January 16 for the treatment of bleeding in patients with congenital fibrinogen deficiency. An estimated 1 or 2 individuals per 1 million have the deficiency, according to the National Hemophilia Foundation. For those patients, CSL Behring said, Riastap is the only FDA-licensed treatment for episodes of acute bleeding, which can be life threatening. The labeling for the new product states that the dosage, duration of treatment, and frequency of administration of fibrinogen concentrate depends on the clinical condition of the patient, laboratory test values, and the extent of the bleeding. Treatment should target a plasma fibrinogen concentration of 100 mg/dL until hemostasis is achieved. Allergic reactions and generalized reactions, such as chills, fever, nausea, and vomiting, were the adverse reactions most commonly reported during clinical studies of the product and postmarketing surveillance in other countries. CSL Behring will distribute Riastap as single-use vials containing 900–1300 mg of lyophilized fibrinogen concentrate powder for reconstitution with 50 mL of sterile water for injection. Packages of Riastap do not contain the diluent. Doses should be administered at room temperature by slow i.v. injection at a rate not exceeding 5 mL/min.

Reinforcing and toughening alumina/titania ceramic composites with nano-dopants from nanostructured composite powders

Nanostructured alumina/titania composite powders were prepared using nanosized alumina and titania doped with nanosized zirconia and ceria through ball-milling, spray drying and heat treating. The nanostructured reconstituted powders were then cool isostatic pressed and pressureless sintered into bulk ceramic composites. The phase constitution and microstructures of as-prepared ceramic composites were characterized by using X-ray diffractometer and scanning electron microscope. The mechanical properties of the ceramic composites were evaluated by Vickers hardness test, flexural strength test and fracture toughness test. The effects of nano-dopants and sintering temperatures on the microstructures and mechanical properties of the composites were investigated. It was found that nano-dopants had the effects of lowering sintering temperature, accelerating densification, reinforcing and toughening the composites. The maximum flexural strength, fracture toughness and Vickers hardness of the composites with nano-dopants were 51, 20 and 56% higher than that of the composites without nano-dopants. The reinforcing and toughening mechanisms are discussed in detail.

Powder for reconstitution of the anti-HIV-1 drug TMC278 – Formulation development, stability and animal studies

Powders for reconstitution of the next-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) TMC278 with low water solubility were developed by using a spray-dry technology. Their flexible dosing ability makes them suitable for patients looking for a different approach for antiretroviral (ARV) therapy. The selection of formulation excipients was based on their potential to create and maintain supersaturation solubility of TMC278 in 0.01 M HCl. Suitable water-soluble carriers for TMC278 were selected by a supersaturation screening to formulate powders for reconstitution by spray-drying. The selected powders for reconstitution were compared to clinical tablets of TMC278.HCl, in vitro using dissolution and stability testing, and in vivo through administration to beagle dogs, fed immediately after dosing. The spray-dried powders for reconstitution made up of TMC278/PVP-VA 64 1:9 (w/w) and TMC278/PVP-VA 64/Cremophor EL 1:8.5:0.5 (w/w/w) showed ease of suspendability, nearly complete dissolution of the drug and acceptable stability after one month storage at 25 and 40 °C. In dogs, TMC278 was more slowly absorbed from tablets than from the suspended powders for reconstitution. Compared to the tablet, the relative bioavailability obtained with the powders ranged between 69% and 89% for TMC278/PVP-VA 64 1:9 (w/w) and between 85% and 157% for TMC278/PVP-VA 64/Cremophor EL 1:8.5:0.5 (w/w/w). The absence of differences in vivo and in vitro between the powders made an eventual choice very difficult, yet their advantageous in vivo behaviour and flexible dosing possibility may provide a starting point for paediatric formulations.

