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Biomedical subjects

C T Rhodes

Publications and source records attributed to C T Rhodes.

At least 19 recordsLinked to original sources
PubMed1991

An evaluation of ibuprofen bioinversion by simulation.

Using a pharmacokinetic model recently proposed to explain ibuprofen disposition in man, plasma concentrations of pure ibuprofen enantiomers were simulated following oral administration of (-)-(R)-ibuprofen, (+)-(S)-ibuprofen, or rac-ibuprofen. Simulated and literature values for AUC's were used to compare S/R ratios for different cases of the model and for different methods of calculating the fraction of R bioinverted to S. Numerical simulation using STELLA confirmed previous results for different cases of bioinversion. Simulated S/R AUC ratios, for administration of the racemate, ranged from 4.0 (presystemic bioinversion) to 1.66 (systemic bioinversion). Literature values for S/R AUC ratios averaged 1.53 +/- 0.2 for administration of the racemate; therefore, systemic bioinversion was concluded to be representative of ibuprofen disposition. Additional simulations of S/R AUC ratios, for administration of (-)-(R)-ibuprofen only, ranged from 1.5 (presystemic bioinversion) to 0.66 (systemic bioinversion). Literature values for S/R AUC ratios averaged 0.50 +/- 0.9 for administration of (-)-(R)-ibuprofen only, which again supported conclusions of systemic bioinversion. Using different equations for estimation of fraction of R inverted to S (FR----S), results based on simulated data were identical; however, FR----S values based on literature data were different. Therefore, assumptions made for different FR----S equations do not appear to be rigorous. Calculations of FR----S, based on literature data, averaged 0.52 overall, indicating bioavailability of (+)-(S)-ibuprofen may be similar for a 150 mg dose of (+)-(S)-ibuprofen compared to a 200 mg dose of racemate.

Humans↗
PubMed1991

The design of analytical methods for use in topical epidermal growth factor product development.

Data from a reverse phase gradient elution HPLC assay for human epidermal growth factor (EGF) was compared and correlated with data obtained from a competitive heterogeneous radioimmunoassay (RIA). The RIA was established to measure very low concentrations of EGF in formulation drug release and compatibility studies. The HPLC assay, capable of resolving parent and possible modified or fragmented forms of EGF isolated from human urine, was studied as a potential development tool for stability and final product evaluation. As independent analytical methods, the HPLC and the RIA procedures produced correlated results when quantifying freshly prepared and certain degraded samples of EGF. The capacity of the HPLC method to serve as a stability indicating assay was examined. Degradation of EGF was induced by storage in 0.05 M phosphate buffer pH 7.4 at 25, 37 or 50 degrees C. The same three degradation products were detected at each temperature by the HPLC method, one of which was identified as L-isoaspartyl EGF.

Amino Acids↗
PubMed1991

Influence of different sources on the processing and biopharmaceutical properties of high-dose ibuprofen formulations.

It is known that depending on the manufacturing and synthetic processes, drugs may exist as different forms. As a result, physicochemical properties, compression characteristics, intrinsic dissolution and bioavailability may vary substantially. The purpose of this study was to investigate the effect of different sources of ibuprofen on the processing of tablets and on their properties. Another emphasis of this work was to rationalize one or several key characteristics of the raw material as directly related to wet granulation parameters and to the behavior of final tablets. Commercially available ibuprofen was obtained from different manufacturers and a preformulation program, including X-ray crystallography, differential scanning calorimetry, scanning electron microscopy, determination of particle size distribution and flowability, was performed to characterize the raw material. Granules were prepared with a planetary mixer and liquid requirements for the end point were obtained by monitoring power consumption. Tablets were manufactured on Stokes rotary and single punch instrumented presses. Data acquisition interfaces produced compression data for each formulation. Granules and final tablets were analyzed for hardness, dissolution profiles and content uniformity. Statistical evaluations using analysis of variance and multiple comparison procedures were performed on the results to determine the significance of the variability between independent parameters. The ibuprofen tested was found to be a unique polymorphic form with some differences in the external crystallinity. The particle size characteristics of the material also allowed a differentiation between sources and although there was no differences in dissolution patterns or content uniformity, particle size was found to account for 50% of the variability in tablet hardness. Two sources of ibuprofen with lower mean particle size showed significant variations in end point liquid requirements resulting in variable tablet crushing strength.

