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Biomedical subjects

B J Meakin

Publications and source records attributed to B J Meakin.

At least 19 recordsLinked to original sources
PubMed2005

Modulite: a simple solution to a difficult problem.

The development of HFA-based pMDIs has proved difficult due to differences in the physico-chemical properties of CFC and HFA propellants. However, the development of solution formulations instead of suspensions has provided a way to formulate products whose cloud characteristics can be modulated in a controlled manner by permitting different formulation and device hardware variables. The new approach has proved successful in formulating several different drugs including steroids and has now been applied to developing a formoterol Modulite solution formulation characterized by good chemical stability, delivery performance, and clinical results.

Aerosol Propellants↗
PubMed1998

The effect of flow rate on drug delivery from the Pulvinal, a high-resistance dry powder inhaler.

Dry powder inhalers vary widely in their resistance to flow. When the resistance is high, airway resistance can be neglected and inspiration rates will be determined primarily by the device. Provided that the patient can generate adequate flow rates to aerosolize the dose, variability of emitted dose and fine particle dose should be reduced. For in vitro simulation, these concepts are explored using a Pulvinal device. In conditions likely to be encountered in patient use, the emitted dose showed little dependence (80-102 micrograms) as the flow rate increased from 28 to 63 L/min. The fine particle dose was more sensitive, increasing by a factor of 1.6 from 22 to 35 micrograms. These variations are less than those observed with the Turbohaler, a device of intermediate resistance and very much lower than those observed with the Rotahaler, a low-resistance device.

Bronchodilator Agents↗
PubMed1981

The mechanism of interaction between chlorhexidine digluconate and poly(2-hydroxyethyl methacrylate).

The extent of the interaction between chlorhexidine digluconate and poly(2-hydroxyethyl methacrylate), (PHEMA), is independent of temperature between 22-50 degrees C which is consistent with an ion-ion interaction mechanism. Different contact lens materials exhibit different affinities for chlorhexidine digluconate, the extent of uptake correlating in rank order with the number of free carboxylic acid sites in the polymers. Esterification of the carboxyl groups with diazomethane, resulted in a reduction in the affinity of the treated polymers for chlorhexidine to a near basal level. The uptake of chlorhexidine in soaking solution experiments involving lenses made from PHEMA and the more ionic material, poly(2-hydroxyethyl methacrylate-co-isobutyl methacrylate-co-methacrylic acid), was consistent with their carboxylate content. However, the fraction of bound disinfectant released was lower from the terpolymer, suggesting there are differences in bonding strengths between chlorhexidine and different contact lens hydrogels.

Adsorption↗
PubMed1980

The use of polyamide coatings for selective adsorption control on activated charcoal.

Polymer-coated, activated charcoal granules have found considerable use for the direct detoxification of blood in cases of uraemia and drug overdose. Although polymer coating materials are presently selected for their biocompatibility, more selective polymers could be used to increase the adsorption capacity for specific drugs and toxins. To gain an understanding of the fundamental factors influencing these adsorbent systems, we have investigated a possible selective coating material, nylon 6 and studied its influence on adsorption rates of simple model compounds when applied as a thin coat to activated charcoal granules. Thermodynamic studies have shown that phenolic compounds interact with the polymer by a hydrogen bonding mechanism, whereas nonphenolic compounds probably bind less strongly due to Van der Waals type interactions. Kinetic studies have shown that the selectivity of charcoal granules for phenolic compounds was increased by coating the granules with a thin layer of nylon 6. The increase in selectivity is probably a result of the different binding mechanism between solute and the polymer. These studies have shown that possible selective coatings may be evaluated more effectively on the basis of simple preliminary drug-plastics interaction studies.

Adsorption↗
PubMed1980

The influence of various counter ions on the interaction of chlorhexidine with the hydrophilic contact lens polymer, poly(2-hydroxyethyl methacrylate).

The commercially available salts of chlorhexidine were found to interact with the hydrogel poly (2-hydroxyethyl methacrylate) to different extents, the affinity for the polymer decreasing in the order acetate, gluconate, chloride. The uptakes of the acetate and gluconate salts were almost entirely irreversible over the concentration range studied. The influence of some alternative counter ions, namely amino acids and dicarboxylic acid salts, was examined and found to generate a three-fold variation in the extent of the chlorhexidine interaction. Uptakes were greatest for counter ions that were either hydrophobic in character or bore a net negative charge. Only two compounds, glycine and monosodium oxalate, were successful in reducing the extent of sorption below that observed for chlorhexidine hydrochloride.

