Moist-heat sterilization and the chemical stability of heat-labile parenteral solutions.

The impact of moist-heat sterilization (autoclaving) on the chemical stability of parenteral solutions was examined using two heat-labile products, clindamycin phosphate and succinylcholine chloride injections, as examples. A nonisothermal kinetic model was used to predict the extent of product degradation during autoclaving. The predicted results were found to be in close agreement with the experimental data.

Effect of postmolding heat treatment on in vitro properties of a polyanhydride implant containing gentamicin sulfate.

A polyanhydride implant containing gentamicin sulfate was fabricated using a laboratory-scale injection-molding machine. After injection molding, the implants were subject to heat treatment at 60 degrees C for various time periods with or without nitrogen protection. The impact of this heat treatment on the in vitro properties of the implants including copolymer molecular weights, mechanical properties, and in vitro drug-release profiles was investigated.

In vitro characterization of polyorthoester microparticles containing bupivacaine.

Laboratory-scale spray-congealing equipment was utilized to fabricate injectable microparticles consisting of polyorthoester and bupivacaine. Operating conditions for the spray-congealing process were optimized to produce microparticles with the desired shape and particle size to yield acceptable syringeability and injectability. Characterizations were performed to determine the chemico-physical properties of polyorthoester before and after microparticle fabrication.

Polyanhydride implant for antibiotic delivery--from the bench to the clinic.

A polyanhydride implant (Septacin) containing gentamicin sulfate was developed for sustained local delivery of the drug to the site of infection in the treatment of osteomyelitis. Laboratory-scale injection molding equipment was utilized to fabricate the implant for in vitro characterization. Molding conditions were optimized to produce implants with a skin-core structure which was found to be critical in preventing the initial cracking of the implant during in vitro drug release test in water.

The development of an injection-molding process for a polyanhydride implant containing gentamicin sulfate.

A production-scale manufacturing process has been developed for polyanhydride/gentamicin sulfate implants for the treatment of osteomyelitis. Gentamicin sulfate was first dried to an acceptable moisture level by using a tumble vacuum dryer. Dried gentamicin sulfate powder and polyanhydride granules were separately fed into the twin-screw extruder at a pre-determined metering rate using a gravimetric feeding device.

Development of a topical suspension containing three active ingredients.

The objective of this study was to develop a topical suspension that contains sarafloxacin hydrochloride (1 mg/mL), triamcinolone acetonide (1 mg/mL), and clotrimazole (10 mg/mL), and is stable at room temperature (15-28 degrees C) for clinical usage. Due to the difference in the physicochemical properties and chemical stability profiles of these three active ingredients, it is a challenge to develop a stable suspension formulation containing these three drugs. In this study, the stability of these drugs in different buffer solutions was determined under different accelerated isothermal conditions.

Effect of gamma-radiation on a polyanhydride implant containing gentamicin sulfate.

Septacin, a polyanhydride implant containing gentamicin sulfate, was sterilized by gamma-radiation. Its copolymer molecular weight (M(w) by GPC) was increased after this radiation. No cross-linking was shown in the radiated samples as no gel content was found by the filtration method.

The relationship between structures and in vitro properties of a polyanhydride implant containing gentamicin sulfate.

Laboratory scale injection-molding equipment was utilized to fabricate an implant consisting of poly(FAD:SA 1:1) and 20% (w/w) gentamicin sulfate. Characterizations were performed to determine the molecular weight and glass transition temperature of poly(FAD:SA 1:1). A study was carried out to investigate the relationships between the in vitro performance, morphology, and micro-structures of the molded implants.

Detection of Mycoplasma bovis in preservative-treated field milk samples.

Control of mycoplasmal mastitis requires individual cow milk sampling for culture and identification of Mycoplasma bovis. This sampling is time-consuming and expensive. Currently, some herds sample cows monthly with the dairy herd improvement (DHI) program, but a preservative is added to this milk that kills M.

Sevoflurance: approaching the ideal inhalational anesthetic. a pharmacologic, pharmacoeconomic, and clinical review.

Sevoflurane is a safe and versatile inhalational anesthetic compared with currently available agents. Sevoflurane is useful in adults and children for both induction and maintenance of anesthesia in inpatient and outpatient surgery. Of all currently used anesthetics, the physical, pharmacodynamic, and pharmacokinetic properties of sevoflurane come closest to that of the ideal anesthetic (200).

Determination of amylose/particulate relationship in hydroxyethylstarch.

Visual particulate was observed to form in parenteral hydroxyethylstarch over 24 months during stability studies. The particulate was identified as being amylose using FT-IR microscopy. Amylose values were measured in the bulk drug using the starch-iodine reaction.

Identification of a yellow impurity in aged samples of aqueous butamben suspension: evidence for the oxidative degradation of poly(ethylene glycol).