Biopharmaceutics↗
PubMed1991

Investigations of epidermal growth factor in semisolid formulations.

Three simple formulations, with various physicochemical characteristics, were designed as potential pharmaceutical bases for delivery of epidermal growth factor (EGF) to open wounds. The compatibility of EGF with formulation excipients and the release of EGF from each formulation were evaluated in vitro using a release cell apparatus. Samples were analyzed by competitive heterogeneous radioimmunoassay. The apparatus and procedures used in the study were validated to ensure EGF stability during the study, and to verify the absence of excipient interference with analytical procedure. Batches of Pluronic F-127 25% gel formulation and Carbopol gel formulation showed similar average EGF release rates of 17.12 and 16.55 micrograms/cm2/hr, respectively. A vanishing cream formulation similar to the commercial product Silvadene showed much slower release of 0.5 microgram/cm2/hr.

Chemistry, Pharmaceutical↗
PubMed1979

Systemic absorption of topical salicylic acid.

The systemic absorption of salicylic acid in humans following topical application in either hydrophilic ointment or polyethylene glycol 400 vehicle was studied. Drug absorption was minimal following application to intact skin; however, measurable levels (8 mg/dl) were attained when the stratum corneum was removed prior to application of the drug in hydrophilic ointment. A one-compartment open model with first order absorption and elimination processes was fitted to the plasma salicylate concentrations as a function of time. Computer simulations predict that plasma salicylate levels associated with toxicity in some patients may be present after repetitive application of the drug in hydrophilic ointment.

Adult↗
PubMed1978

Potential of liquid membranes for drug overdose treatment: in vitro studies.

The in vitro removal of six barbiturates from pH 2 donor solutions by liquid membranes with pH control was evaluated. More than 90% of amorbarbital, phenobarbital, and secobarbital were removed within 10 min by the liquid membranes. Drug transport obeyed first-order kinetics initially, and Fick's law was obeyed. The transport rate of phenobarbital by a liquid membrane was temperature dependent. An Arrhenius plot revealed that the activation energy was 10 kcal/mole. The liquid membranes showed some instability in the presence of bile salts.

Barbiturates↗
PubMed1977

Solubility and ionization characteristics of phenytoin.

The solubility of phenytoin was determined in pH 7.4 and 5.4 phosphate buffers at five temperatures; in hydroalcoholic solutions, 0--4% methanol; and in pH 4.8--8.4 buffer solutions. From the temperature data, the enthalpy and entropy of solution of this nonideal system were calculated and were similar at both pH values. The data obtained from the buffer solutions were used to calculate the apparent dissociation constant, pKa', of phenytoin as 8.06. A GLC method with on-column methylation was used to quantitate phenytoin with 5-(p-methyl-phenyl)-5-phenylhydantoin as an internal standard. The assay uses chloroform of extraction of the drug from aqueous solutions. The ratio of peak heights was adjusted for weights of aqueous and organic layers, and results were calculated in micrograms per gram of sample and mole fraction of phenytoin. Although hydroalcoholic solutions enhanced drug solubility, there is a potentially significant disadvantage in using alcohol for clinical studies.

Chemical Phenomena↗
PubMed1977

Aging of tablets made with dibasic calcium phosphate dihydrate as matrix.

