Lens Care Products

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Lens Care Products

Masood ChowhanRalph StoneAlcon Laboratories, Fort Worth, Texas, U.S.A.

INTRODUCTION

Contact lenses are made of polymeric materialsdesigned and fabricated to correct vision. Becausethese lenses are removed from the eye after a pre-scribed wear time, lens care products are required toclean, disinfect and rinse them prior to reinsertion toavoid ocular infections and other complications. Lenscare products are also required to enhance the comfort

of lens wear.

HISTORICAL OVERVIEW

Lens care products are relatively new compared tomany other pharmaceutical products. Leonardo daVinci was the first to conceive the concept of the con-tact lens. In 1508 he illustrated the concept of visioninvolving upside down images with a water-filledsphere covering the eye. However, the actual develop-ment of contact lenses did not occur until about 100

years ago (18871888) when scleral contact lenses werefabricated. The three innovators credited for this areDr. A.E. Fick, a physician in Zurich, F.A. Mueller, amaker of prosthetic eyes in Germany, and Dr. EugeneKalt, a French physician. The earlier lenses were madeof glass. In the late 1930s (19371939), Mullen, Obrigand Gyorrfy are credited with fabricating plastic con-tact lenses made from methyl methacrylate (PMMA).However, Kevin Tuohy, who filed a patent for contactlens design in 1948, is recognized as the father ofmodern day corneal contact lenses. These early lenseswere rigid and uncomfortable with very low oxygentransmission. Advances in rigid lens technology have

provided materials capable of oxygen transmissionrequired to maintain corneal health. In the 1960s OttoVicterle developed the hydrophilic soft contact lensfrom polyhydroxyethyl methacrylate (HEMA).Hydrophilic soft contact lenses are the primary lensesavailable today. Since then, significant technologicaladvances have been made in contact lens material,designs, and manufacturing processes. In 1990, theestimate of contact lens wearers in the United Statesalone was around 30 million.

The commercialization of the first pharmaceuticalquality lens care products occurred in the 1950s. HarryHind, a pharmacist and founder of the Barnes-HindCompany, has been credited as one of the first todevelop and commercialize a wetting and storage solu-tion for the rigid PMMA plastic lenses. Prior to hisefforts, the literature mentions formulation of a salinesolution containing sodium bicarbonate to be usedwith scleral lenses made from glass.

CURRENT CONTACT LENS MATERIALS

AND FUTURE DIRECTIONS

Most of the materials currently used in fabricatingcontact lenses have been available since the mid-1960s with the exception of polymethyl methacrylate.Lens materials can be broadly classified as follows:

Rigid Gas-Permeable Lenses:

Cellulose acetate butyrate Silicone Silicone acrylate Fluoro silicone acrylate t-Butylstyrene t-Butylstyrene-co-silicone acrylate

Soft Hydrophilic Lenses:

Polyhydroxyethyl methacrylate Polyhdroxyethyl methacrylate-co-methacrylic acid Polyglyceryl methacrylate Polyhydroxyethyl methacrylate-co-polyvinylpyrro-

lidone Polyvinylpyrrolidone-co-methyl methacrylate Polyhydroxyethyl methacrylate-co-silicone (silicone

hydrogel)

In addition to these materials, several others, suchas polyurethanes, polysulfones, polyvinyl alcohol,and various copolymers, have been tried or are underdevelopment. Recently, silicon hydrogel lenses withhigh oxygen permeability were marketed. The future

Encyclopedia of Pharmaceutical Technology DOI: 10.1081/E-EPT-100001917Copyright # 2007 by Informa Healthcare USA, Inc. All rights reserved.2202


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trends in material development will continue to includepolymers which have a high degree of oxygen per-meability, resist accumulation of metabolic productsof the cornea, and materials that resist lens depositsand bacterial attachment on lens surfaces to minimizethe potential for ocular infection.

Classification of Contact Lenses

Currently Marketed

During a period beginning from mid-1970, numeroushydrophilic and rigid gas-permeable lenses were intro-duced into the market. Although many had similarbasic chemical compositions, they contained differentadditives designed to achieve desirable properties orto avoid infringement of existing patents. Such a pro-liferation of contact lens materials created confusionregarding Food and Drug Administration (FDA) cri-teria for approval of contact lenses and their care pro-

ducts. In the mid-1980s, the FDA worked with thecontact lens manufacturers and evolved a classificationfor soft contact lenses based on the ionic or non-ionicnature of polymers constituting the lens material andthe water content. A classification was also workedout for rigid gas-permeable (RGP) lenses based onthe chemical nature of the polymers. It is interestingto note that contact lenses and their care products wereoriginally considered as drugs. However, upon passageof the U.S. Medical Device Act in 1996, contact lenseswere reclassified as devices. Contact lenses and theircare products were considered Class-III devices,which mandate the filing of a premarket approval

application and obtaining FDA approval prior to mar-keting. Recently these products were reclassified asClass II devices and are currently cleared for marketingunder the 510(k) premarket notification section of theregulations.

LENS CARE PRODUCTS BY FUNCTIONAL

PURPOSE

Marketed lens care products fall mainly into the fol-lowing categories: cleaners, disinfectants, lubricants,

and multipurpose products. Cleaners are subdividedinto daily or weekly cleaners. Disinfectants comprisesolutions containing chemical antimicrobial agents,which do not require heating the lenses, and preservedor unpreserved saline solutions, which are used with anelectrical thermal device for lens disinfection. Theseproducts are also used to rinse contact lenses. Lenslubricants are intended to enhance the comfort of lenswear and are used prior to insertion and during wear.Multipurpose solutions are intended to accomplish

two or more of the functions described earlier (cleaning,rinsing, and disinfection).

Rigid lens care also includes conditioning solutionsto make the basic hydrophobic polymers wettable whenplaced on the eye.

PRODUCTS FOR CLEANINGSOFT CONTACT LENSES

Lens Deposits

Composition

Basically there are two types of deposits: those result-ing from tear components and those derived fromother sources. Tear components especially proteinscan accumulate on the lens surface. These proteinscan denature or change conformations during absorp-

tions on over tissue. Most deposits, with the exceptionof those that are tenaciously bound to the lens, can becleaned easily with a surfactant-type of daily cleaner.Deposits resulting from tear components includeproteinaceous deposits such as lysozyme, lactoferrin,albumin, globulins, etc. Proteinaceous deposits arepresent on all types of lenses. However, the amountsdiffer, depending on the number of ionic charges onand in the lens, the pore size, and the relative hydro-phobicity of the polymers. For example, conventionalnon-porous and uncharged hard PMMA lenseswith a hydrophobic surface attract very little protein-aceous deposits. Among the soft contact lenses with

hydrophilic surfaces, the extent of deposits differsamong various groups. For example, Group-4 lenses,which exhibit considerable negative charges due tomethacrylic acid content, interact readily and heavilywith a positively charged protein (lysozyme). Group-2hydrogel lenses have no ionic charges, but can acquiresubstantial amounts of protein because of their largepore size. Besides protein deposits, lipid depositsare also found on contact lenses. These deposits aremore common with rigid gas-permeable lenses becauseof their lipophilic nature. Such deposits may includecholesterol esters, wax esters, triglycerides, sterols,fatty acids, etc. Calcium present in tears results in

calcium carbonate or phosphate-type of deposits aswell as so-called mixed deposits (calcium bondedto organic compounds). Such deposits are commonmainly in high water content soft contact lensesand are difficult to remove without damaging thecontact lenses. Other deposits result from the patientenvironment. These include deposits resulting fromcosmetics, make-up, and hair-spray, as well as materi-als from the wearing environment such as pollen dustand debris.

