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Journal of Basic and Clinical Pharmacy


Novel Approaches in Formulation and Drug Delivery

using Contact Lenses

Kishan Singh, Anroop B Nair*, Ashok Kumar and Rachna Kumria

M.M. College of Pharmacy, M.M. University, Mullana, Ambala, India-133207.


The success of ocular delivery relies on the potential to enhance the drug bioavail- Contact lenses, ocular
ability by controlled and extended release of drug on the eye surface. Several new ap- delivery, drug loading,
proaches have been attempted to augment the competence and diminish the intrinsic controlled release
side effects of existing ocular drug delivery systems. In this contest, progress has been
made to develop drug-eluting contact lens using different techniques, which have the
potential to control and sustain the delivery of drug. Further, the availability of novel received on 18-04-2011
polymers have facilitated and promoted the utility of contact lenses in ocular drug modified on 05-05-2011
delivery. Several research groups have already explored the feasibility and potential of accepted on 10-05-2011
contact lens using conventional drugs for the treatment of periocular and intraocular available online 15-05-2011
diseases. Contact lenses formulated using modern technology exhibits high loading, www.jbclinpharm.com
controlled drug release, apposite thickness, water content, superior mechanical and
optical properties as compared to commercial lenses. In general, this review discus
various factors and approaches designed and explored for the successful delivery of
ophthalmic drugs using contact lenses as drug delivery device.


beta-cyclodextrin everal eye diseases like cataract, age-related
CDs Cyclodextrins macular degeneration, diabetic retinopa-
EGF Epidermal growth factor thy, glaucoma etc have reported to aect
GMA Glycidyl methacrylate several millions of the world population [1, 2].
HEMA Hydroxyethyl methacrylate Existing treatment modalities include topical, in-
ODDS Ophthalmic drug delivery systems troaocular and systemic delivery. The intraocular
PDMS Polydimethylsiloxane and systemic therapy is not widely used due to
pHEMA Poly-hydroxyethyl methacrylate their intrinsic limitations. However, the topical
scCO2 Super critical carbon dioxide route is the most appropriate therapy for local
SCLs Soft contact lenses and controlled delivery of bioactive and therapeu-
SSI Solvent impregnation tic molecules to the eye, as it oers higher patient
Tg Glass transition temperature compliance, better proximity to the infected site
and avoids potential systemic side eects as well
[3,4]. Among the topical formulations, conven-
tional topical eye drops is well accepted and rep-
resents ~70-90% of the marketed formulations.
However, the success of topical therapy is limited
*Corresponding Author:
Email: banroop@gmail.com by several issues such as low bioavailability (>1%),

