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Biomedical subjects

J W Mauger

Publications and source records attributed to J W Mauger.

At least 19 recordsLinked to original sources
PubMed2004

Dissolution of anecortave acetate in a cylindrical flow cell: re-evaluation of convective diffusion/drug dissolution for sparingly soluble drugs.

Steady-state drug release rates were measured from a model cylindrical implant, comprised mainly of the sparingly soluble drug anecortave acetate, suspended as an obstacle in a cylindrical flow cell. Dissolution medium was delivered at a steady, slow flow rate (0.05-0.7 mLs/min) using an HPLC pump, and samples from the outflow were analyzed by direct injection onto an HPLC column. Release rates were determined as a function of flow rate for three different implant orientations--vertical, elevated to the center of the dissolution cell; horizontal, elevated; and horizontal, resting directly upon the flat porous inlet frit. Release rates were ranked as follows: horizontal, floor >> horizontal, elevated>vertical, elevated. The steady, laminar flow enabled use of the finite element method (FEM) to simulate the dissolution process using convective diffusion/drug dissolution theory. Simulations predicted the absolute magnitude of the release rate to within < 10% for all situations, and predicted the power law exponent of the dependence of release rate on flow rate with great accuracy. The current method is more general than compendial methods that provide a dissolving surface that is uniformly accessible to the dissolution medium, or a shear rate that is uniform across the entire dissolving surface. The current approach may be utilized to provide estimates of dissolution rates for any geometry and set of hydrodynamic conditions that can be numerically calculated.

Algorithms↗
PubMed1998

Creating a team approach to hospital and college of pharmacy relationships: a strategy to integrate missions to enhance education and patient care.

Academic medical centers continue to bear the burden of the additional costs of professional education. Such institutions and their affiliated colleges of pharmacy are challenged to sustain the degree of professional staffing required to deliver quality education and patient care services. Historically, these relationships have not always proven to be cooperative and mutually beneficial. As managers and deans attempt to maximize the productivity of their financial and human resources, they will need to creatively structure relationships that effectively meet those diverse professional missions that sometimes seem to exist in conflict or that each seem to be successful only at the expense of the other. Pharmacists who act as both faculty, delivering experiential education, and clinical staff providing patient care, are significantly stressed in their attempts to meet the sometimes conflicting objectives of these multiple missions. The survival of precepted experiential education in pharmacy and of pharmaceutical care in academic medical center hospitals will likely depend upon a model of cooperative relationship, such as the venture described by Jorgenson, et al.

Academic Medical Centers↗
PubMed1995

Controlled release of substituted benzoic and naphthoic acids using Carbopol gels: measurement of drug concentration profiles and correlation to release rate kinetics.

PURPOSE: The objective of this study is to correlate drug release mechanism with measured drug concentration profiles in gel layers of Carbopol matrices containing mesalamine or benzoic acid. METHODS: Release rate experiments with Carbopol matrices were performed using a rotating disk apparatus. Matrices were frozen and the gel layer in the matrices was sliced using a microtome in a cryostat. Drug concentration profiles were determined by direct measurement of the concentration of the drug in the gel slices. The pH of the slices was measured using microelectrodes, and water content was measured by Karl Fisher titration. RESULTS: The concentration gradient in mesalamine matrices decreased over time and correlated with square root of time release rate kinetics. The concentration profiles of benzoic acid were unchanged over time and correlated with zero order release rate kinetics. Carbopol gel layers were highly hydrated (93-95% water). Gel layers in matrices with mesalamine had a more alkaline microenvironmental pH. This higher pH resulted in increased growth of the thickness of the gel layer and a reduction drug diffusivity in comparison to benzoic acid matrices. CONCLUSIONS: The release rate kinetics of mesalamine and benzoic acid correlated to the measured concentration profiles. The shape of the concentration profiles is determined by the rate of growth of the Carbopol gel layer and drug diffusivity.

Acrylic Resins↗
PubMed1993

Lack of inhibition of adhesion of an enteropathogenic Escherichia coli by polycarbophil.