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Problems associated with lens deposits

Cleaning is one of the most important steps in contactlens care. It helps in the removal of surface debris andcontaminating microorganisms, thus facilitating thedisinfection process. Improperly cleaned lenses cancause discomfort, red eye, decrease in visual acuity,and giant papillary conjunctivitis (GPC). The last oftenrequires discontinuance of lens wear, at least until thesymptoms clear. The change from heat to cold disinfec-tion technology and the introduction of disposablelenses may have reduced the incidence of GPC. How-ever, since these lenses can be worn on an extendedbasis for up to seven days without cleaning, GPC canstill occur, as has been noted in the literature.

Classification of Lens Cleaners

Daily cleaners vs. weekly cleaners

Daily cleaners generally contain surfactants and areused every day. They may also contain abrasive(deposit-shearing) particles, which enhance productperformance. Commonly used daily cleaners withdeposit shearing particles are listed in Table 1.

There are two types of weekly cleaners: those con-taining enzymes and those containing concentratedsurfactants. Products containing enzymes for dailyuse are usually accepted by the patients and recom-mended by practitioners. Commonly used enzymaticproducts are listed in Table 2.

In-the-eye vs. out-of-the-eye cleaners

Most of the cleaners marketed are out-of-the-eye clea-ners; however, in recent years there has been a trend totry to develop cleaners for use while the lenses areinserted. A specific instance where such products couldbe beneficial is the case of the extended-wear lenses,which are not removed daily but are worn up to a weekat a time. Generally, these cleaners are less effective inremoving deposits already formed on the lens surface.However, they may play a role in retarding depositformation.

Consumer vs. professional use cleaners

Cleaners for lens wearers are used either on a daily orweekly basis and are fairly innocuous. Even upon grossmisuse, they are not likely to be sight-threatening.Professional cleaners, however, are potent as well astoxic if not used properly. They are also more likelyto damage the lens if used too frequently.

Active Components of Lens Cleaners

Surfactants

Surfactants are broadly classified into non-ionic, anio-nic, cationic, and amphoteric types. Non-ionic andamphoteric surfactants are most commonly used incontact lens cleaners, because strong anionic surfac-tants are generally toxic to the cornea. The recom-mended procedure by the manufacturer removesseveral types of deposits, except the most tenaciouslybound and denatured proteins, lipids, and mucins.Surfactant-type cleaners are also effective in removinggreater than 99.9% of microorganisms contaminatingthe lens. There are several mechanisms for their effec-tiveness, which include displacement of contaminantsfrom the surface by mechanical force after the surfacedebris has been loosened as a result of a reduction inthe interfacial tension. In addition, surfactants act byemulsification and micellar solubilization. They mayalso play a role in preventing or retarding depositionof contaminants.

Enzymes

Enzymes are biochemical molecules responsible forcatalyzing reactions in which certain chemical bondsare broken. Their mechanism of action in cleaninginvolves attacking substrate protein, lipid, and mucindeposits, and fragmenting them into smaller moleculeswhich are readily removed by the mechanical action ofrubbing with the fingers and rinsing. Marketed pro-ducts contain different enzymes, such as papain, pan-creatin, and subtilisin. Papain and subtilisin are onlyproteolytic in nature, whereas pancreatin is a broad-spectrum enzyme containing protease, lipase, and

Table 1 Daily cleaners with shearing particles

Trade name Manufacturers Type of particle Used with

OPTI-CLEAN Alcon Nylon Soft, PMMA, RGP

OPTI-CLEAN II Alcon Nylon Soft, PMMA, RGP

OPTI-FREE daily cleaner Alcon Nylon Soft, PMMA, RGP

Boston cleaner Polymer technology Silica PMMA, RGP

Boston advance cleaner Polymer technology Silica PMMA, RGP

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amylase enzymes that digest proteins, lipids, andmucins. Enzyme cleaners are effective in attacking alllens proteins, including the removal of tenaciouslybound and denatured deposits, that cannot be removedby surfactant cleaners. Traditional enzymatic cleaningof contact lenses is recommended usually once a week.The soaking time varies from 15 min to overnight, fol-lowed by a disinfection process. However, morerecently products have been introduced that can beused simultaneously during disinfection on a daily pro-cess. Certain enzyme products are recommended forthis single-step cleaning and disinfection, using a heator chemical regimen that enhances convenience andincreases user compliance.

Oxidizing agents

Oxidizing agents such as sodium perborate and sodium

percarbonate have also been used in cleaning contactlenses. None of these products are currently marketedfor that purpose in the United States. Products mar-keted earlier were withdrawn because of their deleteri-ous effects on lens polymers.

Deposit-shearing particles

Deposit-shearing particles are incorporated in suspen-sion form in some daily cleaners. These formulationsare more effective than daily surfactant cleaners asthey are capable of removing tenaciously bound anddenatured deposits. Some of the marketed products

contain polymeric beads or silica. When used as recom-mended, these products are very effective and do notscratch the lens surface.

Chelating agents

Chelating agents such as disodium edetate (EDTA) arecommonly used in lens care products to enhance theantimicrobial activity of preservatives and remove cal-cium and magnesium from the lens. EDTA is the most

effective chelating agent known for calcium and mag-nesium. Other chelating agents have been used suchas phosphonates, which are most effective against iron.

Solvents

Solvents such as isopropyl alcohol have been incorpor-ated in daily cleaners to aid in removing lipid type ofdeposits. Such solvents have been reported to affectcertain lens materials, especially silicone acrylate rigidgas-permeable lenses.

Accessory Cleaning Products

Hand soaps

In the daily care of contact lenses, wearers are

instructed to clean their hands with soap and to dryhands their hands with lint-free towels prior to hand-ling their lenses. Selection of the specific soap productis important. In addition, to cleaning the hands thor-oughly, it should be rinsing and should not cause ocu-lar irritation even if residual amounts are transferred tothe lens. With these considerations in mind, some handsoaps have, therefore, been designed specifically forcontact lens users.