Kishan Singh et al. Journal of Basic and Clinical Pharmacy

short residence time, low corneal permeabil- SNAGS IN OPHTHALMIC DRUG

ity, eective removal mechanisms and rapid loss DELIVERY
through nasolacrimal drainage [5, 6]. Further, There are several physiological barriers to diusion
frequent administration of high concentration of and productive absorption of topically applied drugs
medication from topical eye drops is extravagant in the precorneal and corneal spaces (Figure 1). The
and diminishes the patient compliance [7, 8]. precorneal restrictions responsible for poor ocular
Thus, the major challenge in ocular drug delivery bioavailability of conventional ophthalmic dosage
remains the controlled and extended delivery of forms are solution drainage, lacrimation, tear dilu-
medication in a therapeutically relevant concen- tion, tear turnover and conjunctival absorption. On
tration. Hence, the quest for developing systems instillation the drug mixes with the tear uid and
that can deliver eective concentration of drugs leaves the precorneal area within 2 min, is the key
in a comprehensive way was initiated [9]. Several factor in reducing the contact time of drug with cor-
approaches were designed and explored to aug- nea and consequently ocular bioavailability of topical
ment the therapeutic eciency of topically ap- dosage forms. The drug unabsorbed by the cornea is
plied ocular formulations and there by surmount either absorbed by the conjunctiva or ows through
the inherent limitations. Extensive studies were the upper and the lower canaliculi into the lacrimal
carried out to develop ecient ophthalmic drug sac [17]. The conjunctiva possesses a relatively large
delivery systems (ODDS) particularly to im- surface area, 5 times the surface of cornea making
prove therapeutic duration, targeting and compli- the loss signicant. Alternatively, tears dilute the
ance in a more predictable and reproducible way remaining drug in the cul-de-sac which subsequently
[10-12]. Consequently, few products including reduces the transcorneal ux. The drug entity, pH,
contact lenses, have been launched in the market tonicity of the dosage forms as well as formulation
while many others are in pre-clinical and clinical adjuvants can stimulate tear production which may
stages. These includes polymeric/mucoadhesive eventually dilute the formulation. Further, the drug
formulations, hydrogels, in situ gelling systems, containing tear uid is carried from lacrimal sac into
colloidal systems, ocular inserts, collagen shields, nasolacrimal duct, and is absorbed into the systemic
poly(tetrauoroethylene) strips, intravitreal im- circulation. However, the absorption of drugs into
plants, punctual plugs etc. [13-15]. bloodstream leads to depletion of chemical moieties
Commercial contact lenses are competent to and its existence in systemic circulation could leads
enhance the bioavailability however could not nd to undesirable side eects. For example, -blockers
their way in prolonging the drug delivery. The such as timolol, used in the treatment of wide-angle
potential application of contact lens as ODDS glaucoma, have a deleterious eect on heart. Thus,
was rst described by Sedlacek [16]. Contact lens- new ODDS such as contact lenses are primarily
es are particularly attractive for ODDS as these aimed to increase the residence time of the drug
signicantly increase the residence time (typically in the corneal region, and limiting the drug loss by
days) of the drug in the eye, high degree of com- drainage, lcarimation or conjunctival absorption.
fort and enhances the drug bioavailability consid-
erably. Survey of literature suggests that the soft ADVANTAGES
contact lens receives much attention in recent Several benets including increased ocular bioavail-
days as drug delivery device. Approaches such as ability, prolonged residence time, improved patient
incorporation of binding agents by molecular im- compliance, higher eciency and low side eects are
printing, entrapment of vesicular systems into the accounted for contact lenses in the literature, com-
lens matrix are found to be promising. Various re- pared to conventional dosage forms (Figure 2). The
search groups have focused on the development of soft contact lenses (SCLs) possess multiple advan-
contact lenses which can extend the residence time tages such as ease of application, convenient for long
in eye and thereby control the drug release for an term therapy due to their excellent biocompatibility,
extended period of time. This review discusses the provides continuous drug delivery, unproductive
recent developments in contact lens drug delivery systemic absorption, higher patient compliance etc.
for the eective and ecient delivery of drug to Indeed, medicated SCLs may combine the role of
the eye. ODDS with the correction of refractive deciencies.

Vol-002 Issue-002 May 2011 88 www.jbclinpharm.com

Journal of Basic and Clinical Pharmacy Contact lenses for ocular drug delivery

Figure 1: Fate of the drug administered on topical ocular application.

Figure 2: Schematic representation of drug release time for contact lenses and conventional
topical formulation.

www.jbclinpharm.com 89 Vol-002 Issue-002 May 2011

Kishan Singh et al. Journal of Basic and Clinical Pharmacy

Table 1: FDA approved silicon c ontact lenses and their manufacturers.