Anionic polyacrylic acid polymers, such as polycarbophil, have a number of properties that would make them suitable carriers for sustained antibiotic release formulations in the intestinal tract. However, little is known with regards to possible microbial adhesion to polycarbophil. The aim of this study was to evaluate for such an interaction using the rabbit enteric pathogen Escherichia coli RDEC-1 (serotype O15:H-). RDEC-1 mediates attaching and effacing binding to intestinal epithelium in a manner morphologically identical to that observed in both human enteropathogenic E. coli and enterohemorrhagic E. coli infections. RDEC-1 bacteria were grown to promote the expression of the mannose-resistant AF/R1 adhesion pili. A nonpiliated mutant, strain M34, was used as a negative control. Using radioactive labeling of bacteria, we quantitated adhesion of piliated RDEC-1 in the presence of polycarbophil using an in vitro adhesion assay system. Binding of piliated RDEC-1 in the adhesion assay was greater than for nonpiliated M34 for all concentrations of bacteria greater than 10(9) (P < .05). Polycarbophil did not cause concentration-dependent inhibition of piliated RDEC-1 binding (P > .05). We conclude polycarbophil does not interfere with the AF/R1 adhesin ligand of RDEC-1. Use of this polymer as a mucoadhesive drug delivery vehicle for nonabsorbable antibiotics in the treatment of gastrointestinal infections would not be expected to interfere with the protective effects of intestinal mucins.

Acrylic Resins↗
PubMed1993

Evaluation of the physicochemical properties and dissolution characteristics of mesalamine: relevance to controlled intestinal drug delivery.

The physicochemical properties of mesalamine and the effect of pH and buffer concentration on the dissolution rate of pure mesalamine and mesalamine with Carbopol 974P were investigated. The aqueous solubilities at 25 and 37 degrees C were 0.844 and 1.41 mg/mL, respectively. Consistent with the observed pKa1 (2.30) and pKa2 (5.69) or mesalamine, the solubility-pH profile is increased at pH < 2.0 and pH > 5.5 and is minimized from pH 2.0 to pH 5.5. The flux data were consistent with the solubility data from pH 1.0 to pH 5.5. The flux increased and plateaued at pH values 5.5 to 7.0 and was dependent on the bulk buffer concentration. At low bulk buffer concentrations, mesalamine reduces the pH in the diffusion layer, which results in a decrease in flux. The medium with the highest buffer capacity has a greater ability to increase the surface pH and dissolution rate. The addition of Carbopol reduces the flux and the sensitivity of the dissolution rate of mesalamine to increasing bulk buffer concentration. This reduction is postulated to be due to neutralization of the basic dissolution media, gel formation, and possible drug-polymer interactions.

Acrylic Resins↗
PubMed1991

Drug delivery systems.

New and emerging drug delivery systems for traditional drugs and the products of biotechnology are discussed, and the role of the pharmacist in ensuring the appropriate use of these systems is outlined. Advantages of advanced drug delivery systems over traditional systems are the ability to deliver a drug more selectively to a specific site; easier, more accurate, less frequent dosing; decreased variability in systemic drug concentrations; absorption that is more consistent with the site and mechanism of action; and reductions in toxic metabolites. Four basic strategies govern the mechanisms of advanced drug delivery: physical, chemical, biological, and mechanical. Oral drug delivery systems use natural and synthetic polymers to deliver the product to a specific region in the gastrointestinal tract in a timely manner that minimizes adverse effects and increases drug efficacy. Innovations in injectable and implantable delivery systems include emulsions, particulate delivery systems, micromolecular products and macromolecular drug adducts, and enzymatic-controlled delivery. Options for noninvasive drug delivery include the transdermal, respiratory, intranasal, ophthalmic, lymphatic, rectal, intravaginal, and intrauterine routes as well as topical application. Rapid growth is projected in the drug delivery systems market worldwide in the next five years. Genetic engineering has mandated the development of new strategies to deliver biotechnologically derived protein and peptide drugs and chemoimmunoconjugates. The role of the pharmacist in the era of advanced drug delivery systems will be broad based, including administering drugs, compounding, calculating dosages based on pharmacokinetic and pharmacodynamic monitoring, counseling, and research. The advent of advanced drug delivery systems offers pharmacists a new opportunity to assume an active role in patient care.

Administration, Oral↗
PubMed1988

Dissolution rate studies from a stationary disk/rotating fluid system.