Preparation and sintering behaviour of nanostructured alumina/titania composite powders modified with nano-dopants

Nanostructured alumina/titania composite powders were prepared by doping with small amounts of nanosized zirconia and ceria. The nanosized raw materials powders were reconstituted into nanostructured particles by ball milling, spray drying and heat treating. Then, the nanostructured reconstituted powders were cool-isostatic pressed and pressureless-sintered into bulk ceramics. The phase composition and microstructures of reconstituted powders and as-prepared ceramic composites were characterized by using X-ray diffractometer (XRD), scanning electron microscope (SEM) and energy-dispersive spectrometer (EDS). The sintering behaviour of the nanostructured ceramic composite powders and the effects of nano-dopants and sintering temperatures on the microstructures of the ceramic composites were investigated and discussed. It was found that nano-dopants could lower the sintering temperature and accelerate densification of ceramic composites.

Quality of Chlorine-Based Antiseptics and Disinfectants Circulating in Dar es Salaam, Tanzania

Background: Chlorine-based antiseptics and disinfectants have a stability problem especially when formulated as aqueous solutions. They tend to decompose slowly liberating chlorine on storage. Despite this instability, these products are commonly manufactured and labeled with a long shelf-life. Thus the labeled content of available chlorine is doubtful and this could pose a danger to public health by not providing adequate disinfection. Broad Objective: This study aimed at assessing the quality of chlorine-based antiseptics and disinfectants circulating in Dar es Salaam, Tanzania. Study setting: The study was carried out in the city of Dar es Salaam Methods and materials: Nineteen (19) samples representing various product batches circulating in Dar es Salaam were collected randomly from pharmacies, shops and from a tertiary-level public hospital. Analysis of the samples was immediately done in which the content of available chlorine was determined using a titrimetric method (Iodometric titration) according to the British Pharmacopoea (BP) specifications. Measures of outcome: Results for contents of available chlorine was compared to the limits of assay specified in the BP and thus the percent compliance was calculated. Samples with contents below that specified in the BP were deemed to have failed the quality tests. For those products for which no official specifications are available (eg. Waterguard®), the BP limits for assay (± 10% of label claim) was applied to assess compliance. Results: Out of the 19 sample batches analyzed 12 (63%) did not comply with the specifications for available chlorine (BP Limits of Assay or within 90-110% manufacturer's label claim). This was especially serious with preparations containing calcium hypochlorite with boric acid (Eusol) which had a mean content of only 12% of the recommended strength. Conclusion and recommendations: The results from this study have shown clearly that chlorine-based antiseptics/disinfectant products should not be manufactured on a large scale by pre-dilution. Rather, they should be supplied as concentrates or powders for reconstitution at the time of use to ensure quality, efficacy and safety to public health. Tanzania Medical Journal Vol. 22 (1) 2007: pp. 17-19

Design of a novel recombination system

A novel recombination system was designed to control the rheological behaviour during reconstitution of milk powder by separating the mixing, pumping and heating processes. The application of high shear rate of 40,000 s −1 by recirculation through a capillary system suppressed the age thickening of the reconstituted concentrated milk solutions during recombination and allowed a more systematic study of this time dependent rheological system.

Dry Adsorbed Emulsion of Simvastatin: Optimization and In Vivo Advantage

In the present study, Simvastatin was incorporated in emulsion of soybean oil and propylene glycol monocaprylate as oily phase and Tween 80 and Cremophor EL as surfactants and also their mixtures. Dry adsorbed emulsions were prepared by using colloidal silicon dioxide in varying proportions to adsorb the liquid emulsion. Liquid emulsions were characterized for viscosity and mean globule size, and the dry adsorbed emulsions were evaluated for powder characteristics and reconstitution properties, dissolution profile, and for in vivo efficacy in rats. DSC and X-ray diffraction studies indicated complete amorphization and/or solubilization of Simvastatin in the dry adsorbed emulsion. It was supported by SEM studies, which did not show evidence of precipitation of the drug on the surface of the carrier. Dissolution studies revealed remarkable increase in dissolution of the drug compared to plain drug. One of the optimized formulations provided 10-fold enhancement in the dissolution compared to drug powder. After 24 hr of induction of hyperlipidemia in rats using poloxamer F127, administration of dry adsorbed emulsions effected significant reduction in the total cholesterol with levels of 439 mg/dL compared to 585 mg/dL of drug treated group (p < 0.01). Significant increase in the high-density lipoprotein levels were also observed after 4 days of treatment compare to positive control (p < 0.01).