Extended wear Lens permeability

Manufacturer Application period Material % Water content
lenses (barrer) Dk

Night & Day Ciba Vision 30 days Lotrafilcon A 24 140

Pure Vision Bausch & Lomb 30 days Balafilcon A 36 99

O2 Optix Ciba Vision 7 days Lotrafilcon B 33 110

Acuvue Oasys Jonson and Jonson 7 days Galyfilcon A 36 103

Biofinity CooperVision 7 days Comfilcon A 48 128

However, contact lens loaded by soaking technique lens surface remains hydrophobic. Hence, the lens
possess few connes such as limited drug incorpo- surface is generally modied by plasma treatments
ration in lens matrix, incompetent to oer slow and which can alter the hydrophobic nature of the lens.
extended drug release, wastage of large fraction of On the other hand, few lens types have incorpo-
drug during loading procedure etc. [18]. However, rated internal rewetting agents to ensure the hy-
recent developments in techniques such as molecular drophilicity of the lens surface. A third process uses
imprinting and supercritical solvent impregnations longer backbone polymer chains that results in less
have surmounted all these issues [19]. cross linking and increased wetting without surface
alterations. Several companies are fabricating contact
POLYMERS IN OCULAR CONTACT lenses including four major manufacturers from the
LENSES United States (Table 1). At present, there are seven
The most popular type of ophthalmic lens is soft dierent disposable silicone hydrogel lens materials
contact lens made of thermo-set polymer hydrogels. commercially available in the United States which
These gels possess three dimensional, amorphous include balalcon A (PureVision, B&L), lotral-
networks with cross-links, similar to hard contact con A (Night & Day, CIBA Vision), galylcon A
lens polymers, and are typically produced by cast (Acuvue Advance, Vistakon), lotralcon B (O2Op-
molding or spin cast method [20]. The reason for tix, CIBA), senolcon A (Acuvue Oasys, Vistakon),
the softness of the lens is principally because these comlcon A (Bionity, CooperVision) and enlcon
polymers exist above its glass transition temperature A (Avaira, CooperVision). The lenses are prepared
(Tg). Otto Wichterle discovered poly-hydroxyethyl by dierent strategies, for instance, balalcon A is a
methacrylate (pHEMA) a hydrogel, in 1961and homogeneous combination of a tris[trimethylsiloxy]
created the worlds rst soft lens. In1971, FDA silylpropyl-methacrylate (TRIS) monomer deriva-
approved hydroxyethyl methacrylate (HEMA) tive that is copolymerized with the hydrophilic hy-
based contact lenses for daily wear. In 1999, sili- drogel monomer N-vinyl pyrrolidone. Lotralcon
cone hydrogels become available which are used to A involves polymerizing unmodied TRIS and
form the extended wear contact lenses that are per- macromers with silicone elastomer sequences inter-
meable to oxygen. Although it provides the oxygen spersed with hydrophilic polyethylene glycols, and
permeability, the presence of silicone makes the lens each lens is treated to create a hydrophilic surface.
surface highly hydrophobic and less wettable. This Both galylcon and senolcon are dierentiated from
frequently results in discomfort and dryness dur- the rst-generation silicone hydrogels (Balalcon
ing lens wear. Usually hydrogels are incorporated A and lotralcon A) because no surface treatment
to compensate the hydrophobicity, however, the is applied. Instead, in both the cases a long-chain,

Vol-002 Issue-002 May 2011 90 www.jbclinpharm.com

Journal of Basic and Clinical Pharmacy Contact lenses for ocular drug delivery

high-molecular-weight polyvinyl pyrrolidone was in- Seeking to improve soft contact lens permeabil-
corporated, which serves as an internal wetting agent ity scientist started to make hydrogels from silicone
for galylcon A (Hydraclear) and senolcon A (Hy- based polymers like polydimethylsiloxane (PDMS).
draclear Plus). Comlcon A (Bionity, CooperVi- The silicone hydrogel contact lens, also known as si-
sion) and enlcon A (Avaira, CooperVision) are the loxane lens, show impressive permeability (PDMS
latest silicone hydrogel entries. Both uses a unique has a Dk of 600 barres), while retaining the com-
long-chain siloxane macromer combined with other fort, wettability and biolm resistance of non-silicon
components to result in a lens that features high oxy- based hydrogels [26]. However, in order to avoid
gen permeability and a relatively low modulus [21]. hypoxia, an extended wearable contact lens must
These materials are inherently wettable and no inter- provide at least minimum oxygen transmissibility
nal wetting agent or surface treatment is required. (Dk/t) of 87 barrer, which may not be easy to at-
tain with traditional hydrophilic contact lens [24].
FACTORS AFFECTING DRUG Recently, one report suggested the minimum value
DELIVERY of Dk/t to avoid hypoxia as 125 barrer [27]. The re-
Transparency of the lens ported values of Dk of various commercial contact
Transparency of the formulated contact lens is a lenses are given in Table 1. With an approximate av-
key factor aecting the drug delivery, and cannot erage thickness of 80 mm, these commercial silicone-
be compromised due to the incorporation of drug hydrogel contact lenses can provide sucient oxygen
particles or additives. The novel approaches have transmissibility to be used as extend wear. Various
enabled to formulate and incorporate materials in researchers have used these extended wear contact
contact lenses which demonstrated good transpar- lenses for ophthalmic drug delivery with no eect on
ency. For instance, contact lenses formulated with the oxygen permeability of the lens [28-30].
advanced techniques such as molecular imprinting
and supercritical solvent approaches, loaded lipo- Glass transition temperature
somes and microemulsions, exhibited good trans- The Tg of contact lenses is not expected to alter dur-
parency [22, 23]. ing the drug loading process or due to incorporation
of additives. Several studies indicate that the contact
Oxygen permeability lenses manufactured by various approaches have not
Human eye does not receive adequate blood ow shown any signicant eect on Tg [31]. Further, the
to supply the eye with enough oxygen, or to re- alteration in Tg on addition of CD was found to be
move enough carbon dioxide. It mainly relies on its insignicant, which suggests that the grafted CD
exposure to the air for oxygen supply. Hence, the has little or no eect on the degree of cross-linking
prepared lenses should allow free transfer of oxygen of the hydrogels or the stiness of the network [32].
to the eyes and any low oxygen transfer eventually Costa et al also found that the Tg of contact lenses
causes severe side eects [24]. The lens permeability was not aected after the impregnation process and
(Dk) is the product of the diusivity (D) and the drug release [31]. Yanez et al reported no alteration
oxygen partition coecient (k), and it is typically in the Tg values of the SCLs with successive super
expressed in units of 10-11 (cm2/s)*(mlO2/(ml critical uid processing steps [33]. Thus, most of the
mmHg)) or 1011 mlO2 cm/(s cm2 mmHg), which methods used for the fabrication of contact lenses
is also referred as barrer or Fatt. The oxygen perme- have good feasibility of loading the drugs with no
ability is an intrinsic property of a material to trans- change in Tg.
port oxygen through its bulk and is independent of
thickness. The oxygen transmissibility refers (below Wettability
equation) to the oxygen transport capacity of a spe- Hydrophobic polymers will repel the water that
cic contact lens with thickness t, and it generally makes up a majority of the tear surface. This disrupts
expressed in units of 10-9 cm mlO2/(s ml mmHg) the tear ow and results in the deposition of an albu-
or 10-9 mlO2/(s cm2 mmHg) [25]. min lm on the lens, which eventually reduces the
eectiveness of the contact and can cause infection
and/or irritation [34]. Therefore, if a contact lens
surface is highly hydrophobic it needs to be made hy-

