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Biomedical subjects

D R Jenke

Publications and source records attributed to D R Jenke.

At least 19 recordsLinked to original sources
PubMed2001

Evaluation of model solvent systems for assessing the accumulation of container extractables in drug formulations.

The interaction between a medical device and a pharmaceutical solution it contacts may dictate solution safety and/or efficacy. Of specific concern is the ability of device components to leach into the contacting solution. As pharmaceutical solutions containing surfactants, co-solvents and solubilizing agents become more common, method's for assessing the extent of leaching are needed. In this manuscript, a model is developed which relates a solution's polarity to its ability to interact with a plastic material. The validity of the developed model is examined via direct analysis of several pharmaceutically relevant solutions.

Drug Compounding↗
PubMed1998

Development and validation of an ion-exclusion chromatographic method for the quantitation of organic acids in complex pharmaceutical products.

Effective quantitation of organic acids (acetic, malic, and lactic acids) present in total parenteral nutrition (TPN) pharmaceutical products for final product release purposes requires accuracy, precision, and specificity but less than optimal sensitivity. A chromatographic method relying on ion-exclusion separation and low-wavelength ultraviolet detection has been developed and validated to quantitate these organic acids in matrices containing 10-fold or greater excesses of other constituents (sugars, amino acids, and other inorganic salts) with no sample preparation other than dilution. Mobile phases at slightly different pH values effectively eliminates matrix-related interferences that were observed during the analysis of several products. The validation procedure used is discussed in terms of its strategy and results. Ultimately, the assay is found to be appropriate for the release testing of several compositionally diverse TPN products.

Acetates↗
PubMed1994

Drug binding by reservoirs in elastomeric infusion devices.

Drug binding by an elastomeric infusion device reservoir was assessed by measuring its ability to bind fifteen model solutes. Octanol/water (o/w) and hexane/water (h/w) partition coefficients were regressed against the reservoir's solute equilibrium binding constant to generate a binding model. The reservoir's drug binding ability was calculated with the model and drug partition coefficients, which were determined for seventeen commonly infused drugs including tobramycin, gentamicin, penicillin G, piperacillin, lidocaine, morphine, ceftriaxone, imipenem-cilastatin, amphotericin B, ticarcillin and clavulanate, pentamidine, vancomycin, foscarnet, desferoxamine, acyclovir, fluconazole and vinblastine. Formulations studied included 0.9% Saline and 5% Dextrose. With the exception of lidocaine, imipenem, vinblastine and fluconazole, octanol/formulation and hexane/formulation partition coefficients were too low to be measured for these drugs. Thus, the majority of the drugs, when reconstituted in 0.9% Saline or 5% Dextrose, will not be bound by the reservoirs. The magnitude of drug loss for the most highly bound species, fluconazole, is less than 2%. Therefore the reservoirs used in this study are essentially inert with respect to binding of the drugs evaluated in this study.

Binding Sites↗
PubMed1993

Evaluation of various solvent systems for modeling solute sorption with plasticized polyvinyl chloride materials.

The partitioning behavior of 16 chemically diverse model solutes was determined for four model solvents (octanol, hexane, heptane, and chloroform) and two components of plasticized polyvinyl chloride [PVC; PVC resin and dioctyl phthalate (DOP) plasticizer]. Interactions between these model solutes and four plasticized PVC polymers, differing in their PVC-to-DOP weight ratio, were studied. The data were used to evaluate the utility of the solvents and components to act as PVC interaction models (correlating the interaction constant of the plastic with the solvent-water partition coefficients of the solute). The ability of any single solvent to model the material-solute interaction was limited because of the multiple mechanisms by which the PVC and the solute can interact. Several bimodal solvent systems, including octanol and hexane, DOP and PVC resin, and octanol and heptane, mimic the behavior of polymers studied with a higher degree of accuracy. The success of these pairings is directly related to their ability to target different potential material-solute interaction mechanisms. The interaction properties of the test plastics are strongly impacted by the amount of plasticizer in the material. The interaction properties of the materials studied could be effectively represented as a mass-related average of the interaction properties of the major components of the material.