CHARACTERIZATION OF RECONSTITUTED MILK POWDER BY ULTRASOUND SPECTROSCOPY

ABSTRACT When instant milk powder (IMP) is reconstituted with water, the product should resemble fresh milk. However, undissolved particles were found at the surface and in the bulk of the product. A visual reconstitution test (RT) is made on IMP to determine the reconstituted quality of the product. This test is directly linked to the presence of the undissolved particles. The particles found at the surface are formed by clustered liquid‐fat aggregates, which rise to the top of the milk and may give an impression of spoiled milk. The particles found in the bulk are small particles in the solution mostly composed of a protein gel. Because the repeatability and precision of the RT are very poor, a quantitative analytical technique is desirable. In this study we investigated five different quality milk powders by an ultrasound spectroscopy technique. The ultrasonic velocity and attenuation parameters were measured with a frequency scanning pulse echo reflectometer. We found that the ultrasonic velocity cannot be correlated to RT because the predominant phenomenon that affects the ultrasonic velocity is the physical state of the different components of the milk matrix (liquid fat, crystalline fat and lactose crystals), and this physical state is not a significant factor in powder quality. However, the ultrasonic attenuation coefficient is well correlated with RT. This is because, between two different quality powders, the most important factor that causes variation in the attenuation is scattering, correlated to particle size and to volume fraction rather than by the composition or physical state of the matrix and the same particle size factor, and volume fraction factor characterizes the powder reconstitution's quality.

Heat Processing in Infant Formulas Induces Changes in Copper Tissue Levels in Suckling and Weanling Rats

Aim: To assess the effects of dehydration, conventional in-bottle sterilization, and ultrahigh-temperature (UHT) sterilization, involved in the production of infant formulas, on the copper bioavailability in rats at two stages. Methods: Two-week-old suckling rats were fed a reconstituted powder (P1) and an in-bottle-sterilized liquid infant formula (SC1) in a drinking bottle for 7 days. Weanling rats were fed P1, SC1, another powder (P2), and a liquid UHT formula (UHT2) complemented with a standard rat diet. Intake, body weight, and percentage copper absorption were calculated, and whole-body, serum, liver, skin, and erythrocyte copper concentrations were determined. Results: Food intake, body weight, and copper intake were reduced in suckling rats consuming SC1, but the percentage copper absorption increased, and whole-body and tissue copper concentrations were unaffected, except for the erythrocyte copper concentration which was significantly higher as compared with pups fed P1. In weanling rats, the only difference observed was the significantly higher liver copper concentration in animals fed the diet containing P1 as compared with the diets containing SC1 and UHT2. Conclusions: Consuming the SC1 formula induced high erythrocyte copper levels in suckling rats, whereas the equivalent dehydrated formula (P1) induced elevated liver copper concentrations in weanling rats. This is associated with the different Maillard reaction products resulting from the processing of each infant formula and with the developmental stage of the animals.

Direct Determination of Free Methionine in Soy-Based Infant Formula

A method was developed for the direct determination of free methionine in soy-based infant formula, with analyte separation and quantitation by reversed-phase liquid chromatography (LC), and UV absorbance at 214 nm, respectively. Sample preparation required only dilution with mobile phase and syringe filtration. Using a 0.02M KH2PO4 mobile phase (pH adjusted to 2.9 with 85% o-phosphoric acid) and 0.7 mL/min flow rate, methionine eluted at approximately 8 min, and total run time was 14 min after column regeneration with acetonitrile-water. System linearity was demonstrated as peak area versus analyte concentration, ranging from 80 to 120% of the formula specification for free methionine (r > 0.999, and all residuals < 0.45%). Intermediate precision relative standard deviation values were < 1.5% for ready-to-feed and reconstituted powder samples, and recoveries ranged from 98.0 to 103.5% for inter-method comparison with an amino acid analyzer method. The limit of quantitation was 3 mg methionine/L in the "as fed" infant formula. Despite the relatively weak UV absorptivity of methionine, the 214 nm signal was sufficiently intense in the 30-65 mg/L (201-436 microM) range to afford quantitation by peak area proportionation versus a 2-point external standard calibration. This direct UV detection after reversed-phase LC separation provides a simple and accurate method for determining free methionine without derivatization.

