B. J. Meakin

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°, 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.

The antimicrobial efficiencies of contact lens solutions

The antimicrobial efficiencies of 34 commercially available contact lens solutions has been tested against Pseudomonas aeruginosa, Staphylococcus aureus, Micrococcus luteus and Candida albicans. A standard inoculum of 106 organisms ml−1 was placed in a sample of a contact lens solution and samples taken at various times up to 48 h. These were placed in a recovery medium and the presence or absence of growth noted after 48 h incubation at 37°. Of 14 solutions used to soak and disinfect lenses only 4 inactivated all four test strains within 1 h, 7 within 4 h, while 6 solutions allowed growth of one or more test organisms even after 24 h contact. Of the remaining 20 solutions, with their various functions such as cleaning and wetting of lenses, 13 failed to inhibit one or more test strains after 24 h contact. Some form of control of the manufacture and presentation together with minimum standards of antimicrobial efficiency would seem to be desirable.

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 is 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.

The sorption of benzocaine from aqueous solution by nylon 6 powder

The sorption of benzocaine by nylon 6 powder from aqueous solution has been examined under varying environmental conditions. The extent of sorption increases with increase in electrolyte concentration, and with pH up to about pH 4. Increasing temperature reduces the amount of drug sorbed. In all cases, the sorption isotherms were linear over the concentration ranges studied, and can be described by a simple distribution law which allows the effects of ionic strength and pH to be predicted. The interaction is believed to involve hydrogen bond formation between benzocaine and the amide groups of the nylon after penetration of the polymer matrix by the drug.

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.

An observation on the determination of thiomersol at preservative concentration by flameless atomic absorption spectroscopy.

Bsclofen has been shown to induce an increase in Cli du~ in crayfish muscle, competition studies with G ~ ~ A suggesting an action on the same receptor @sen et al 1978). Similarly, recent electrophysiological s&ies have shown baclofen to produce GABA-like, bicucdline sensitive effects (Fox et a1 1978). Our own khavioural studies have indicated that baclofen may be a partial agonist or dualist at the GABA receptor, and that these effects are weakly sensitive to antagonism by ,+Hotoxin (Waddington & Cross 1979). These studies suggest that baclofen can weakly interact directly with GABA receptors and that this effect occurs at concentrations considerably below those active on GABA release mechanisms. However, the GABAergic activity of baclofen is substantially less than that of potent and specific GABA agonisls such as muscimol. It should not be overlooked that the most potent action of baclofen may be to inhibit release of excitatory amino acid neurotransmitters (Potashner 1978; Fox et al 1978), in a manner stereospecific for the (-)-isomer (Ault & Evans 1978). At much higher concentrations of baclofen, GABA receptors may be stimulated directly and this effect does not show stereospecificity (Cross & Waddington 1978). In discussing the therapeutic potential of baclofen, particularly in schizophrenia, Kerwin & Pycock (1978) have failed to note both that reduced activity of the GABA-synthesizing enzyme glutamic acid decarboxylase in postmortem brain tissue from schizophrenic patients is not a replicable finding (McGeer & McGeer 1977; Crow et al 1978) and that placebo-controlled trials of baclofen in schizophrenia have clearly indicated SH-GABA binding with an IC50 of 80 p ~ . its lack of antipsychotic effect (Gulmann et a1 1976; Bigelow et al 1977). In the light of its duplicity of action and low potency, baclofen would seem to be a poor pharmacological tool for the study of GABAergic mechanisms in experimental animals and in the clinic. May 9, 1979

THE STABILITY OF SALBUTAMOL SOLUTION

Only one study into the stability of SalbutamOl has been previously reported (Wall and Sunderland,l976), This work was Of limited scope and utilised fluorimetric and colorimetric assay techniques, b u t neither of these was proven to be stability indicating. We have therefore initiated a more complete study into the stability profile of salbutamol and developed a reversed phase, ion paired HPLC assay method. The technique involves a preliminary separation of non-basic degradation products by passage through an SP-Sephadex C 2 5 cation exchange column. The d r u g and basic degradation products are then eluted with dilute ammonia and lop1 aliquots of the eluant injected Onto a 1Ocm Spherisorb 55 ODS column, using a mobile phase consisting of 0.06%perchloric acid and 0.004% sodium dodecyl sulphate in 20% acetonitrile. 1-(4i1ydrOxy-3-methylphenyl) -Z-(t-butylamino) ethanol is used as internal standard and detection is at 278nm; quantification involves peak area ratios obtained via a Pye-Unicam DP88 Minigrator. Thin layer chromatograms of degraded drug solutions exhibit up to 6 additional spots and it has been verified that none of these breakdown products appear under the salbutamol peak on the HPLC trace.

The effect of drug concentration on the thermal (dark) degradation of promethazine 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° can be fitted to first order rate plots at drug concentrations up to 1·56 × 10−2m (0·5%) and to zero order rate plots at drug concentrations greater than 9·35 × 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 data have been interpreted on the basis of a first order monomer process and a half order micellar process occurring simultaneously.

The effect of heat, pH and some buffer materials on the hydrolytic degradation of sulphacetamide in aqueous solution

The hydrolytic degradation of sulphacetamide has been investigated under anoxic conditions over a wide range of pH values and at different temperatures. The sole breakdown product is sulphanilamide. The reaction is essentially independent of pH (measured at 25°) over the range 5 to 11, but is subject to catalysis by buffer constituents. Below pH 4 specific hydrogen ion catalysis occurs. Calculation of activation parameters leads to the conclusion that sulphacetamide solutions can be satisfactorily autoclaved provided they are not subsequently refrigerated.

The influence of cosolvents and substrate substituents on the sorption of benzoic acid derivatives by polyamides

The sorption of some substituted benzoic acid derivatives by polyamides (nylons) from aqueous solution has been examined and the influence of their nature together with those of the cosolvent and polymer have been assessed. In all cases the sorption isotherms were linear and could be expressed by a simple distribution law, enabling the influence of cosolvent concentration to be predicted. The sorption of a series of p‐substituted benzoic acids and some of their esters is related to their solubility except where the p‐substituent is capable of hydrogen‐bonding with the polymer. The extent of the interaction is also dependent upon the amide frequency of the polymer.