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Kishan Singh et al. Journal of Basic and Clinical Pharmacy

drophilic. Doping the polymer or treating the surface drug as shown by Kim et al [37]. The plausible rea-
of the polymer can do this change in the morphology son is that the hydrophobic drugs will partition into
of the surface. However, wettability of soft contact the silicone rich phases, and the partition coecient
lenses aects their physiological compatibility and of drug in the gels will be inuenced by the silicone
the stability of the pre-lens lacrimal uid and can be composition of the gels.
measured by contact angle measurements. For in-
stance, wettability of pHEMA was slightly increased APPROACHES FOR DRUG INCOR-
when copolymerized with high proportions of gly- PORATION
cidyl methacrylate (GMA), but slightly decreased Basically two approaches have been used to incor-
when CD was attached [32]. However, contact porate drugs into contact lenses; loading drugs into
lenses using -CD-loading can be used for extended preformed lenses, or manufacturing the lens with
drug delivery. On the other hand, no signicant ef- the drugs entrapped inside. Attempts were also
fect on the contact angle was measured when timolol made by dissolving drug in the monomer solution
maleate and acetazolamide was impregnated using and followed polymerization, incorporation of drug
supercritical solvent impregnation technique [31]. loaded nano or micro based vesicular systems into
The theoretical contact angles above 90 indicates the matrix, ocular inserts, ion exchange reaction with
non-wetting of the lens surface [35]. There are re- hydrogel functional groups etc. However, these tech-
ports in the literature which suggests that supercriti- niques increase the number of processing step and
cal uid based contact lenses keep their wettability are tedious for fabrication. Various research groups
properties after processing [33]. In addition to wet- have worked on novel approaches to enhance the
tability and content, the comfort of soft contact lens drug delivery into the cornea using the application of
also depends on the viscoelasticity of the network contact lenses, and are summarized in Table 2.
and on its sliding over the eye surface and the lids
[36]. All these results indicate that several process- Drug loading in preformed lenses
ing techniques could be used for the loading of drugs The success of ocular delivery using contact lenses is
in contact lenses without producing much eect on based on its ability to release the drug at controlled
the wettability. Further one should be aware that rate for an extended period of time. Traditionally,
contact lens should be highly hydrophilic and must contact lens are applied by soaking it on a drug so-
resist the deposition of a biolm on the lens, in the lution for a short duration and placed over the eye
case of extended wear. surface. However, the therapeutic eciency of the
commercial contact lens was not very successful and
Water content the treatment remains elusive. The major cause for
The permeability of the lens is proportional to this is due to the very low uptake of drug by the lens
the amount of water in the lens. As the percent and the rapid release which eventually leads to low
weight of water increases in the lens, the permeabil- residence time. Key limitations of soaking methods
ity increases linearly. The ability of lenses to absorb are the diusion of water into the polymer and drug
large amounts of water also makes them highly hy- aqueous solubility. At present, the modern manu-
drophilic. These attributes gives soft contact lenses facturing techniques could be utilized to formulate
the ability to achieve greater permeability and could extended wear contact lens (using silicone hydrogel)
be used for extended wear without disturbing the which are permeable to oxygen and can be worn for
eye. However, achieving greater permeability is a long duration. Using this as an advantage several
complex issue as increase in water content will even- contact lenses are fabricated and evaluated [28, 38].
tually loose the polymer strength. This can lead to Eciency of acuvue lenses was assessed after loaded
tearing or scratching of the lens. A softer lens also with lomeoxacin, by immersing it in commercially
oers the cornea less protection. Lenses with higher available eye drops and placing on the cornea of albi-
water content absorb more water soluble drug com- no rabbits. The drug concentration in the corneal and
pounds and releases it later into the tear lm than do aqueous humor levels of lomeoxacin in the eyes fol-
low water content lenses. Nevertheless, there is no lowing the wear of lomeoxacin-loaded lenses were
correlation exist between the amount of drug release found to be signicantly higher than those achieved
and the water content of the lens for hydrophobic by frequent-drop therapy [28]. Hehl et al reported