Surface composition of spray-dried milk protein-stabilised emulsions in relation to pre-heat treatment of proteins

Several important technical properties of spray-dried food powders depend on particle–liquid interactions (e.g. wettability, dispersability) and particle–particle interactions (e.g. flowability). It can be assumed that the chemical composition of the surface layer of the particles to a large extent determine these properties. The present study has been aimed to investigate the relation between the surface composition of spray-dried milk protein-stabilised emulsions and pre-heat treatment of the proteins. Solutions of WPC were heat-treated at low (60–90°C) and high (140°C) temperature and the degree of denaturation was determined, prior to the preparation of emulsions with rapeseed oil. The surface composition of the dry powders were established by using ESCA (electron spectroscopy of chemical analysis). The emulsions were characterised by droplet size distribution before spray drying and after dissolution of the powders. Also free fat extractions and estimations of wettability (dissolution rates) were performed. The powder surface coverage of protein decreased with increasing degree of protein denaturation before the emulsification, whereas the emulsion droplet size increased both before spray drying and after reconstitution of powders. The free fat extraction as well as the dissolution rate, whereof the latter decreased with increasing surface fat coverage, correlated well with the fat coverage of the powder surface.

Milk fat microencapsulation using whey proteins

Abstract The effects of homogenisation conditions (pressure and number of passes) and emulsion composition (fat, whey protein, lactose, salts and water) on the properties of emulsions and microencapsulated milk fat powders were measured. The emulsions were assessed by fat globule diameter and size stability over time. The properties of the powders measured were particle diameter, reconstituted emulsion fat globule diameter, free fat, surface fat and fat oxidation. As expected, increasing homogenisation pressure reduced the fat globule diameter and increasing the number of homogenisation passes reduced the diameter of the largest globules. Increasing fat and salts reduced fat globule diameter stability after 2 homogenisation passes but the reduction in stability was less after 4 passes. Increasing the lactose : whey protein concentrate ratio reduced free fat and fat globule aggregation after powder reconstitution, but not the surface fat. The higher level of fat increased the surface fat on powder particles and the level of oxidation during storage.

Microstructure of whole milk powder and of insolubles detected by powder functional testing

AbstractThe functional properties of whole milk powder (performance during reconstitution in water and coffee) are routinely measured to determine powder quality. An examination of the microstructure of milk powder and of the insoluble material collected after applying a series of functional tests provided insight into why the insoluble material formed during reconstitution.The microstructures (transmission electron microscopy and confocal microscopy) of four commercial whole milk powder samples and of the insoluble material produced during functional testing were assessed. The microstructure of the whole milk powder could be related to features observed in the microstructure of some of the insolubles collected after powder functional testing. It is likely that heating conditions throughout the powder manufacturing process resulted in the denaturation of β‐lactoglobulin and its interaction with other proteins and fat globule membrane components, thus influencing the solubility of the milk powder. The application of shear during processing resulted in the greatest change to powder solubility in this study. Increasing homogenisation pressure during processing resulted in fat globule size reduction, adsorption of casein micelles to the fat globule membrane, and the formation of clusters of fat globules caused by the sharing of adsorbed casein micelles. The presence of large numbers of these clusters in the milk powder increased the formation of insoluble material during powder reconstitution in water and coffee.

Foam-mat drying of starfruit ( Averrhoa carambola L.) purée. Stability and air drying characteristics

Foams were prepared from starfruit ( Averrhoa carambola L.) purée by adding various concentrations of methocel. Overrun and density of the foams from various concentrations of methocel were compared. Relative stability of the foam was determined by comparing amounts of juice separated from foam at 70°C. Drying rates at two drying temperatures (70 and 90°C) were also compared. Quality of the dry and reconstituted powder was evaluated with simple sensory evaluation and Hunterlab instrument. Overrun and stability of foams increased with increasing methocel concentration until maximum value was obtained at a methocel concentration of 0.4% w/w. Falling rate was observed for foam dried at both temperatures. Drying time could be shortened by as much as 30 min when drying temperature was increased from 70 to 90°C. However, obvious colour and flavour changes were observed in the product dried at 90°C. This study has indicated that, under the experimental conditions employed, reasonably good powder characteristics can be obtained.