Acetates↗
PubMed1980

On the anomalous sorption behaviour of chlorhexidine with poly(2-hydroxyethyl methacrylate).

General observations of solute: plastic interactions would suggest that the sorption of the cationic preservative, chlorhexidine, with poly (2-hydroxyethyl methacrylate) (PHEMA) is not only unexpected but also atypical in its properties. The polymer and preservative were investigated independently and the sorption of PHEMA with simple solutes, namely benzoic acid, benzocaine and aniline found to exhibit conventional properties. The single exception was the uptake of small amounts of benzocaine and aniline cations at acidic pH's. In order to elucidate the sorption characteristics of chlorhexidine a series of N1-(p-chlorophenyl)-N5-alkylbiguanide acetates were synthesized. The anomalous sorption behaviour observed between PHEMA and the bis biguanide, chlorhexidine, was also found to be characteristic of these monofunctional biguanide derivatives. The extent of the interactions increased with increasing alkyl chain length (R = methyl to n-octyl), this being interpreted in terms of an interaction binding mechanism via the biguanide functional group stabilized by van der Waal's forces between the alkyl chain and the polymer backbone. Atypical sorption behaviour was observed for simple organic cations, biguanide and N2-phenylbiguanide acetate with PHEMA, a possible inference being that this is a general characteristic of all cationic sorption with PHEMA.

Adsorption↗
PubMed1978

The effect of drug concentration on the thermal (dark) degradation of promethazin hydrochloride in aqueous solution.

The thermal (dark) degradation of promethazine hydrochloride in aqueous solution presents a complex kinetic picture. The process is oxygen dependent and is modified by EDTA. In citrate buffer, pH 4.0, ionic strength 0.5M, containing 0.1% EDTA, the thermal degradation at 90 degrees can be fitted to first order rate plots at drug concentrations up to 1.56 x 10.27 (0.5%) and to zero order rate plots at drug concentrations greater than 9.35 x 10.2M (3.0%). At intermediate concentrations no simple equation can describe the data. These effects have been correlated with the formation of drug micelles and the rate date have been interpreted on the basis of a first order monomer process and a half order micellar process occurring simultaneously.

Chromatography, Gas↗
PubMed1978

The interaction of preservatives with polyhydroxyethylmethacrylate (polyHEMA).

The interaction of the four most commonly used preservatives in contact lens solutions (chlorbutol, thiomersal, chlorhexidine gluconate and benzalkonium chloride) with polyhydroxyethylmethacrylate (polyHEMA), has been examined. Benzalkonium chloride and chlorhexidine gluconate show typical high affinity type isotherms. The interaction of benzalkonium chloride with polyHEMA from aqueous solution was reversible whereas that of chlorhexidine was only reversible in the presence of electrolyte or surfactant. Chlorbutol showed a typical reversible linear isotherm. Thiomersal does not interact with polyHEMA above pH 5.0. The extent of chlorhexidine--polyHEMA interactions in increased by the presence of formulatory adjuvants such as electrolyte and hydrophilic polymers. PolyHEMA lenses that apparently have been equilibrated with chlorhexidine gluconate will, on the addition of fresh preservative solution, bind further quantities of chlorhexidine above that which would be predicted from the sorption isotherm.

Acrylic Resins↗
PubMed1977

The influence of temperature on the sorption of benzocaine by nylon 6 from aqueous cosolvents.

The influence of temperature on the sorption of benzocaine by nylon 6 powder from aqueous cosolvents has been assessed. At about 30 degrees discontinuities appear in the Van't Hoff plots for sorption from water and aqueous PEG 400, which may be attributed to transitional changes in the polymer structure. No such discontinuities are apparent for sorption from aqueous ethanol over the temperature range 15-60 degrees, which is indicative of plasticizaton by this cosolvent.

Adsorption↗
PubMed1977

Loss of antibacterial preservatives from contact lens solutions during storage.

The preservative content of 34 commercially available contact lens solutions has been determined. Over half of the solutions contained less than 90% of the stated preservative content. Storage tests conducted at 40 degrees, using both simulated and commercially available contact lens solutions in plastics containers of the type used to present these products showed that thiomersal and chlorbutol appeared to be sorbed by these containers in contrast to benzalkonium chloride and chlorhexidine gluconate which interacted mainly by a surface adsorption process. The extent of any interactions was dependent upon the type of plastics material used to fabricate the container.

Anti-Infective Agents, Local↗