Cleaning devices

The general method of daily lens cleaning involves rub-

bing lenses between the index finger and thumb orplacing the lens in the palm of the hand and rubbingwith the index finger after applying cleaning solutionto the surface. However, there are also special devicesavailable in the market for cleaning lenses. They aresaid to clean lenses more effectively and avoid poten-tial scratching by the fingers. These devices involvemechanical agitation and are manually or electricallyoperated. Ultrasound devices have been used mainlyby lens practitioners in their office. None of those

Table 2 Enzymatic products for contact lenses

Trade name Manufacturers Enzyme Source Dosage form

OPTI-FREE enzymatic cleaner Alcon Pancreatin Mammals Tablet

OPTI-ZYME enzymatic cleaner Alcon Pancreatin Mammals Tablet

SupraClens daily protein remover Alcon Pancreatin Mammals Liquid

Allergan enzymatic contact lens cleaner Allergan Papain Plant Tablet

ProFree/GP weekly enzymatic cleaner Allergan Papain Plant TabletUltrazyme enzymatic cleaner Allergan Subtilisin-A Microrganisms Tablet

ReNu effervescent enzymatic cleaner Bausch & Lomb Subtilisin Microrganisms Tablet

ReNu thermal enzymatic cleaner Bausch & Lomb Subtilisin Microgranisms Tablet

Sensitive eyes enzymatic cleaner Bausch & Lomb Subtilisin Microrganisms Tablet



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devices per se are effective in removing tenaciouslybound, denatured deposits.

PRODUCTS FOR DISINFECTING

CONTACT LENSES

Disinfection of contact lenses is an important step inpreventing ocular irritation, red eye, and potential lossof eyesight due to corneal ulcers resulting especiallyfrom Pseudomonas aeruginosa infections. The poreopenings of hydrophilic soft contact lenses are esti-mated to be between 3.0 and 7.0 nm, and are consider-ably smaller than the average bacterial particle size of0.21.0mm or fungus particle size of 26 mm. Evenviruses ranging in particle size from 25 to 200nm arelarge in size compared to the pore openings of softlenses. None of the microorganisms can penetrate anintact lens matrix. However, when lenses are not prop-erly cared for, some fungus growth facilitates the

penetration of fungal hyphae into the matrix.Contact lenses and their cases are frequently

contaminated by microbes. Although studies haveindicated that as many at 30% of lens cases are con-taminated, the incidence of permanent ocular damagedue to this is very low. Nevertheless, it is critical toproperly instruct lens wearers and emphasize theimportance of disinfection in order to avoid the poten-tial risk of ocular infection or damage to the eyesight.

Thermal vs. Chemical Disinfection

Both thermal and chemical methods are commonlyused for the disinfection of soft contact lenses. Withthe former, a case containing the lenses immersed insaline solution is heated by an electrical unit with apredesigned heating cycle. The current FDA require-ment for thermal disinfection by saline solutionrequires a minimum temperature of 80C for 10minwithin the contact lens case. This ensures eliminationof vegetative forms of ocular pathogens but not thespores.

The chemical method involves antimicrobial com-pounds with an adequate antimicrobial spectrum andbiocidal action. The FDA guidelines include the meth-

ods for determination of efficacy for all disinfectingsolutions. The initial testing process is defined as theelimination or reduction of microorganisms achievedover the disinfection period. The FDA guidelines alsoprovide a method for manufacturers to conduct usetests on purposely contaminated contact lenses, follow-ing a complete disinfection regimen, which includescleaning and rinsing. This test is generally known asthe FDA regimen test. The FDA guidelines specifythe types and levels of organisms as well as the details

of the test. Other methods using ultraviolet light,microwave, and ultrasonics, have been tried for lensdisinfection but are not widely applied because ofineffectiveness or deleterious effects on lens materials.

The advantage of the thermal method is that itensures complete elimination of vegetative forms ofmicroorganisms, whereas chemical disinfectants mayencounter some resistant organisms. Although thethermal method is preferable from the microbiologicalviewpoint, it has several disadvantages: It is a complexmethod involving the use of electrical devices. The fail-ure of an electrical heating unit to perform properlypresents a potential risk of ocular infection. Malfunc-tioning units and improper use may result in electricalshock to users and fires have been reported. If thesaline solution in the lens container evaporates duringthe heating cycle as a result of carelessness in not prop-erly tightening the lens case cap, the lens might bedamaged. Thermal disinfection has been cited in short-ening lens life and enhancing the formation of deposits

on the surface. This occurs especially if the lens has notbeen properly cleaned prior to thermal disinfection.The method is not practical for campers who arefrequently without an electrical outlet.

Chemical disinfection, on the other hand, is not aseffective in killing organisms as thermal disinfection,but has several advantages: It is simple to use, therebyensuring greater user compliance. Lens life is longerwith chemical disinfection as lenses are not subjectedto daily heat treatment. The method results in fewerdeposit problems as surface debris left on the lenssurface due to improper cleaning is not baked by heat.

The choice between thermal and chemical disinfec-

tion depends, to a large extent, on the recommendationof the lens practitioners. Factors involved include thewearers sensitivity to preservatives, needs, personalhygiene habits, and product cost. Today fewer heatdisinfection units are available.

Thermal Disinfection

Soft contact lenses were introduced in the UnitedStates in 1972. At that time, the thermal disinfectionmethod was the only method available. It uses eitherpreserved or unpreserved saline solution.

Unpreserved vs. preserved saline solutions

Prior to the commercial availability of pharmaceuti-cally prepared saline solutions, they were prepared bythe lenswearer using salt tablets and distilled water.This method was undesirable and created many pro-blems as the pH and osmolarity of such solutions werenot controlled, which often resulted in parameterchanges in some soft lenses. The major problem



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stemmed from non-compliance. In order to reducecost, tap water was often used instead of distilled waterfor preparing saline solutions, which resulted in min-eral deposits on the lens surface. Microorganismsproliferated in non-sterile saline solution preparedwith distilled water stored for a number of days andinstilled in eyes directly to hydrate contact lenses whilethey were worn. Such gross misuses resulted in ocularinfection affecting vision. By the mid-1980s productslabel and package inserts warned against the use oftap water for contact lens care. In the mid-1970s,pharmaceutically prepared sterile saline solution pre-served with thimerosal was introduced to eliminatethe disadvantages of home-made saline. However,thimerosal often caused a brownish and grayishlens discoloration and also led to red-eye and sensitiza-tion reactions in some patients. Soon after the intro-duction of pharmaceutically prepared preservedsaline solutions, most salt tablets were withdrawn fromthe market. They were, however, reintroduced because

of the red-eye and sensitization problems associatedwith thimerosal-preserved salines. In 1987, the FDAasked companies marketing salt tables for their volun-tary withdrawal because of several incidences ofkeratitis caused by Acanthamoeba species, resultingin significant loss of vision or eyesight of several lenswearers. Most of these cases were associated withthe use of salt tablets to prepare home-made salinesolution.