Dry powder inhalation as a potential delivery method for vaccines

Measles vaccine is administered to millions of children annually via a percutaneous injection. There are, however, compelling reasons to search for alternative routes of administration, especially in mass vaccination campaigns. Two key factors are (1) decreased stability of the vaccine upon reconstitution and, (2) the potential risks of contamination associated with needles. Dura has developed a unique inhaler that can deliver a powder dose via the pulmonary route for local or systemic action. The breath-actuated Spiros® inhaler uses electromechanical energy to aerosolize and deliver a consistent dose over a wide range of inspiratory flow rates. To achieve alveolar (deep lung) deposition for subsequent systemic absorption, dry-powder vaccine is size reduced to a mass median diameter between 1 and 5 μm. Small vaccine particles are blended with an inert carrier to improve dispersion. Measles vaccine formulated as a powder blend may be more thermostable than existing reconstituted formulations. The Spiros® technology is available in three powder storage platforms. Two of these formats are designed specifically for moisture and/or light sensitive compounds and may be particularly suitable for delivery of measles vaccines in mass campaigns because their design (1) eliminates the need for powder reconstitution, and (2) reduces the risk of contamination.

Growth and enterotoxin production by diarrhoeagenic Bacillus cereus in dietary supplements prepared for hospitalized HIV patients

This study was initiated because of an increase in diarrhoeal episodes in a ward caring for patients infected with the human immunodeficiency virus (HIV). An examination of hospital-prepared dietary supplements (build-up food) found Bacillus cereus to be a potential problem. Due in part to inadequate refrigeration conditions (13 ± 4 °C), the microbial flora in commercially pasteurized semi-skimmed milk (PSSM) reached potentially hazardous levels (>10 6 cfu/mL). While refrigerated PSSM did not support enterotoxin production, reconstitution of build-up powder in PSSM followed by storage in the HIV ward (4 h at 28 ± 3 °C) resulted in growth of B. cereus (>10 7 cfu/mL) and synthesis of diarrhoeal enterotoxin. While insufficient epidemiological data was available to establish conclusively a causal relationship between patients' symptoms and source, the study highlights a potential B. cereus problem with hospital-prepared dietary supplements and recommendations are proposed to prevent this re-occurrence.

Recombinant Interferon-??-1a*

This review focuses on Rebif, one of 2 available formulations of recombinant interferon-beta-1a, a molecule with the same molecular weight and primary structure as native interferon-beta. The product under review is intended for subcutaneous injection and contains 22 or 44microg of recombinant interferon-beta-1a. This molecule has the same antiviral, antiproliferative and immunomodulatory profile as native interferon-beta. Regulation of excessive immune responses in the inflamed lesions of patients with multiple sclerosis is thought to be important to its mode of action. In vivo studies indicate that the biological response to interferon-beta-1a is sustained with 3-times-weekly, in preference to once-weekly, administration. Subcutaneous interferon-beta-1a 22 and 44microg 3 times weekly for 2 years slowed sustained progression of disability (by 6.6 and 9.4 months; first quartile), decreased the mean number (by 27 and 33%) and severity of relapses, decreased the number of hospital visits and steroid courses, and decreased the acute activity [measured as the number of new or enlarging lesions seen with magnetic resonance imaging (MRI)] and burden (measured as the cumulative area or calculated volume of the lesions) of disease in patients with relapsing-remitting multiple sclerosis. All changes (except hospital visits: significant results were obtained with the higher dose only) were significant versus placebo with both doses. A recent study of once weekly interferon-beta-1a 22 or 44microg has confirmed the dose-dependency of the clinical and MRI effects. Patients with more severe disease appear to require the higher dosage regimen. Further studies of long term (>2 years) clinical efficacy, tolerability, and pharmacoeconomic aspects are required. Although injection site disorders and alterations in liver enzymes and lymphopenia are common, they rarely lead to withdrawal from treatment. As with other interferons, an influenza-like syndrome is often seen in patients receiving interferon-beta-1a. The sustained (over 2 years) presence of neutralising antibodies has been noted in 6 to 7% of patients; 16 to 18% of patients developed neutralising antibodies at some time during 2 years of treatment. This formulation is available as powder for reconstitution, or in liquid-prefilled syringes or an autoinjector device. Subcutaneous interferon-beta-1a 22 to 44microg 3 times weekly dose-dependently decreases the number and severity of relapses in patients with relapsing-remitting multiple sclerosis, slows the progression of disability, and decreases lesion activity and burden of disease. This formulation offers ease of dosage adjustment and convenience of administration, and is a valuable well-tolerated and effective addition to the choice of treatments for relapsing-remitting multiple sclerosis.