The dissolution rates for hydrocortisone alcohol and acetate were determined using a stationary disk/rotating fluid system. The hydrocortisone was compressed in a tablet die, and the die placed in a vessel above a rotating magnetic bar. Dissolution rates were evaluated in aqueous media under conditions involving the following independent variables: solubility (Cs), diffusion coefficient (D), viscosity (v), rotational speed (omega), and tablet radius (r). A design equation which relates dissolution rate (R) to these variables was formulated for the system R alpha Cs D2/3 (v) -1/6(omega)1/2(r)3/2 This design equation adequately represents the system, which is related to fluid mechanics and convective diffusion models. The fluid mechanics model assumes that the fluid ideally rotates as solid-body rotation and the momentum layer is initiated at the outside radius of the tablet die. The convective diffusion model is based on the formation of a diffusion layer at the outside radius of the dissolving surface and a predictable relationship between the momentum and the mass transport quantities of bulk viscosity and diffusion coefficient. This configuration, like the rotating disk in a stationary fluid, offers the attractive attribute of being useful to study drug release mechanisms for systems of pharmaceutical interest.

Chemistry, Pharmaceutical↗
PubMed1983

Dissolution profiles for finely divided drug suspensions.

A suspension of micronized prednisolone acetate was separated into four fractions by the technique of centrifugal elutriation. Data showed that each fraction had a narrow particle size. The dissolution experiments were carried out under sink conditions (less than 10% of saturation concentration) in a dissolution apparatus with a rotating filter assembly and a continuous circulation of filtered fluid samples through a recording spectrophotometer. The dissolution profile was highly reproducible and substantially different for each fraction. As expected, fractions with the smallest and largest particles showed the fastest and slowest dissolution, respectively. Almost the entire dissolution profiles for four small particle size fractions can be satisfactorily described by the Higuchi-Hiestand model with the dissolution rate constant, K, in the range of 1.5-2.0 X 10(-9)cm2/sec. This is approximately 3.5 times greater than the value for K calculated on the basis of reported reasonable values for diffusion coefficient, density, and solubility.

Models, Theoretical↗
PubMed1979

Hydrodynamic characterization of a spin-filter dissolution device.

The spin-filter dissolution device was characterized using a two-dimensional convective diffusion model. Experimental model testing involved analysis of dissolution rates from nondisintegrating salicylic acid disks. The disks were prepared as double-layer tablets, with an ethylcellulose layer as a nondissolving surface. For each dissolution run, the disk was positioned so that the dissolving salicylic acid surface was parallel to the flow of the circulating fluid. Experimental variables included the stirring speed, the tablet radius, and the distance of the tablet from the stirring source. At the farthest distance from the stirring source, the average numerical exponents for stirring speed and tablet radius were 0.58 and 1.54, respectively, which compare favorably with the values of 0.50 and 1.50 from the model. When the dissolving salicylic acid surface was positioned closer to the stirring source, the numberical exponent for the stirring speed increased significantly, while the average numerical exponent for the tablet radius was lowered to 1.07, indicating a change is dissolution mechanism as a function of distance from the stirring source. These data indicate that dissolution rates are not necessarily proportional to surface area as predicted by the Nernst equation and that distance from the stirring source is significant.

Chemistry, Pharmaceutical↗
PubMed1979

Tablet position and basket type effects in spin-filter dissolution device.

The effects of stirring and basket placement on tablet dissolution using the previously developed Shah spin-filter device were investigated. Visualization of flow and dissolution patterns was possible by testing nondisintegrating colored tablets. Dissolution experiments were conducted on nondisintegrating double-layered tablets containing salicylic acid as the dissolving layer and ethylcellulose as an inert nondissolving layer. Visual observations revealed that color was drawn more rapidly from the tablet face resting on the bottom of the basket. Dissolution data from multilayered tablets revealed that when the salicylic acid face was resting on the bottom of the basket, the dissolution was appreciably more rapid than when it was facing up in the basket. This phenomenon was found for several stirring speeds.

Diffusion↗
PubMed1978

Thermodynamics of aqueous solutions of parabens.