Vol-002 Issue-002 May 2011 92 www.jbclinpharm.com

Journal of Basic and Clinical Pharmacy Contact lenses for ocular drug delivery

that acuvue contact lenses could be the most feasi- Molecular imprinting is a polymer synthesis
ble drug delivery system for uoroquinolones [39]. technique exploiting template-medicated polymeri-
Further, Karlgard et al measured the uptake and zation mechanisms to produce synthetic macromo-
release of several drugs using commercially available lecular networks with tailored anity, capacity and
HEMA based and extended-wear silicone contact selectivity for a template molecule which is depicted
lenses (ACUVUE, OASYS, NIGHT & DAY schematically in Figure 3. This approach provides
and O2OPTIX), which showed rapid release (~10 a rational design strategy for the development of
min) of drug suggesting its failure as an extended therapeutic contact lenses with enhanced loading
drug delivery [40]. Similar results were observed by and delayed release. Using these strategies, hydro-
other researchers when the study was carried out gel contact lenses were designed which are capable
using ciprooxacin and dexamethsone [18, 41]. In of releasing hyaluronic acid at a controlled rate (~6
another attempt, Schultz and Morck [30] have ex- g/h for 24 h) [45]. Progress in the eld has leads
plored the feasibility of drug uptake and release us- to development of ODDS of low-molecular-weight
ing epidermal growth factor from dierent hydrogel therapeutics such as anti-glaucoma, antihistamines,
contact lenses in rabbit model. The results indicate antibiotics, anti-inammatories etc for the treat-
that epidermal growth factor can be delivered from ment of anterior eye disorders. Experimental work
some but not all hydrogel materials, suggesting that has also conrmed that macromolecular memory
silicon polymers are specic to drugs. and not structural dierences are highly responsible
for controlling drug release kinetics, compared with
NEWER APPROACHES non-imprinted systems [46]. Further, it is also found
The use of polymers with varying width of channels that the therapeutically relevant amount of drug can
in the matrix can control drug delivery rate which be loaded and released over an extended period of
remains eective for longer periods. In this contest, time, which allows the technique to be applied to
soft contact lenses are more preferred due to their daily-wear and extended-wear contact lenses.
potential of increasing bioavailability of ophthalmic
drugs [42]. Approaches like molecular imprinting, Particle-laden soft contact lenses
particle-laden soft contact lenses, barrier approach, Particle-laden hydrogels are promising approach
complexation have been proposed to improve the for ocular drug delivery and are expected to deliver
corneal drug delivery. The pros and cons of various the drugs at therapeutic levels for a period of time.
approaches are discussed below; It involves liposomes-laden, surfactant laden, biomi-
metic hydrogels and drug polymer lms coated with
Molecular imprinting hydrogels. It may be possible to use this system for
The concept of molecular imprinting within the gels both therapeutic drug delivery to eyes and the pro-
involves creation of macromolecular memory for a vision of lubricants to alleviate eye problems preva-
template molecule within a polymer network. The lent in extended lens wear [23]. Typically, they are
diusion of drug molecules from imprinted contact transparent and provide controlled drug delivery.
lenses can be inuenced by average mesh size, tem- Gulsen and Chauhan encapsulated the ophthalmic
plate size and drug-polymer chain interactions [43]. drug formulations in nanoparticles and dispersed
Manipulation of these variables can increase the par- these drug-laden particles in the lens material, such
tition coecient and slow down the release of drug. as p-HEMA hydrogels. This drug-laden p-HEMA
Indeed, zero-order or concentration independent hydrogels were synthesized by free radical solution
release kinetics is highly desirable from drug delivery polymerization of the monomers in presence of nan-
devices. This can be achieved by controlling the ther- oparticles and were found to control the drug release
apeutic loading, providing careful attention to the for few days [47]. Similarly, to reduce drug loss and
functional monomer, template ratio, the diversity side eects, it is proposed to encapsulate the oph-
of functional monomers, the polymer backbone and thalmic drug formulations in liposomes and disperse
network structure. Ali et al have demonstrated the the drug-laden liposomes in the lens material. Upon
potential of molecular imprinting to tailor therapeu- insertion into eye, the liposome-laden lens is likely to
tic release kinetics of ketotifen fumarate (MW=425) release the drug between air and lens and/or between
by imprinting process [44]. cornea and lens, thus provides drug delivery for ex-

