Alan E. Polack

The effect of iontophoresis and vehicle pH on the in-vitro permeation of lignocaine through human stratum corneum

The effect of iontophoresis and the pH of aqueous vehicles on the rate and extent of permeation of lignocaine through excised human stratum corneum was investigated. In the absence of iontophoresis, the rate of penetration was greatest at the higher pH values where lignocaine exists mainly in the unionized form; iontophoresis was most effective at the lower pH values where lignocaine is mainly ionized. At pH 3.4 and 5.2, the flux increased during iontophoresis, by approximately 8.5 and 4 times, respectively, relative to that occurring without iontophoresis. The present results suggest that some weak electrolytes which show poor percutaneous penetration may be administered topically using iontophoresis provided the drug is kept in a highly ionized form.

Drug-related admissions to an Australian hospital

This study was conducted to determine the prevalence of drug‐related hospital admissions in southern Tasmania, Australia. The causes of consecutive admissions to medical wards of the Royal Hobart Hospital were reviewed. Comprehensive data were collected over a 10‐week period on 691 admissions (median age: 67 years and range: 11–97 years; 50.8% males). Sixty‐eight (9‐8%) of the admissions were classified as being either probably or definitely drug‐related. Most of these admissions were attributable to intentional overdose (38.2%) or an adverse drug reaction (30.9%). The overdoses often involved benzodiazepines or antipsychotics. Gastrointestinal bleeding related to the use of nonsteroidal anti‐inflammatory drugs was the most common adverse drug reaction (38.1% of all reactions). Other drug‐related admission categories were poor compliance (14.7%), dosage decrease or therapy cessation by a doctor producing an exacerbation of symptoms (7.4%), substance abuse (4.4%) and drug interaction (4.4%). Patients with a drug‐related admission were, on average, younger than the other medical admissions, with no significant difference in gender. Patients admitted due to an overdose or substance abuse were younger than other drug‐related admissions and non‐drug related admissions. In conclusion, this study has determined that almost 10% of medical admissions to the hospital are drug‐related and it is estimated that 40 to 50 elderly people are admitted each year suffering from gastrointestinal bleeding related to nonsteroidal anti‐inflammatory drugs.

Percutaneous-Absorption of Steroids - Relative Contributions of Epidermal Penetration and Dermal Clearance

The permeation of triamcinolone, hydrocortisone, prednisolone, corticosterone, triamdnolone acetonide, testosterone, and betamethasone-17-valerate through excised human stratum corneum was quantified. The time course of permeation could be adequately described by a simple diffusion model suggesting that shunt transport may not be important. The disappearance of these steroids from aqueous solutions applied to human and rat dermis was also monitored. The concentrations of unbound steroid in the viable epidermis appeared to be mainly related to the blood perfusion rate in the dermis and, more importantly, to the lipophilicity of the steroid. The most lipophilic steroids penetrated the human epidermis at the fastest rates but are cleared from the viable epidermis at rates comparable to those found for more polar steroids.

Topical Absorption of Methotrexate - Role of Dermal Transport

Abstract The relative contribution of epidermal and dermal transport of methotrexate was examined in an attempt to define the concentration of methotrexate likely to be found in the viable epidermis. Dermal transport was examined using human dermis and an in vivo rat model. Epidermal transport was assessed using excised human stratum corneum. Methotrexate was rapidly absorbed into the dermis from aqueous solutions, its clearance being facilitated by both the dermal blood supply and diffusion into the dermis. The aqueous solution pH affected the rate of penetration of methotrexate through the stratum corneum. Maximal steady-state concentration in the viable epidermis estimated from the epidermal permeability coefficient and clearance were found to be lower than the concentrations reported as being required for the effective management of psoriasis.

Iontophoretic transport of weak electrolytes through the excised human stratum corneum.

The effect of iontophoresis on the rate of permeation of a number of therapeutically active weak acids and bases through excised human stratum corneum has been examined, over a range of pH values. It has been shown that the amount of ionized drug species present in the drug solution is an important factor in the delivery of acids and bases by this route and that the molecular weight of the drug does not influence the rate of delivery by iontophoresis.