Absorption↗
PubMed1993

Modeling of solute sorption by polyvinyl chloride plastic infusion bags.

Methods for estimating the equilibrium and time-dependent sorption of solutes by polymeric containers have been developed. The methods are specifically applied to the sorption of solutes by polyvinyl chloride (PVC) infusion bags. The methods correlate the partition coefficients and dissociation constant (when appropriate) of the solute, the physical dimensions of the container, and solution pH with single parameters that dictate the shape of the sorption profile. To determine the equilibrium sorption level for PVC containers, the fractional binding of a solute is correlated with its hexane-water and octanol-water partition coefficients. Calculations based on single partition coefficients are less effective in terms of mimicking the behavior of the PVC. To determine the sorption profile (fractional binding versus time), the partition coefficients are related to the fraction binding at a particular time through a single parameter referred to as the sorption number. Equilibrium fractional binding and sorption profiles for various drugs stored in PVC containers are generated with the models and agree well with reported behavior. The effect of pH on the sorption process is also examined.

Adsorption↗
PubMed1993

Stabilization of oxygen-sensitive formulations via a secondary oxygen scavenger.

The ability to stabilize dopamine hydrochloride formulations via the utilization of a secondary bag containing an antioxidant has been established. By physically separating the drug formulation from the stabilization solution, the chemistry of both solutions can be optimized independently so as to ensure product efficacy. Factors controlling the effectiveness of the proposed stabilization strategy are discussed in the context of actual experimental results. Such a strategy is effective in terms of protecting the formulation during processing/storage only if the product is stored in an oxygen barrier overpouch.

Buffers↗
PubMed1992

Drug delivery via ion exchange across a micromembrane.

The exchange of pharmaceutically significant amounts of dopamine across a micromembrane is reported, establishing the practical basis for such a drug delivery system. Drug release was accomplished with a commercially available device initially intended for use as a postcolumn reactor in ion chromatography. Release of other ionic drugs (e.g., methyldopate and piperacillin) was also achieved but with a lesser efficiency than was dopamine, presumably because of a size effect. The effect of releasing ion identification and concentration, the flow rate of the delivery solution and concentration of drug in the device reservoir on the drug release efficiency was examined. Under optimal conditions the efficiency approaches 80%, and 1 mg of drug is released/ml of delivery solution. Alternatively, operating conditions can be changed so that magnitude of release is optimized but absolute efficiency is sacrificed. Under such conditions the magnitude of dopamine release approaches 2 mg/ml but exchange efficiency is approximately 25%.

Chromatography, High Pressure Liquid↗
PubMed1991

Effect of solution phase composition on the interaction between aqueous model solutes and polymeric container materials.

The interaction between several marker solutes and a polyolefin laminate polymer was studied in several solutions. Solutions studied included mixtures of sodium chloride and dextrose (at concentrations more less typical of i.v. administration solutions) and several actual i.v. products [lactated Ringer's injection, Dianeal, Travasol (amino acid) injection, and alcohol/dextrose injection]. The interaction properties of the candidate container material correlated well with the solute's octanol-water partition coefficient. For nonionic species, the magnitude of the container/solution interaction was independent of solution phase composition. For the ionic test solute, solution pH, which impacts the speciation of the solute, was the only solution composition variable that significantly influenced the interaction. Thus water (or a weak buffer solution) is suggested as an appropriate model solvent for use in container compatibility evaluations involving i.v.-related products.

Chromatography, High Pressure Liquid↗
PubMed1990

Influence of solute degradation on the accumulation of solutes migrating into solution from polymeric parenteral containers.

Solute stability in solution, in addition to solute-polymer interaction properties and the total solute available pool, impacts the interaction between a polymeric container and a parenteral product, specifically in terms of the migration of trace polymer components into the contained solution. A specific solute/polymer system has been studied with respect to properties impacting the magnitude and rate of solute migration from the polymer into solution. The solute, an alkyl ester, originates in a polyolefin composite packaging material. Solute degradation kinetics were studied as a function of solution temperature and pH. Solute-polymer interaction properties including the equilibrium binding constant and diffusion coefficient were obtained. An accumulation rate model is developed for the determination of the solution phase concentration of the liberated solute as a function of storage time and conditions. Coupling the model with the properties of the polymer-solute system studied provides a tool that accurately predicts solute accumulation behavior in a representative parenteral product configuration.