www.jbclinpharm.com 93 Vol-002 Issue-002 May 2011

Table 1: Various approaches and drugs used for contact lens drug delivery.

S. No. Drugs used Polymers/contact lens Method of drug incorporation Inference

Kishan Singh et al.

Acetazolamide, timolol Demonstrated the feasibility of preparing balafilcon A contact lenses using scCO2,
1. Balafilcon A Discontinuous SSI methodology
maleate ethanol and water by SSI [31].
HEMA, zinc methacrylate, 1- or

May 2011
Acetazolamide or Bioinspired imprinted pHEMA-
2. 4-vinylimidazole, and N-hydroxye- Remarkable improvement in the performance as controlled release system [56].
Ethoxzolamide hydrogels
thyl acrylamide
HEMA + methacrylmide propyl Molecular imprinting is capable to store the anionic drug such as azulene based on
3. Azulene Molecular imprinting technique
trimethylammonium chroride ion-exchange reaction [57].
Soaked in 0.1% brimonidine Disposable contact lenses are able to uptake and release brimonidine tartrate in
4. Brimonidine tartrate Acuvue contact lenses
tartrate solution vitro [29].
PLGA film coated over pHEMA lenses sustained the release of drug, which can be
Ciprofloxacin, By ultraviolet light polymerization
5. PLGA films over pHEMA controlled by changing either the ratio of drug to PLGA or the molecular mass of the
fluorescein film coating process
PLGA used [50].
Lotrofilcon A, etrafilcon A, All materials released the drug too quickly to be effective as drug delivery device
6. Ciprofloxacin HCl Soaked in 0.3% ciprofloxacin-HCl
balafilcon A [41].
Alphafilcon A, lotrafilcon A and Soaked in 0.1% dexamethasone None of the materials released drug for long period of time to be clinically useful as

7. Dexamethasone
galyfilcon solution a drug delivery device [18].
ACUVUE, OASYS, NIGHT & DAY Soaking of vitamin E loaded lens in Vitamin E loading increases the drug release by 9 to 16 fold than non vitamin E
8. Dexamethsone
and O2OPTIX drug solution loaded lenses [37].
-CD was grafted to the gel net- The hydrogels with pendant -CD are particularly useful for the development of
9. Diclofenac sodium pHEMA and GMA
work and soaked in drug solution. cytocompatible drug loaded SCLs [32].
Imprinting of contact lens by su- Shorter process time than those using conventional aqueous-based molecular
10. Flurbiprofen Hilafilcon B
percritical fluid-assisted method imprinting methods [33].
Flurbiprofen, timolol Nelfilcon A, omafilcon A methafil- SSI can be considered as a viable, safe, and efficient method for impregnation of
11. Discontinuous SSI methodology
maleate con A and hilafilcon B. drugs [19].
Bactericidal concentrations were found up to 3 days after contact lens fitting in all
12. Gentamicin HEMA with 38.6% water content Soaking in 0.5% drug solution
human subjects [38].
Soaking in 1 mg/ml and 5 mg/ml Gentamicin concentrations attained via the MTL exceeded the mean inhibitory
13. Gentamicin Morgan therapeutic lens (MTL)
solutions concentration for most sensitive bacterial species in rabbits cornea [58].
Gentamicin, Kanamycin,
Soaking of lenses in 0.3% drug It releases sufficient amounts of gentamicin, ciprofloxacin and ofloxacin to produce
14. Tobramycin Acuvue contact lens
solutions bacteriostatic concentrations in the aqueous humor in cataract patients [39].
Ciprofloxacin, Ofloxacin
Dispersion of hexadecane micro- p-HEMA gels loaded with a microemulsion, stabilized with silica shell are
15. Hexadecane pHEMA
imuslsion in contact lenses transparent and releases drugs for a period of over 8 days in vitro [22].