In the United States today saline solutions are mar-keted in preserved and unpreserved forms; both aresterile and pharmaceutically prepared. The unpre-served solutions are available in unit dose or multidose

plastic containers and multidose aerosols. In the latterinstance, the pressurized container and the construc-tion of the valve prevents innoculation of micro-organisms into the container during its use, thusmaintaining sterility more effectively in comparisonto multidose non-preserved saline solution inplasticcontainers. Non-preserved saline solution in anaerosol container is, therefore, preferred over non-preserved saline solution because it eliminates thepotential of irritation and sensitization reactionscaused by thimerosal and sorbic acid preserved salines.Such reactions may result in considerable patientdiscomfort and require temporary discontinuance of

lens wear. However, the newer preservatives Polyquadand Dymed do not cause significant levels of suchreactions. The disadvantage of unpreserved saline sol-ution in unit dose is higher cost. There is also a poten-tial risk of ocular infection as it is a common practiceamong lens wearers to leave their lenses in a lens casecontaining an unpreserved saline for several weeks,often without appropriate disinfection. Unpreservedsaline does not protect against proliferation of micro-organisms.

In contrast, preserved saline helps to preventmicrobial growth when lenses are not worn and storedin lens cases. They are also less costly in comparison tounit dose or multidose pressurized non-preserved sal-ine solution containers. As already noted, the principaldisadvantage of preserved saline solution is that someof the preservatives, such as thimerosal and sorbic acid,have the potential of causing irritation and sensitiza-tion in some patients. However, these reactions arenot sight-threatening. In most instances these symp-toms clear on discontinuance of the product withoutrequiring any drug therapy. Again, this problem nowappears to have been eliminated or greatly minimizedwith the introduction of newer preservatives such asPolyquad and Dymed.

Both preserved and unpreserved saline solutions aremultifunctional solutions. In addition to thermal disin-fection, they are also used to dissolve enzyme tablets incleaning contact lenses, as a rinsing solution followingcleaning and chemical disinfection, and as a lens

storage solution.

Thermal disinfecting units

The FDA guidelines require that thermal disinfectingunits must attain a minimum temperature of 80Cfor 10 min in the saline solution, which is placed inthe lens cases. There are several units on the market,which meet these requirements; they vary in theirtimetemperature profiles. Certain lenses such as thosebelonging to the FDA Group-4 classification (ionic,high-water-content lenses) do not withstand repeated

heat treatment and tend to discolor. In general, FDAGroup-4 lenses are not heat disinfected. Units on themarket today have a thermostat, which cuts off theelectrical current when a certain temperature isreached, eliminating the need for patients to switch itoff. However, malfunctioning of units occasionallydoes occur.

Units on the market today are much different fromthose available earlier. The first unit was analogous toa baby bottle warmer. Lenses were placed in a lenscase, which was placed in a reservoir of water in anelectrical heating unit. The temperature in the reservoirreached almost the boiling point of water and the time

for disinfection was 30 min. To ensure not only disin-fection but also sterilization of lenses, a unit was intro-duced capable of achieving 120C for 20 min to ensurecomplete elimination of vegetative organisms as wellas spores. This unit, however, was not successful sincethe high temperature was detrimental to many lenspolymers. The current trend is toward developing aheating unit, which reaches temperatures below 80Cbut ensures elimination of vegetative forms of ocularpathogens.



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Chemical Disinfecting Agents (Oxidizing

and Non-Oxidizing)

There are two categories of chemical disinfecting solu-tions: The first category comprises those containingnon-oxidizing chemical antimicrobial agents, whichare non-toxic at the concentration level used in theproducts. The second category constitutes those con-taining oxidizing agents, which are toxic at the levelused for disinfection but are degraded to a non-toxiclevel during the disinfection process over a course oftime or by use of a second step that involves a neutra-lizing ingredient. Disinfecting solutions containing oxi-dizing agents (specifically hydrogen peroxide) gainedpopularity among lens practitioners in the mid- tolate-1980s because of the absence of traditional preser-vatives, which often caused red eye and delayed hyper-sensitivity. However, the neutralizing solution usedwith hydrogen peroxide often contains preservativesthat can cause ocular reactions. Lens practitioners

liked the concept of hydrogen peroxide decomposingto innocuous water and oxygen. Fewer reactions havebeen observed with such products, but the long termtoxic effects on the eye of the free radicals which aregenerated by low concentrations of undergraded oxi-dizing agents are not well known. Hydrogen peroxideproducts can cause severe toxic reactions if the pro-ducts are not used properly and the patient inserts alens without neutralizing the hydrogen peroxide.

The ideal chemical disinfecting agent should possessthe following properties: It should have excellent wear-ers acceptance in terms of being non-irritating, non-sensitizing, and easy to use. It should be relatively

non-toxic compared to the earlier preservatives interms of cytotoxicity, including its effects on epithelialand endothelial cells as well as its ability to maintainmitotic activity of corneal epithelial cells. It must havean adequate antimicrobial spectrum and be able to elim-inate ocular pathogens in short lens-soaking regimens. Itshould not bind or bind minimally to the lens surface. Itshould be compatible with the lens and not cause discol-oration or alter the tint of colored contact lenses.

A hydrogen peroxide disinfection system for softlenses was tried initially in the early 1970s. The systemfailed to gain FDA approval because of the potentialtoxic nature of the chemical, the complexity of several

steps, and the cost. The system was approved by theFDA in the early 1980s after having undergone signifi-cant refinements compared to the original system.

All products currently marketed in the UnitedStates under the oxidizing agent category containhydrogen peroxide. In the international market, pro-ducts containing chlorine-releasing agents are alsoavailable. These products are generally indicated forthe disinfection of hydrophilic soft contact lenses andare contraindicated for rigid gas-permeable lenses.

Most of the hydrogen peroxide is decomposed bycatalytic degradation (platinum ring); chemical neutra-lization using pyruvate, sodium bisulfite, or sodiumthiosulfate; dilution and rinsing; and enzymatic neutra-lization (catalase).

Hydrogen peroxide, on degradation, forms waterand oxygen and, hence, it is perceived by practitionersas a superior product. However, most of the neutrali-zers used in the second step contain preservatives suchas thimerosal and sorbic acid, and stabilizers such asstannates or phosphonates. Consequently, they havethe associated disadvantages of those ingredients. Onthe other hand, not having a preservative in a neutralizermakes these products vulnerable to microbial growth onaccidental contamination. A single-stepproduct contain-ing hydrogen peroxide is also available on the market,which is convenient, but has the same disadvantage ofnot having any preservative effect at the end of the disin-fection cycle. The disinfecting time recommended byvarious companies ranges from 10 min to an overnight

soak. This category of disinfecting agents has a betterantimicrobial spectrum and a faster kill rate. However,their shortcomings included toxicity if the regimen wasnot followed properly, complexity of use, and zero tominimal protection against microbial recontaminationonce the disinfection cycle was complete.