The storage of selected substances in aqueous solution in polyethylene containers: The effect of some physicochemical factors on the disappearance kinetics of the substances

Abstract The disappearance kinetics of certain solutes in aqueous solution during storage in polyethylene containers is described. For solutes with low affinity for polyethylene, loss is characterized by mono-exponential kinetics. If the solute has a strong affinity for the polyethylene, bi-exponential kinetics exist due to significant uptake of solute into the polyethylene in addition to loss by permeation. A ‘compartmental’ model is used to examine the observed kinetics and is based on sorption of the solute by the container wall followed by permeation of the solute into the atmosphere. The disappearance kinetics of the solutes examined in this study is dependent on the formulation of the solution to be stored in the container, presoaking of the container in solutions of the solute, and the nature of the external environment in which the containers are stored.

Factors Affecting the Availability of Organic Nitrates From Plastic Infusion Systems - Structure of Organic Nitrate, Nature of Plastic and Effect of Temperature

Abstract The organic nitrate most recently introduced for clinical use (isosorbide-5-mono-nitrate) is not lost by sorption into the plastics of infusion systems. Other organic nitrates with 2 or 3 nitrate groups are lost by sorption into the plastic matrix of infusion systems at ambient temperature. At higher temperatures, evaporation of nitroglycerin and ethylene glycol dinitrate from the plastic to the atmosphere also contributes to the total loss of these compounds. The temperature-dependent sorption of all 3 organic nitrates by the plastic infusion bags is accounted for by changes in the diffusion coefficients of the organic nitrates in the plastic matrix, the plastic-water partition coefficients being independent of temperature. The extent of loss of the 3 organic nitrates corresponds to the rank order of their plastic (and organic solvent)-water partition coefficients i.e. nitroglycerin > isosorbide dinitrate > ethylene glycol dinitrate. It is suggested that the chloroform-water partition coefficient may be a useful parameter for the prediction of the interaction of a drug with polyvinyl chloride infusion systems.

FATE OF CHLORBUTOL DURING STORAGE IN POLYETHYLENE DROPPER CONTAINERS AND SIMULATED PATIENT USE

The disappearance of chlorbutol from aqueous solutions stored in polyethylene containers under various experimental and simulated patient use conditions is described. Chlorbutol is lost by sorption into the container wall, container insert and by permeation into the external environment. The extent of chlerbutol loss from solution and uptake by the container components is dependent on temperature, chlorbutol concentration and the closure used. Aqueous chlorbutol solutions stored in the polyethylene container evaluated have a predicted shelf‐life (time for 10% loss) of about 4 months at 25d̀C and 8 months at 20d̀C. Negligible loss is found during simulated patient use over 1 month.

The effect of each of three physicochemical variables on solute uptake by polyvinylchloride infusion bags

Abstract The effect of each of three physicochemical variables, solute concentration, electrolyte concentration and temperature on the uptake of six model solutes by Polyvinylchloride (PVC) infusion containers has been investigated. It has been shown that the solute uptake is independent of the initial concentration of the solute and that both temperature and electrolyte concentration have significant effects on the extent of solute loss. The Arrhenius equation has been used to described the temperature effect on solute uptake into PVC bags. The extent of solute uptake from solution in the presence of electrolytes without large ions is a function of increasing ionic strength. It is suggested that the sorption number which can be used to predict solute uptake needs to be adjusted by the use of correction factors for temperature and for vehicle ionic strength, as appropriate.

Uptake of Solutes by Plastic Infusion Tubing Mathematical Solutions

Abstract The uptake of solutes from aqueous solutions by plastic containers has received considerable attention in recent years. However, the loss of solute from aqueous solutions during flow through plastic tubing has not been as extensively investigated. In this work, the authors present four models to describe the sorption of solute during flow through tubing. These models represent the solution as either a well-stirred compartment or convection flow in a tube, and the plastic as either a well-stirred compartment or a matrix in which diffusion occurs in a radial direction. The time course of outflow solute concentrations observed experimentally after solute infusion into either Tygon or polyvinylchloride tubing was well described by the analytic solutions obtained. The diffusion models appeared to give the more satisfactory fit of the data. However, the data fit showed only small qualitative differences compared to the comportment models. A number of parameters are required to define each model limiting their usefulness. Accordingly, a number of simulations were undertaken to determine he relative effect of each parameter on the outflow concentration profile. As anticipated, the flow rate, the plastic water partition coefficient and the nature of the tubing were important. Extensive loss is most likely at low flow rates when a solute has a high affinity for the infusion tubing.