Journal of Basic and Clinical Pharmacy
HA can be delivered from a disposable lens at a therapeutic rate of approximately 6
16. Hyaluronic acid (HA) Nalfilcon A Molecular imprinting technique
g/h for 24 h [45].
Imprinting via living polymerization extends or delays the template release profile
Ketotifen, diclofenac HEMA, acrylic acid, acrylamide Gels prepared by living /controlled
17. by two-fold over that of imprinting via conventional free-radical polymerization
sodium and methacrylic acid imprinting technique
techniques [43].

Bitelechelic methacrylated
polydimethylsiloxanes macrom-
onomer, 3-methacryloxypropyltris
18. Ketotifen fumarate Pre-soaking in drug solution Sustained ketotifen fumarate was released for more than 24 h in rabbits eye [59].
(trimethylsiloxy)silane, and N,N-
dimethylacrylamide using ethylene
glycol dimethacrylate
Journal of Basic and Clinical Pharmacy

Soaked in commercially-available
19. Lomefloxacin Acuvue contact lens Releases sufficient amounts of lomefloxacin for up to 8 h (Rabbits eye) [28].
0.3% lomefloxacin eye solution
Imprinted hydrogels synthesized using norfloxacin: acrylic acid (1:3 and 1:4) molar
20. Norfloxacin pHEMA with acrylic acid Mollecular imprinting technique ratios showed the greatest ability to control the release process, sustaining it for
more than 24 h [60].

pHEMA, HEMA, mono-methacr-

The data demonstrate that pHEMA/-CD hydrogel contact lenses can effectively
21. Puerarin ylated -CD (mono-MA--CD) and Prepared by photopolymerization
deliver puerarin through the rabbits cornea [61].
trimethylolpropane trimethacrylate

Incorporation of methmethacrylate as comonomer increases the timolol loading
HEMA+ methacrylic acid or meth-
22. Timolol Molecular imprinting technique capacity to therapeutically useful levels while retaining appropriate release charac-
teristics in vitro [62].

N-N-diethyllacrylamide, meth-
Timolol loading capacity of the contact lenses as well as sustaining of drug release
23. Timolol acrylic acid, ethylene glycol Molecularly imprinted technique
was improved by the molecular imprinting method [63].

N,N-dimethylacrylamide, 3-me
Timolol, dexametha- iloxy)silane, bis-alpha, omega-
Soaked in different drug solutions The mechanical and physical properties of lenses of the hydrogels are suitable for
24. sone, dexamethasone- (methacryloxypropyl) polydimeth-
concentrations contact lens application [49].
21-acetate ylsiloxane, 1-vinyl-2-pyrrolidone,
and ethylene glycol dimethacr-

Timolol, fluconazole,
Soaking of vitamin E loaded lens in Increased the release time of drugs but vitamin E loading have slight effect on the
25. dexamethason-21- NIGHT&DAYTM lens
drug solution mechanical property of lens [25].