The aging of direct compression tablets made using dibasic calcium phosphate dihydrate as the tablet matrix was investigated over 16 weeks. The formula included 6% amaranth as a dye tracer. Two sets of stress storage conditions were used: 25 degrees and 50% relative humidity and 45 degrees and 75% relative humidity. Tablets were evaluated periodically by visual inspection; determination of the weight of 10 separate tablets, the size of 10 tablets measured by a micrometer screw gauge, and the hardness of 10 tablets as indicated by a Strong-Cobb hardness tester; the USP disintegration time test; and the USP dissolution test. Tablets stored at 25 degrees and 50% relative humidity showed an approximately linear increase in disintegration and dissolution time over 16 weeks with no other significant changes. Storage at 45 degrees and 75% relative himidity resulted in significant changes in most measured parameters; tablets showed blotching, substantial weight loss, and complex changes in disintegration and dissolution. The changes at elevated temperatures are related to loss of water of hydration; changes at 25 degrees must be due to other causes.

Calcium Phosphates↗
PubMed1976

Development of a stable sublingual nitroglycerin tablet II: formulation and evaluation of tablets containing povidone.

Stable and pharmaceutically elegant sublingual nitroglycerin tablets were formulated using povidone to retard volatilization of the drug. Formulation and processing variables were investigated to produce an acceptable product. A blend of two grades of povidone, of different degrees of cross-linkage and water solubility, provided stable tablets which exhibited rapid disintegration. Directly compressed sublingual tablets made in this study retained over 80% of the initial nitroglycerin when exposed to the atmosphere at room temperature for 2 months. The direct compression tablets are of good appearance and low friability, and the formulation is readily compressed without problems. An interesting relationship among the hardness, disintegration time, and compaction pressure is described.

Drug Compounding↗
PubMed1976

Improved transport apparatus for examining diffusion of drugs across isolated tissues and synthetic membranes.

A three-compartment diffusion apparatus that can accommodate synthetic as well as small isolated biological membranes such as rat intestine was developed and tested. The diffusion of drug from two outer donor cells into a central recipient cell allows for more membrane surface exposure and greater sensitivity in assaying as compared with previously published techniques. Reproducibility values for the synthetic membrane were equivalent to those obtained in more elaborate designs, while the reproducibility for biological membranes compared favorably with everted gut preparations and a similar diffusion apparatus. The clearance, per square centimeter of membrane, of salicylamide at pH 7.4 and 37 degrees was 0.288 ml/hr/cm2, which agreed with previous literature reports of different techniques. Although the diffusion through a synthetic membrane was more rapid, introduction of a nonionic surfactant enhanced the biological perfusion rate while having no significant effect on the synthetic barrier. The enhancement of the diffusion rate effected by 0.1 and 0.01% (w/v) surfactant was about twofold, rapid in onset, and not progressive, giving clearance values per square centimeter of 0.606 and 0.537 ml/hr/cm2, respectively.

Animals↗
PubMed1976

Effect of storage at specified temperature and humidity on properties of three directly compressible tablet formulations.

Direct compression tablets containing sodium starch glycolate, an alginate derivative, or povidone as a disintegrant, magnesium stearate as a lubricant, amaranth as a tracer, and dibasic calcium phosphate dihydrate as the matrix were stored for 30 days at 23 degrees and 75% relative humidity (R.H.), 45 degrees and 75% R.H., and 65 degrees and 40% R.H. Samples were evaluated after 0, 10, 20, and 30 days for size, hardness, and dissolution characteristics. Although no significant changes in the dimensions or hardness of the three tablet formulations, prepared at three different compaction pressures, were observed, the dissolution efficiency of the systems showed significant changes, some systems dissolving more rapidly and some more slowly after storage. In some cases, the changes were so substantial as to indicate the possibility of significant changes of the bioavailability of drugs formulated in such systems. The relevance of this work to the problem of evaluating aging effects on the physical properties of tablets is discussed.

Drug Stability↗
PubMed1976

Effect of variation in compaction force on properties of six direct compression tablet formulations.

The effect of variation in compaction force on six direct compression tablet matrixes was investigated. An instrumented tablet press allowed direct measurement of applied and ejection forces. Hardness, apparent tablet density, and disintegration times also were determined. The disintegration time of spray-dried lactose tablets was essentially independent of compaction force. However, in the other systems investigated, the properties studied showed varying types of dependence on compaction pressure. A direct compression formula was developed and exhibits a decrease in disintegration time as compaction force is increased.

Chemistry, Pharmaceutical↗