Butamben (butyl p-aminobenzoate) has been formulated to provide long-acting treatment for chronic pain. The suspension, which contains poly(ethylene glycol) and polysorbate 80, was found to yellow under ambient conditions if not adequately protected from oxygen. The impurity responsible for the color was isolated and identified on the basis of nuclear magnetic resonance spectroscopy and mass spectrometry.

Low-level (PPB) determination of cisplatin in cleaning validation (rinse water) samples. II. A high-performance liquid chromatographic method.

A high-performance liquid chromatographic (HPLC) method is described for the determination of residual levels of cisplatin from extracts of surfaces with very low surface area; from extracts of surfaces of coupons made of Teflon (polytetrafluoroethylene, PTFE), stainless steel, and glass; and in aqueous solution collected after rinsing equipment and parts. Initially, the method was developed to determine cisplatin at concentrations ranging from 20 to 200 ng/ml by direct injection. Retaining the same method conditions, the scope of the method was expanded by the addition of a sample preconcentration step, allowing analyses at levels ranging from 0.

Low-level (PPB) determination of cisplatin in cleaning validation (rinse water) samples. I. An atomic absorption spectrophotometric method.

Suitable analytical methods are required for quantitative determination of trace levels of ingredients in samples obtained for purposes of cleaning validation. We describe below an atomic absorption method for the quantitation of cisplatin, an antineoplastic agent, in aqueous samples. Cisplatin was reacted with diethyldithiocarbamic acid (DDTC), sodium salt, to yield a platinum-DDTC (Pt-DDTC) complex.

Investigation of the in vitro release of gentamicin from a polyanhydride matrix.

Septacin¿trade mark omitted¿ is a sustained release formulation consisting of gentamicin sulfate dispersed in a biodegradable polyanhydride matrix. The polyanhydride matrix is a copolymer of erucic acid dimer (EAD) and sebacic acid in a 1:1 weight ratio. In vitro drug release was performed in both water and pH 7.

A statistical experimental approach to cosolvent formulation of a water-insoluble drug.

19-Nor-1 alpha, 25-dihydroxyvitamin D2, an analog of vitamin D2, is a nonpolar compound with limited solubility in water. An injectable solution was formulated using a cosolvent system consisting of water, ethanol, and propylene glycol. A statistical response surface approach was used to evaluate the effect of these three solvents on the solubility of the drug (25 degrees C) in the ternary cosolvent system.

Light-scattering method in particle size analysis of parenteral emulsions.

The use of a light-scattering particle size distribution analyzer has been shown to be a convenient method for characterizing the particle size distribution of parenteral emulsions. However, the concentrations of the samples used were found to have a major impact on the particle size distribution results, particularly for samples with a mean particle size smaller than 0.2 micron.

Particle size determination of a flocculated suspension using a light-scattering particle size analyzer.

Microscopy is a useful and direct method for measuring the particle size of a suspension because, in addition to the particle size and size distribution, it provides visual detection of the shape and state of aggregation of the particles in the suspension. However, this method suffers from the shortcomings of being tedious and time consuming. In this study, a light-scattering particle size analyzer was used to determine the particle size and size distribution of a flocculated suspension.

Effect of hemodialysis on the pharmacokinetics of 19-nor-1alpha,25-dihydroxyvitamin D2.

The vitamin D2 analogue 19-nor-1alpha,25-dihydroxyvitamin D2 (paricalcitol) has been tested for the treatment of secondary hyperparathyroidism in patients with end-stage renal disease. Clinical studies have shown that paricalcitol reduces serum parathyroid hormone (PTH) levels with minimal potential to cause hypercalcemia, a common side effect of vitamin D3 therapy. Paricalcitol is typically administered intravenously after hemodialysis (HD).

Modeling of parenteral container headspace pressure.

When containers and related closure systems holding fluids are heated, internal pressures are generated. Depending upon conditions, surprisingly high pressures can be developed. These pressures are often sufficient to break system integrity.

The effect of closure processing on the microbial inactivation of biological indicators at the closure-container interface.

Two biological indicators are routinely used by the Hospital Products Division to demonstrate the sterilization of the closure-container interface. The use of a moist heat (Clostridium sporogenes) and a dry heat (Bacillus subtilis) biological indicator allows a better understanding of the parameters that impact sterilization of the closure-container system. The ability to sterilize a given closure-container interface is defined in large part by closure moisture and product time above 100 degrees C.

Analysis of sevoflurane degradation products in vapor phase samples.

Sevoflurane degradation products were measured by GC-flame ionization detection in vapor phase samples using manual and automated injection methods. Sample handling techniques allowed the transfer and storage of samples for up to 72 h. Compound A, fluoromethyl 2,2-difluoro-1-(trifluoromethyl)vinyl ether, was the major vapor phase degradation product formed in simulated clinical conditions.