Biomedical subjects

Robert A Bellantone

Publications and source records attributed to Robert A Bellantone.

4 recordsLinked to original sources

PubMed2005

Measuring drug concentrations using pulsatile microdialysis: theory and method development in vitro.

A novel method of rapidly sampling drug concentrations, based on pulsatile microdialysis (PMD), was developed. In PMD, a dialysate fluid is pumped into a microdialysis probe, allowed to occupy the probe while at rest for some time, and then flushed at a high rate. A model that is based on a Fick's Laws was solved and tested, using methazolamide (MTZ) as the test drug in a variety of experimental setups, including time-dependent donor concentrations. Calibration plots of the donor versus sample concentrations were linear. There was excellent agreement between the calculated and experimental values of the fraction recovered obtained from the calibration plots. In a system for which the donor concentration declined in a first order manner, the data obtained using PMD and direct sampling of the donor were in nearly exact agreement with the theoretical value of k=0.09 min(-1). PMD was also able to collect data points quickly enough to characterize the rapid binding kinetics of MTZ by activated charcoal. It was concluded that PMD is an accurate method of sampling drug concentrations, and can obtain samples over shorter time intervals and more frequently than previously available methods.

Microdialysis↗

PubMed2002

Faster determination of membrane permeabilities without using the lag time method.

A new method of data analysis is presented that allows the determination of membrane permeabilities. The method is applicable to data obtained from a common experimental setup, in which drug dissolved in an inert donor gel diffuses through a membrane, initially void of drug, into a receiver for which sink conditions are maintained. The equations developed can also be used to predict the release of drug from these systems. Fick's Laws are solved, and the early time behavior of the mathematical solution is used to develop the analysis methods. Limitations of the model and their relations to experimental design are determined, and the method of application to experimental data is presented. The method is tested numerically using simulated data generated by a 1-d finite difference program that was used to numerically solve Fick's Laws, and also applied to in vitro human cadaver skin transdermal data for the drugs doxepin, imipramine and amitriptyline. It is concluded that this method can be applied to determine membrane permeabilities and diffusion coefficients with accuracy comparable to other experimental setups, such as lag time experiments and steady state experiments, but requiring experiments that can be significantly shorter.

Diffusion Chambers, Culture↗

PubMed2002

In vitro evaluation of the release of albuterol sulfate from polymer gels: effect of fatty acids on drug transport across biological membranes.

In this investigation, the diffusion of the beta 2 agonist albuterol sulfate (ABS) across several membranes (cellulose, hairless mouse skin, human cadaver skin) from polymer gels was studied, and the effects of several fatty acids on drug permeation through skin were evaluated. The results were then used to predict whether transdermal delivery would be appropriate for ABS. All in vitro release studies were carried out at 37 degrees C using modified Franz diffusion cells. In preliminary studies, ABS release through cellulose membranes was studied from two polymeric gels, Klucel (hydroxypropylcellulose) and Methocel (hydroxypropylmethylcellulose). Three polymer concentrations were used for each gel (0.5%, 1.0%, and 1.5%). From these experiments, Klucel 0.5% was selected as the optimal formulation to study ABS diffusion across hairless mouse skin. Experiments were conducted to evaluate the effects of capric acid, lauric acid, and myristic acid as penetration enhancers. The results suggested that lauric acid preferentially enhanced ABS diffusion compared to the other fatty acids studied, and follow-up studies were done to evaluate the release through human cadaver skin from a donor containing 2% ABS and lauric acid in 0.5% Klucel. These experiments showed that a 2:1 (lauric acid:ABS) molar ratio gave the best ABS release rates. The release rate across human cadaver skin declined slowly over 24 hr, and an average flux over 24 hr of approximately 0.09 mg/hr cm2 was measured. Using this value as a steady-state flux, extrapolations predicted that transdermal delivery can be used to maintain therapeutic ABS plasma levels (6-14 ng/mL) for extended periods. The results of this research suggest that ABS is a good candidate for transdermal drug delivery.

Albuterol↗

PubMedDate not supplied

Permeation study of five formulations of alpha-tocopherol acetate through human cadaver skin.

Alpha-tocopherol (AT) is the vitamin E homologue with the highest in vivo biological activity. AT protects against the carcinogenic and mutagenic activity of ionizing radiation and chemical agents, and possibly against UV-induced cutaneous damage. For stability consideration, alpha-tocopherol is usually used as its prodrug ester, alpha-tocopherol acetate (ATA), which once absorbed into the skin is hydrolyzed to alpha-tocopherol, the active form. The objective of this research was to characterize in vitro the permeation properties of ATA from various solutions and gel formulations. Permeation studies were conducted using modified Franz diffusion cells and human cadaver skin as the membrane. Specifically, 5% (w/w) alpha-tocopherol acetate was formulated in the following vehicles: ethanol, isopropyl myristate, light mineral oil, 1% Klucel gel in ethanol, and 3% Klucel gel in ethanol (w/w). The receiver temperature was 37 degrees C. Samples from the receiver were collected at 2, 4, 6, 8, 12, 24, 30, 36, and 48 hours and analyzed by HPLC for concentrations of alpha-tocopherol acetate and alpha-tocopherol. The permeabilities of ATA through human cadaver skin were 1.0x10(-4), 1.1x10(-2), 1.4x10(-4), 2.1x10(-4), and 4.7x10(-4) cm/h for the ethanol solution, isopropyl myristate solution, light mineral oil solution, 1% Klucel gel, and 3% Klucel gel, respectively. The results show that the formulation had relatively minor effects on the permeability coefficients of ATA through cadaver skin in all cases except for the isopropyl myristate solution.

Analysis of Variance↗