Drug Packaging↗
PubMed1990

Determination of solute-polymer interaction properties and their application to parenteral product container compatibility evaluations.

Kinetic and thermodynamic interaction properties between dialkyl phthalate test compounds and a polyolefin polymer were examined via a permeation-cell experimental design. Disappearance and appearance rates of solute in the receptor and donor solutions, as well as the equilibrium composition of the test system, are used to determine sorption and diffusion coefficients and the solute/polymer equilibrium binding constant. Sorption rate constants and diffusion coefficients exhibit Arrenhius-type behavior. The binding constants obtained correlate well with the solute's octanol-water partition coefficient. The kinetic and thermodynamic data generated combine with proposed interaction models to identify solute/polymer interactions (binding and leaching) pertinent to evaluating container/solution compatibility for parenteral products.

Diffusion↗
PubMed1989

Drug stability testing by monitoring drug and degradate levels by liquid chromatography.

A cephalosporin antibiotic and its primary degradation product can be separated by a mixed retention mechanism using an ion exchange column and a mobile phase containing acetonitrile and aqueous sodium phosphate. Assay ruggedness, specificity, linearity of response, and standard-sample stability are evaluated and found to be adequate for the desired application. Drug degradation at room temperature in formulations containing citrate and dextrose is found to be roughly first order; fit of the first order rate expression model is better when gain in degradate levels is used as opposed to the direct measurement of drug loss, especially when the magnitude of drug loss is small. The greater accuracy of projections based on the measurement of degradate gain is related to the effect of the imprecision of the analytical measurement on the accuracy of the model.

Chromatography, High Pressure Liquid↗
PubMed1988

On-line sample cleanup in the liquid chromatographic analysis of pharmaceuticals for citrate content.

Matrix interferents are removed from pharmaceutical samples via an on-line, automated column switching process in which the difference in hydrophobicity between the analyte and the interferents allows these species to be isolated in different parts of the chromatographic system. In this case, the interferents are trapped on a cleanup column and are flushed to waste as the analyte undergoes additional separation on an analytical column. The utility of this approach is demonstrated by the quantitation of citrate in pharmaceutical samples by ion suppression, reversed-phase liquid chromatography. The performance of this system is statistically equivalent to that of a manual pretreatment method employing disposable, solid-phase extraction cartridges.

Chromatography, Liquid↗
PubMed1987

Determination of trace levels of oxytocin in pharmaceutical solutions by high-performance liquid chromatography.

A high-performance liquid chromatographic assay has been developed for quantitating oxytocin in common large volume parenteral intravenous solution matrices. Separation is accomplished by a reversed-phase mechanism using a C18 column. The analyte is detected fluorimetrically after post-column derivatization with fluorescamine. Reaction efficiency is controlled by the use of a reaction buffer which is added separately from the fluorescamine via a dual pump reactor system. Given the low analyte concentration [40 parts per billion (10(9)) or less], the samples are concentrated on-line through the use of a trapping column and switching valve. To improve productivity, pre-concentration and analysis of adjacent samples is timed to occur concurrently. Performance of the assay is characterized by a high degree of accuracy, precision and ruggedness; the system is capable of distinguishing between the analyte, matrix components, impurities and common degradates.

Chromatography, High Pressure Liquid↗
PubMed1987

Determination of alcohols in pharmaceuticals by ion-exclusion chromatography.

Alcohols present in pharmaceutical intravenous solutions (e.g. propylene glycol and ethanol) are separated from each other and common matrix components by an ion-exclusion column with a dilute sulfuric acid mobile phase. Using refractive index detection, the assay is characterized by an absolute detection limit of 1 ng and a linear dynamic range for both area and height which spans three orders of magnitude. Chromatographic ruggedness is sufficiently high so that strict system suitability criteria can be met even after 600 injections have been made. Long-term detector stability is enhanced through the use of a flowing reference cell.

Alcohols↗