N. E. Richardson

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 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 °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.

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.

THE PREPARATION AND PROPERTIES OF POLYAMIDE MICROCAPSULES CONTAINING PILOCARPINE IN SOLUTION

As p a r t of an invest igat ion i n t o the po ten t i a l use of microcapsules f o r the delivery of drugs t o the eye, we have studied the preparation of polyamide microcapsules containing pilocarpine i n solution. I n i t i a l attempts t o prepare nylon 6:10 microcapsules by i n t e r f a c i a l polymerization i n rapidly s t i r r e d two phase systems using reported methods (Chang e t a 1 1966; Shiba e t a 1 1970) proved d i f f i c u l t , only s o l i d p a r t i c l e s of polymer being formed. After varying several f ac to r s involved i n the polymerization process, successful formation of spher ical microcapsules was achieved by including a cross-linking agent, polyethyleneimine, i n the aqueous phase. Harvesting of the capsules required centrifugation i n conjunction w i t h washings i n cyclohexane, acetone and f i n a l l y 5% Tween 20 solution. The capsules had a median volume diameter of about 20pm a s determined using a Coulter Counter and e lect ron scanning micrography showed them t o be hollow with a t h i n polymeric membrane.

COMPETITIVE SORPTION BEHAVIOUR IN NYLON 6

The study of drug-plastics interactions is of importance in the design and devel ment of pharmaceutical containers and polymeric controlled release devices. Generally, such interactions have been studied for single solute systems but in practice, solutions in contact with the plastic may be more complex containing more than one solute. We have investigated the interaction of four model compounds with Nylon 6 powder from single solute and binary solute solutions to assess passible competitive sorption effects. The model compounds selected (4-nitropheno1, phenol, 4-methoxybenzoic acid and benzocaine) possess functional groups common to many drugs. Previous reports have shown that the sorption of aromatic weak electrolytes by Nylons increases proportionately as the concentration of drug in the unionised form increases (Richardson and Meakin 1974). Sorption isotherms were therefore determined at a pH which optimised the concentration of unionised species present. The sorption of all four compounds gave rise to linear C 1 type sorption isotherms (Giles 1974) which may be characterised by their slopes (K values). At higher concentrations, the isotherm for 4-nitrophenol showed a plateau (C2 type isotherm) indicating that the solute is saturating the available sorption sites. No competitive sorption effects were observed from mixtures of 4-methoxybenzoic acid and benzocaine (table 1). The sorption of 4-nitrophenol by Nylon 6 powder, from phenol/4-nitrophenol mixtures, decreases as the amount of phenol present increases (figure 1). At higher concentrations of total phenols the isotherm for 4-nitrophenol changed from C 1 type to Z type (figure 1) with an associated plasticization of the polymer matrix which can be observed visually. sorption of phenol is unaffected by the presence of 4-nitrophenol until at higher concentrations the system again becomes plasticised, suggesting that phenol has a higher affinity for the polymer matrix. This difference in sorption behaviour may be due to the phenolic compounds forming strong hydrogen bonds with amide groups in the polymer whereas the non-phenolic compounds may interact by nonspecific Van der Wads forces. Thermodynamic parameters calculated from K values determined over the range 7O 60° also support the concept of a dual binding mechanism. 0.47 and + 16.98 K.J mo1-l respectively and dG interaction (323 K) values were O P