The first generation non-oxidizing chemical disin-fection solution contained a combination of anti-microbial agents incorporating thimerosal withchlorhexidine or alkytriethanol ammonium chloride.These solutions are now not commonly used becauseof the thimerosal problems as discussed previously.The newer antimicrobial agents, Polyquad and Dymed,

because of their molecular structure and large moleculesize have a better profile. These antimicrobial agentswere introduced in the late 1980s and their long-termuse has not caused reactions similar to those observedfor older antimicrobial agents. Products with theseagents currently dominate the lens care market.

PRODUCTS FOR ENHANCING SOFT

CONTACT LENS WEAR COMFORT

Factors Contributing to Wear Comfort

It has already been noted that hydrogel contact lensesare inherently more comfortable that rigid (RGP orPMMA) lenses. This is related to the formers superiorflexibility and hydrophilic character which permitsincorporation of substantial amounts of water (3874%)into the lens material. However, after periods ofwear time, some lenses may experience changes inhydration, that may be related to deposits, environmental(e.g., temperature and humidity) changes and impropercare. In particular, dry spots may become evident on



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the lens with attendant reduction in comfort and visualacuity. When this happens, the wearer may benefit fromperiodic administration of rewetting (or soothing or com-fort) solutions onto the lens while being worn. These solu-tions are usually low-viscosity aqueous compositionscontaining polymers or surfactants, which enhance thewettability of the surface, facilitating the spreadingtears, and enhancing the stability of the tear film. Theymay also provide cushioning and lubricating actions, les-sening impact, and reducing the frictional forces of theeyelids as they move across thelens on thecorneal surface.The frictional forces would be especially important ininstances where deposits or debris on the lens are presentin sufficient amounts to cause physical irritation to theocular tissue. In addition to wetting, cushioning, andlubricating, the ability of the solutions to facilitateremoval of contaminants and retard further soilage arealso desirable attributes. It is also desirable, in terms ofconvenience to the lens wearer, that the frequency ofadministration of drops of the above-mentioned types

be minimal. Therefore, the use of polymers and surfac-tants that associate with the (deposited) lens and resistremoval by the rinsing action of the tears is called for(i.e., polymers and surfactants with good substantivity).

Although rewetting efficacy is usually the primaryrequirement for hydrogel lens wearers, all three actions(rewetting, cushioning, and lubrication) may be of con-siderable significance for RGP or PMMA lens wearers.The practitioner should seek to help the wearer find theproduct best suited for his or her specific comfortneeds. Solutions designed for hydrogel lenses generallyhave lower viscosities, whereas solutions for rigid hardlenses usually have higher viscosities. Although high

viscosities can be of distinct benefit in enhancing cush-ioning action, a solution that is too viscous can causeblurred vision and hinder normal lid movement to anundesirable extent.

Components of Lens Comfort Solutions

Among the polymers used in lens comfort solutions arepolyvinyl alcohol, polyvinylpyrrolidone, dextran, andvarious cellulose derivatives such as hydroxyethylcellulose, hydroxypropyl cellulose, and hydroxypropylmethylcellulose. Surfactants include certain poloxamer

and poloxamine compounds. Other normal compo-nents comprise appropriate preservative(s) as well asbuffering and tonicity-adjusting agents.

LENS CARE PRODUCTS FOR RIGID

GAS-PERMEABLE LENSES

Several types of RGP lenses are marketed (Table 2)and others are under development. Because of their

rigid nature, they have certain characteristics in com-mon with conventional hard PMMA lenses. In manycases, care products available for use with the latterhave been found to be also suitable for the care ofthe RGP lenses. Although they may not have optimalcharacteristics, they are still preferred by many practi-tioners in comparison to products that were originallydesigned for use with soft lenses and were subsequentlyapproved by the FDA also for use with RGP materials.

Most categories of products indicated for the careof soft contact lenses are applicable to rigid gas-permeable lenses. These include daily cleaners, wettingand cushioning drops, and weekly enzymatic cleaners.While disinfecting solutions are necessary for RGPlens care, they are often positioned as conditioningsolutions. Conditioning is important in providing ahydrophilic lens surface during wear. Because RGPlenses do not withstand heat, saline solutions (bothpreserved and unpreserved) are not needed for theselenses, except for dissolving enzymatic cleaners for

weekly cleaning or rinsing.Because RGP lenses are not as porous or waterabsorbing as soft lenses, wearers do not experiencethe problems that are specific to soft lenses, resultingfrom preservatives penetrating and concentratingwithin the lens polymer matrix, which often cause toxicand hypersensitivity-type reactions. However, certainpreservatives bind with RGP surfaces and can createclinical problems. Binding may involve ionic and/orhydrophobic interactions.

In addition to accumulation of proteinaceousdeposits, such as those occurring on soft hydrophiliclenses, the molecular make-up of many RGP lenses

also tends to attract lipid deposits, such as cholesterolesters, wax esters, triglycerides, etc. This is especiallytrue of the more hydrophobic materials such as siliconeacrylates with high Dk (oxygen permeability) values.Accordingly, more recent developments in materialscience related to contact lenses have resulted in mate-rials such as fluorosilicone acrylates and fluorocarbonswith purportedly less propensity for deposits.

Wearing rigid lenses is much less comfortable thanwearing soft contact lenses. In fact, this is generallyperceived to be the major factor limiting the growthof the RGP lens market segment. Consequently, theneed for superior wetting, cushioning, and lubricating

products is clearly recognized. Superior combinationproducts are also required for RGP lenses, which pro-vide convenience and enhance product performance.

MULTIPURPOSE SOLUTIONS

Multipurpose solutions are designed to increase wearercompliance and the convenience of product use. Suchsolutions are not commonly used for the conventional



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PMMA hard lenses and rigid gas-permeable lenses.They combine two or more basic functions of lens care,including cleaning, disinfection, soaking, wetting, andlubricating. Combination of these functions in a singleproduct may compromise certain aspects of productefficacy. For instance, a solution designed to cleanand disinfect may not clean as well the cleaner wouldalone. However, a combination cleaning and disinfec-tion solution provides the convenience of a single stepand would be particularly useful for wearers whoselenses do not attract deposits as readily because oftheir tear chemistry.

Multipurpose solutions for soft lenses are primarilylimited to cleaning and disinfecting. Wetting and lubri-cating combinations are not a major need because ofthe inherent hydrophilic nature of soft lenses thatmakes them comfortable to wear. The technologyadvances made in identifying preservatives withbroader spectrum and capacity along with the abilityof chemicals to clean while disinfecting has further sim-

plified care of lenses. Recently, a new product has beendeveloped in a multipurpose solution format that hasallowed removal of the rubbing step.