Evaluation of test conditions during the measurement of coffee stability of instant whole milk powder

Coffee provides a harsh environment for the reconstitution of milk powder with undissolved powder being manifested as undesirable ‘floaters' or ‘sinkers’. A coffee test method was adapted to explore the behaviour of a range of industrial samples of coffee stable and coffee unstable instant whole milk powders, under varying pH, temperature and water hardness. The development and application of a simulation test suggests evidence of some stabilizing contribution by the coffee itself. High surface fat coverage, as determined by electron spectroscopy for chemical analysis, and high ionic calcium levels were associated with instances of poor coffee stability. The effects of the physicochemical characteristics of the powders on coffee stability appear to predominate when various measures were implemented, such as prior reconstitution of the powder before addition to coffee, increased agitation and use of surface active agents, which succeeded in reducing coffee sediment.

Evaluation of Commercially Available Milk Powders for Calibration of Mid-Infrared Analyzers

Abstract The performance of commercially available shelf-stable milk powders that upon reconstitution can be used as calibration samples for mid-infrared (IR) analyzers was evaluated. Twelve reconstituted powders and 7 raw milk samples were sent to each of 7 laboratories. Each laboratory analyzed the reconstituted powders and milk samples by IR and obtained both corrected and uncorrected data. The corrected data reflected the current calibrations (based on calibration with fresh, raw milk) of each instrument. The uncorrected data from the reconstituted powders were used to derive separate calibration equations for each instrument. Two of the 12 reconstituted powers were discarded from the analysis because of poor quality. The abilities of the powder-based and current calibrations to predict accurately the total protein and fat contents of the 7 raw milk samples were compared. For the current and powder-based calibrations, respectively, the mean differences from chemical analysis for total protein were −0.006 and 0.031%, and the standard deviations of the differences (SDD) were 0.029 and 0.029%. For fat, the mean difference for the current calibration was −0.001%, and the SDD was 0.034%. For the powder-based fat calibration, the mean differences were 0.034% (fat A only), −0.047% (fat B only), and −0.061% (fat A and fat B), and SDDs were 0.046% (fat A only), 0.036% (fat B only), and 0.056% (fat A and fat B). The reconstituted powders did not provide as accurate an IR fat calibration for testing raw milk samples as can be obtained with raw milk calibration samples. This is attributed primarily to differences in the characteristics of the fat in the reconstituted powders and in raw milk. For protein, analytical precisions for both types of calibrations were comparable, and the positive bias for the powder-based calibration is relatively easy to correct by basing calibration on true protein nitrogen instead of total nitrogen.

Stabilisation of a protein prodrug formulation: a novel approach

APSAC (anisoylated plasminogen streptokinase activator complex) is a prodrug of the fibrinolytic lys-plasminogen streptokinase complex. Is is prepared by acylation of the serine hydroxyl group in the active centre of plasminogen, and is formulated as a freeze-dried powder for reconstitution and intravenous administration. The acyl group is labile in solution, and to a lesser extent also in the lyophilised state. Here we report a method for stabilising the prodrug by formulation with a water-soluble acylating agent. On reconstitution, any free hydroxyl groups formed during storage are rapidly reacylated while essentially full acylation is maintained for the required period in solution.