The solubility of a related series of parabens was determined in water at four temperatures. The parabens chosen were the methyl through n-butyl p-hydroxybenzoates, and the temperature variations were 5 degrees increments from 25 to 40 degrees. These solutes are useful preservatives, especially combinations of the methyl and propyl ester derivatives. The chemical relationship of these compounds varied by successive linear methylene additions on the ester portion of the molecules. The thermodynamic values obtained for these aqueous systems could be related to these molecular variants since the remainder of the molecule was constant. For the overall thermodynamics, the free energy functions such as the ideal, actual, and excess were found to be smooth, nonlinear functions of the number of carbon atoms in the alkyl portion of the paraben esters. A linear relationship with the number of carbon atoms in the ester portion of these esters was found with the partial excess free energy of the solute.

Parabens↗
PubMed1978

Separation of multisized drug suspensions into narrow distributions by centrifugal elutriation.

A centrifugal elutriator rotor was used to separate suspensions of micronized hydrocortisone acetate and prednisolone acetate. Up to five distinct particle fractions could beisolated from a single parent suspension, and reasonable reproducibility was exhibited between various elutriator runs. Arithmetic means and associated standard deivations, based on volume, were calculated for each isolated fraction. These data demonstrate the narrowness and uniqueness of each fraction. The particle-size data show an apparent log-normal distribution for each isolate. The uniqueness of each fraction also was demonstrated by dissolution experiments where Fraction 1, the smallest fraction of prednisolone acetate, dissolved much more rapidly than Fraction 4, the largest fraction. The substantial difference in dissolution behavior of these two fractions of prednisolone acetate powder was biopharmaceutically significant.

Centrifugation↗
PubMed1977

Solubility profiles and thermodynamics of parabens in aliphatic alcohols.

The solubility of a series of compounds was determined in a wide polarity spectrum of normal aliphatic alcohols over a limited temperature range. The solutes chosen were the methyl through n-butyl p-hydroxybenzoates, several of these being useful preservatives. Solubility profiles were determined for these compounds, and the effect of temperature upon their solubility behavior was investigated. The solubility of the solutes is expressed in several concentration notations; mole fraction plots showed a variable twin peak array as a function of the dielectric constant for the solutes studied. Since heats of fusion were available and data were generated as a function of temperature, thermodynamic parameters for these systems could be calculated. The relationship of these parameters to multiple solubility peak array is discussed.

Alcohols↗
PubMed1977

Dissolution profile for multisized drug particles: new approximate expression.

New approximate expressions for the weight fraction undissolved were obtained using the Taylor series expansion. These approximations were tested using simulated data for multisized drug particle populations. The resulting calculations show that: (a) the approximations are not dependent on a knowledge of the analytical form of the particle-size density function, (b) the distribution effects are accounted for, but only a knowledge of the sample mean and standard deviation is required, and (c) the approximations (especially on a weight basis) lead to values within the limits of error in dissolution studies, thus posing the question of whether published exact experessions have practical value.

Chemistry, Pharmaceutical↗
PubMed1977

Dissolution profiles for multisized prednisolone acetate suspensions.

Particle-size measurements and in vitro dissolution characteristics of commercial and formulated suspensions of prednisolone acetate were determined using a resistance particle counter and a spinning filter apparatus, respectively. Significant differences in dissolution rates were noted for the commercial suspensions. Particle size affected dissolution but did not account for all observed variations in the dissolution rate. Formulation differences, specifically the presence of hydroxypropyl methylcellulose, in suspensions seemed to be important in dissolution.

Chemistry, Pharmaceutical↗
PubMed1976

Solubility of straight-chain and branched alkyl barbiturates in straight-chain alcohols.

The solubilities of a series of chemically related barbiturates, including some medically useful ones as well as phenobarbital, were determined at 25 degrees in the straight-chain alcohols methanol through butanol. The solubility values are given in both milligrams per milliliter and the mole fraction notation. The solubility in methanol was the highest and decreased nonlinearly for the solubility in 1-butanol. In several cases, mole fraction solubility gave shouldering or peaking as a function of the carbon number of the solvent. This series of barbiturates was broken down into two subsets of straight-chain and branched alkyl barbiturates, and solubility ratios in these subsets were considered.

Alcohols↗