PACKAGING OF CONTACT

LENS PRODUCTS

All lens care products are packaged in plastic contain-ers or pressurized metal containers with the exceptionof enzymatic or disinfecting tablets. The tablets aregenerally effervescent and packaged in laminated foilor blister packs to ensure adequate shelf life. The pack-

aging materials normally used by the pharmaceuticalindustry for effervescent tablets are adequate for thispurpose. The plastic containers are usually fabricatedfrom low-density polyethylene, high-density polyethyl-ene, or polypropylene materials. Many of the contain-ers are opaque for protection against light. Severaltypes of colorant mixtures, which usually containtitanium, are used in squeeze bottles, and the compo-sition and thickness of the container wall should bedesigned to allow easy delivery. Another importantconsideration is the orifice at the tip, which allowsthe desired product to flow. For instance, a disinfectingor saline solution needs to be delivered in a large vol-

ume of 3 to 5 ml to fill the lens case. A steady streamis desirable and acceptable here, but not for productslike wetting, lubricating, and cushioning drops, whichare directly instilled in the eye. For these products,the tip has to be designed to allow drop-by-drop instil-lation. Formulation characteristics such as viscosityand surface tension determine the tip design. The tipmust be smooth and rounded as it can come into con-tact with the eye. The caps for the bottle are normallyconstructed of polystyrene or polypropylene material.

Because all lens care products, with the exception ofthe tablet dosage form, have to be sterile, the contain-ers must be sterilized prior to filling unless the processinvolves form, fill, and seal technology. Containers areusually sterilized by ethylene oxide or gammairradiation. The latter method is preferred because ofstringent government regulations and requirementsregarding ethylene oxide residues and its degradationproducts. Recent years have also seen strict controlsregarding the exposure of workers to ethylene oxideand its by-products. Terminal sterilization of the finalproduct is normally not done for lens care products,with the exception of non-preserved saline solutionsin aerosol containers, which are sterilized by gammairradiation.

ACCESSORY CONTACT LENS PRODUCTS

Accessory contact lens products include cases and

devices for cleaning contact lenses and facilitatinginsertion.

Lens Cases

Lens cases are utilized for disinfection and storagewhile the lenses are not being worn. Lens cases mayhave a single compartment with a barrel shape, gener-ally holding 7 to 10 ml of solution, or they may havetwo compartments in a flat case design, each compart-ment holding 3 to 5 ml of solution. Lens cases are alsoused by lens manufacturers as mailers to ship RGP andPMMA lenses in the dry state. Recently, shipping thelenses in conditioning solution hasbeen approved. Onthe other hand, hydrophilic soft contact lenses are gen-erally shipped in sealed sterile glassvials containingbuffered isotonic saline solution. Plastic lens cases arefabricated from polymeric materials such aspolyethy-lene, polypropylene, polysulfone, or polycarbonate.

Devices Facilitating Cleaning

Cleaning devices are useful for lens wearers who lackthe manual dexterity to clean lenses with their fingers.They are also used for cleaning lenses that could be

scratched easily by fingertips. The consumer versionsprovide mechanical action by manual swirling or byagitation with the help of an electrical motor or sonica-tion The professional versions are usually ultrasonic-type devices. None of these devices are capable ofremoving tenaciously bound protein. The reservoir ofthe cleaning device is filled with special cleaning fluidor a saline with a few drops of a surfactant-type dailylens cleaner. The device should allow easy lens place-ment and retrieval and minimize the potential of



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damage. Lens baskets that allow for rinsing after thecleaning regimen without additional handling are adesirable feature.

Devices Facilitating Lens Insertion

These devices are generally helpful to elderly patients,

especially those wearing aphakic lenses. They consistusually of a rubber bulb with a suction cup. Theycan cause severe corneal damage if used improperly aswell as ocular infection if they are not properly cleanedand disinfected.

Future Directions in Lens Care Products

Of the persons fitted with contact lenses (both soft andhard), 40% discontinue wearing them within the firstthree years. One of the reasons cited is the time andeffort required in taking care of them. Therefore, lens

care systems will be developed that are simple andmore convenient to use, requiring fewer products,and less time. The new products will minimize patientproblems through safer preservatives, which are non-toxic even on misuse and do not produce hypersensiti-zation. More effective cleaners as well as productswhich minimize protein and microbial attachment tolens surfaces will also be forthcoming as well as clea-ners that can be instilled in the eye during lens wearto retard deposit formation on extended-wear lensesor to clean lenses while they are being worn. Otherfuture product types may include special artificial tearsand comfort drops for older patients who are prone to

dry eye. There is also a need for diagnostic productsthat can detect potential problems before they aremanifested clinically. Universal products that couldbe used with all contact lenses (i.e., hard PMMA,RGP, and soft lenses) may be desirable; however, itis unlikely that such products will be available as dif-ferent contact lenses vary significantly in their chemicaland surface characteristics. The main emphasis in thefuture will be on the development of convenient,easy-to-use products that can increase patient com-pliance and reduce the dropout rate, while ensuringdesirable efficacy without compromising productsafety. Products specifically designed for the care of

disposable and frequent replacement lenses will alsobe forthcoming.

COMPONENTS OF LENS CARE PRODUCTS

Active Components

Active components play a primary role in the intendeduse of a product. The active components in lens care

products are usually limited to either one or twochemical entities. However, a product may containseveral active components if it is designed for multiplefunctions or indications.

Chemicals with disinfecting capability

Active chemical entities must have bactericidal andfungistatic properties. However, cidal properties forfungal organisms is preferable. The product perform-ance criteria encompassing the types of organisms tobe tested, levels of inoculum, and method of testingare defined by guidelines developed by the FDA. Cur-rent chemical systems have disinfection times of 46 h.This fits with most wearing schedules, because morethan 90% of patients remove their lenses overnightbetween wear periods. Overnight removal seems tohelp the eye recover from the stress of lens wear.Recently, some efforts to move to shorter disinfectiontime are under way to increase convenience. The

products will require dramatically enhanced disinfec-tion efficacy than currently available or strict com-pliance to a regimen to achieve the required level ofdisinfection.

Surface-active and other agents

with cleaning capability

Surfactants of various types have been traditionallyused for cleaning conventional PMMA hard lenses.They are considered effective in removing surfacedeposits on these lenses, such as cosmetics, hair spray,mascara, etc. However, they are not effective in remov-

ing tenaciously bound deposits (e.g., proteins, lipids,lipoproteins, mucoproteins) that are commonlyencountered with soft hydrophilic contact lenses andrigid gas-permeable lenses. Such deposits are moreeffectively removed by products containing enzymes,strong oxidizing agents, or suspended abrasive(deposit-shearing) particles. The types of surfactantsused and representative products on the market arediscussed later under Products for Cleaning Soft Con-tact Lenses. A few other agents such as citrate andsome phosphates have been used as cleaning agents.

Components with wetting, lubricating,

and cushioning capabilities

Polymers and surfactants are the two main classes ofcompounds used as wetting, lubricating, and cushion-ing agents. Contingent on the nature of the specifiedpolymers, they are used in various combinations toachieve desired product characteristics.

Both synthetic and natural polymers are commonlyused in lens care products. These agents can providea cushioning effect as a result of increased viscosity.



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IontophorLens

The need for products with such action is greater forthe wearers of conventional hard PMMA lenses andrigid gas-permeable lenses, for these are inherentlynot as comfortable as soft contact lenses because ofthe lens design and the physiochemical nature of thepolymers. Viscosity-building agents provide the neces-sary initial coatings on the lens surface before it iscoated by natural tear components. Besides contri-buting to viscosity, the ability of polymers to adsorbon lens surfaces and to elicit surface-active (wetting)properties are important considerations.

Surface-active agents are adsorbed on the lens sur-face and allow ready spreading of tears when the lensesare inserted, thus making them more comfortable towear. The use of surface-active agents to impart wett-ability to the lens surface is of lesser value for productsused for hydrophilic soft contact lenses, which havebuilt-in wetting characteristics because of their watercontent. Addition of surfactants may be of value, how-ever, in retarding deposit formation or for cleaning

while the lenses are worn. The methodology for mea-suring both advancing and receding contact angles,as an indication of wetting efficacy, has been standar-dized for contact lenses. Various polymers have differ-ent degrees of wettability as measured by contact angleusing a goniometer. However, the in vitro contact-angle measurement of contact lenses made fromvarious polymers is of little clinical value. No discern-ible differences in in vivo contact angle can be detectedon insertion of a contact lens in the eye following a fewblinks that result in coating the lens surface with tearcomponents. Surfactants are usually combined withpolymers to impart substantivity and cushioning char-

acteristics. The types of polymers and surfactants usedin representative products in the market are discussedlater under Products for Enhancing Soft Contact LensWear Comfort. Again, the need for surface-activeagents which can facilitate wetting of lenses andspreading of tears is greater for PMMA and rigidgas-permeable lenses because of their hydrophobicsurface characteristics.

Ancillary Components

Preservatives

Preservatives are used in almost all multidose contactlens products. Because the potential for misuse of pro-ducts by lens wearers is significant, preservatives pre-vent the potential proliferation of microorganisms. Acontaminated product could ultimately lead to an ocu-lar infection and possible loss of eyesight. Preservativesare considered active components when incorporatedin products for the purpose of disinfecting contactlenses. The preservative must possess the antimicrobial

activity described in the FDA guidelines for contactlens care.

The FDA has issued guidelines for preservative effi-cacy, which include an additional safety factor to com-pensate for potential misuse of products. Theserequirements are more stringent than the requirementsof the United States Pharmacopeia (USP) for preser-vative efficacy. The FDA requires rechallenging thepreserved products on day 14 with a defined inoculumof microorganisms; this is not required by the USP.The preservatives generally used are mainly the sameas those used for thermal or chemical disinfection ofcontact lenses. The concentrations could be differentthan in the chemical disinfection of contact lenses.The concentration is generally higher in cleanersand comfort-enhancing solutions because of possiblebinding with polymer and surfactant components,which result in a decrease in preservative efficacy.

Different countries have different standards for pre-serving contact lens solutions; the requirements of the

British Pharmacopeia are the most stringent. Manymarketed products do not meet these requirements.The three major preservative efficacy tests, which mustbe considered in developing products, are delineated inthe United States Pharmacopoeia (modified test to meetFDA guidelines), the British Pharmacopeia and theGerman Pharmacopeia (DAB). In terms of difficultyto comply, the British Pharmacopoeia test is the moststringent and the modified USP test the least stringent.The main differences among the test requirements arethe exposure times and use of Escherichia coli as achallenge organism. The British Pharmacopeia utilizesa 6 h criterion for antimicrobial activity, whereas the

USP uses a 14 day criterion. Recently, an InternationalStandard has been approved which is comparable tothe US FDA procedure. The types of preservatives usedare described in the tables related to various productcategories.

Buffers for adjusting pH

The use of buffers and pH adjustment is an importantconsideration in lens care products. It is a general prac-tice that all products which are likely to come in directcontact with ocular tissues should be buffered for ocu-lar comfort around physiologic pH and preferably in

the range 68.0. The most commonly used buffers incontact lens care products are phosphates and borates.Buffers used occasionally are acetate, citrate, andothers. Besides buffers, sodium hydroxide and hydro-chloric acid are generally used to achieve a desirablepH in the final product. They are also used to adjustthe final pH in products, which do not have any buffer-ing system. The selection of an appropriate bufferingsystem should consider the pH necessary for optimalperformance of the product, as well as products



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stability and potential incompatibility with othercomponents of the product.

Although it is desirable to have a product as close tophysiologic pH as possible, it is often essential to for-mulate a product outside the physiologic pH range inorder to achieve the desired stability of the product,optimal efficacy, or appropriate solubility of activeand ancillary components. Products formulated out-side the physiologic pH range should have low buffercapacity to allow quick equilibration to tear pH bythe bicarbonate buffer system present in the tears.The maintenance of pH close to physiologic pH isessential for products intended for soaking and disin-fection of hydrophilic soft contact lenses in order tomaintain the parameters of some lenses, especiallythose belonging to FDA Group-4. Such changes inparameters can cause not only discomfort but can alsoproduce blurred vision.

Tonicity-adjusting agents

Contact lens products should be formulated as closelyas possible to the tonicity of tears. This is importantfor optimal comfort. Prolonged exposure to hypotonicsolutions can induce edema in corneal epithelial cells,which can cause blurred vision and discomfort,whereas prolonged exposure to hypertonic solutionscan cause corneal epithelial cells to shrivel and causediscomfort by exposing nerve endings. None of thecurrently available contact lens solutions have beenresponsible for such symptoms as most of them areformulated close to isotonicity and many contact lensproducts have minimal contact with the cornea. Never-

theless, maintaining the tonicity of products close tothe isotonic value of 280 (50) mOsm/kg is importantfor optimal comfort as well as for maintaining theintegrity of certain hydrophilic soft contact lenses(especially those belonging to FDA Group-4). The typeof compounds commonly used for imparting isoton-icity include buffering agents, sodium chloride, potass-ium chloride, propylene glycol, mannitol, dextrose, etc.

Viscosity-building agents

Viscosity-building agents such as synthetic and naturalpolymers are used as active ingredients in solutions

providing comfort and rewetting products. However,they are also used as ancillary agents in contact lenscleaning products. These agents allow better cleaningof contact lenses by enhancing the contact of thecleansing agent with the soiled lens and by facilitatingthe process of rubbing the lens between fingers orbetween the palm of the hand and an index finger.Highly viscous or gel-type cleaners are also available.However, they are not very popular as they are difficultto rinse and may cause ocular irritation. The types of

polymers used as ancillary agents are the same as thoseused for solutions providing comfort or rewetting solu-tions.

PHARMACEUTICAL TECHNOLOGY

CONSIDERATIONS IN PRODUCT DESIGN

With few exceptions, contact lens products are sterilesolutions. The sterility requirements are importantbecause of the potential of sight-threatening ocularinfections. The sterility test procedures and passfailcriteria as described in the United States Pharmacopeiamust be met for FDA approval of contact lens pro-ducts. The technology practiced in the development ofpharmaceutical products, such as injectable and largevolume intravenous fluids, is generally acceptable, withsomewhat less stringent requirements for contact lenscare products because most of these products do notcome into direct contact with the eye (i.e., its interior

cells and fluids). Products that are packaged in unitdose containers or multidose pressurized aerosolcontainers do not have to be preserved. However,multidose products other than aerosol containersshould be preserved and should pass the FDA preserv-ative efficacy test. Manufacturers intending to developlens care products should consult with the FDA forthe latest guidelines.

Apart from solutions, there are other pharmaceuti-cal dosage forms for contact lens products that are lesscommonly used. They include gel- and suspension-typecleaners, powders, and tablet dosage forms for enzy-matic cleaners or disinfectants. All of these products

are formulated as sterile products with the exceptionof powders and tablets. These, however, must complywith USP requirements for bioburden with addedspecifications for absence of colony-forming units ofStaphylococcus aureus and Pseudomonas aeruginosaamong other organisms. The choice of components informulating these products is much more restrictivein comparison to pharmaceutical products intendedfor systemic or topical use because of the potential ofcausing irritation to the sensitive ocular tissues.

Chemical components must be non-irritating andcompatible with ocular tissue as well as with lenses.The choice of components for tablets, such as binding

and lubricating agents, is much more restrictive, asthese ingredients must be soluble and form a clear sol-ution when dissolved in saline solutions. Formulationcomponents generally used and acceptable for ophthal-mic products may be unacceptable for contact lensproducts, as many contact lens materials can concen-trate components used in contact lens products asmuch as several hundredfold. On insertion of thelenses, these ingredients are released in toxic levels tothe cornea, causing minor to severe ocular reactions.



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IontophorLens

The binding and release of ingredients can be furthercomplicated by the condition of the lens. For instance,thimerosal and chlorhexidine, commonly used ingredi-ents in contact lens products, concentrate differently innew, deposit-free lenses as compared to used lenseswith protein deposits on the surfaces. Appropriatestudies must be designed to address these issues tominimize the potential of ocular irritation. Certainingredients such as thimerosal, when used initially arewell tolerated. However, on prolonged exposure, somelens wearers develop hypersensitivity, resulting in intol-erance of thimerosal products. Such intolerance isdifficult to predict and currently no satisfactorymethod is available to predict delayed hypersensitiv-ity-type reactions, which are modulated immunologi-cally. The commonly used guinea pig maximizationtest is not predictive of delayed hypersensitivityreactions.

As noted previously, formulating products close tophysiological pH is desirable. However, for optimal

product performance or meeting regulatory require-ments, it is sometimes necessary to formulate productsoutside the physiologic pH range. Sorbic acid, a com-monly used preservative for lens care products, is amarginally effective antimicrobial agent with a pKavalue of 4.8. A product fails the FDA preservative effi-cacy test if it is formulated around a physiologic pH of77.4 at a concentration of 0.1 sorbic acid normallyused in marketed products. To maximize its antimicro-bial activity without compromising ocular comfort to asignificant extent, it is necessary to formulate such pro-ducts around pH 6.56.8. Thus, a consideration of thedissociation constants of preservatives is essential as

the antimicrobial activity of many preservativesdepends on the undissociated species, which shouldbe present in an adequate amount at physiologicalpH without causing ocular irritation.

The product design should also consider the natureof the lens polymer and its surface charges. Forexample, FDA Group-4 lenses, which carry negativesurface charges, can react with positively charged pro-duct components, resulting in severe ocular toxicreactions. Such toxic reactions can be prevented byincorporating non-ionic surfactants to form micelleswith the cationic components, thus minimizing surfaceinteractions and toxicity. If a cationic agent in the pro-

duct is a primary disinfecting agent, efforts to minimizetoxicity or surface interactions often result in reducedantimicrobial performance. It is, therefore, essentialto minimize surface interactions and yet have a pro-duct, which meets the requirements for disinfectionor preservation.

The hydrophiliclipophilic balance (HLB) and mol-ecular dimensions of a preservative should also beconsidered in the design of contact lens products. Forexample, chlorobutanol (a non-ionic preservative used

in ophthalmic products) penetrates into the matrix ofrigidgas-permeable (RGP) lens materials because ofthe molecules substantial lipophilic characteristics.The preservative present in the lens matrix may changetheparameters or may be gradually released duringwear, causing irritation and toxicity to the cornealcells. On the other hand, the molecular dimensions ofa preservative are very important in designing a pro-duct for hydrophilic, soft contact lenses. Generally,preservatives with a high molecular weight and appro-priate molecular configuration are less likely to pen-etrate the porous matrix of hydrogel lenses. Productscontaining preservatives like Dymed and Polyquad,with molecular weights above 1000, are currentlyavailable.

ACKNOWLEDGMENT

The authors wish to acknowledge the unstinting assist-

ance of Cathy Hughes in the preparation of this article.

BIBLIOGRAPHY

Bailey, N.J. Contact Lens Spectrum 1987, 2 (7), 631.Bennett, E.S.; Grohe, R.M. Rigid Gas-Permeable Contact

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British Pharmacopoeia 1988; [Appendix SVIC (Efficacy of Anti-microbial Preservatives in Pharmaceutical Products)]; HerMajestys Stationery Office: London, 1988; 2, A200A203.

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Dabezie, O.H., Jr., Ed.; Contact Lenses: The CLAO Guide toBasic Science and Clinical Practice, 2nd Ed.; Little, Brownand Company: Boston, 1989; Vol. 1 and 2.

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Houlsby, R.D.; Ghajar, M.; Chavez, G. J. Am. Optom. Assoc.1988, 59, 184188.

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Lippman, J.I. CLAO J. 1990, 16, 287291.Lowther, G.E. Preparations used with contact lenses. In Clinical

Ocular Pharmacology, 2nd Ed.; Bartlett, J.D., Jaanus, S.D.,

Eds.; Butterworths: Boston, 1989; 337353.MacKeen, D.L. Am. Pharm. 1986, NS26 (10), 2731.Mandell, R. Contact Lens Practice, 3rd Ed.; Charles C. Thomas:

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