Contact lenses for ocular drug delivery

May 2011
Kishan Singh et al. Journal of Basic and Clinical Pharmacy

Figure 3: Schematic draw of recognition site for drug molecule made by using molecular
imprinting process.

tended periods of time. In another study, dimyris- Barrier approach

toyl phosphatidylcholine liposomes are dispersed in Another approach for the controlled release of drug
p-HEMA hydrogel contact lenses and the results in- moieties from contact lenses is by in situ creation of
dicate the prepared lenses are transparent and exhib- transport barriers. This diusion barrier can be any
ited controlled release (~8 days). Further, the deliv- solid or liquid material that is impermeable to oph-
ery rates can be modied by controlling particle size thalmic drugs. However, the prerequisite is that the
and drug loading [23]. Alternatively, drug delivery barrier could be dispersed within the lens material
from contact lenses can be controlled by formulating in a manner that keeps the lens transparent. Sev-
microencapsulation. Gulsen et al embedded micro- eral ophthalmic drugs are charged at physiological
emulsion drops in p-HEMA hydrogels, stabilized pH and so hydrophobic molecules will likely form
with a silica shell, which were found to be transpar- eective barriers. It is also important to ensure that
ent and provided controlled release for >8 days. Ka- the barrier material is biocompatible so that diu-
poor and Chuhan have developed surfactant-laden sion of the compound from the barrier into the tear
p-HEMA contact lenses of cyclosporine A for the lm does not cause toxicity. Kim et al developed ex-
controlled release using various Brij surfactants and tended wear silicone hydrogel soft contact lenses that
evaluated the inuence of chain length and unsatu- deliver ophthalmic drugs for an extended period of
rated groups on drug release. The results indicate time ranging from weeks to months. Contact lenses
that surfactant-laden p-HEMA gels are potential comprising of N, N-dimethylacrylamide, 3-meth-
for extended release of cyclosporine A, and possess acryloxypropyltris (trimethylsiloxy) silane, bis-alpha,
suitable mechanical and optical properties for con- omega-(methacryloxypropyl) polyethyl, 1-vinyl-2
tact lens applications [48]. All these studies points to -pyrrolidone, and ethylene glycol dimethacrylate
the fact that particle-laden hydrogels could be con- were formulated using varying ratios of monomers
sidered as one of the most promising approaches for and evaluated for the drug diusion of timolol, dex-
the successful delivery of ODDS. amethasone, and dexamethasone 21-acetate from

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Journal of Basic and Clinical Pharmacy Contact lenses for ocular drug delivery

Figure 4: Schematic representation of CD pendent hydrogel matrix.

the silicone hydrogels. The results from these studies ever, vitamin E uptake may increase the size of the
indicate that these polymers provides diusion lim- contact lenses but there is ~8% increase in wet di-
ited transport [49]. ameter when ~40% of vitamin E is incorporated,
Prototype, drug-eluting contact lenses were which is likely to be tolerated by human eyes. On
designed by coating poly(lactic-co-glycolic acid) the other hand, incorporation of vitamin E has lead
(PLGA) lms containing uorescein or ciprooxacin to extend the drug release to 7 to 9 days, which is 9
with pHEMA by ultraviolet light polymerization. to 16 fold more as compared to the dexamethasone
The results demonstrated controlled release of the release from pure contact lens, devoid of vitamin E
molecules with zero-order release kinetics for over 4 [37]. All these observations give initiative for the
weeks. Thus, it is benecial to use drug-PLGA lm use of vitamin E loaded contact lenses for control-
coated with pHEMA as a platform for controlled led and extended delivery of both hydrophobic and
and sustained release with widespread therapeutic hydrophilic drugs.
applications in ocular drug delivery [50]. Vitamin-E
which is a hydrophobic liquid has potential benets Cyclodextrin for controlled drug delivery
as biocompatibility and therapeutics, is recently used Cyclodextrins (CDs) are cyclic oligosaccharides with
as the diusion barrier. Drugs with dierent physi- hydrophobic cavity and form inclusion complex with
cochemical properties such as timolol, dexametha- several drug moieties through reversible non-cova-
sone 21-disodium phosphate and uconazole were lent interaction, and have shown success in ODDS
widely investigated. The data demonstrated that as well. The activity of CDs in liquid formulations is
loading of 10 and 40% vitamin E increases the re- limited as the decomplexation is instantaneous; how-
lease time of timolol by a factor of about 5 and 400, ever, in a polymeric network the release of the drug is
respectively. Similar results have been obtained for controlled. By forming the inclusion complexes they
other hydrophilic drugs including uconazole and may load a drug eciently and their release could
dexamethasone 21-disodium phosphate [25]. How- be sustained for several days. In addition, pHEMA

www.jbclinpharm.com 97 Vol-002 Issue-002 May 2011

Kishan Singh et al. Journal of Basic and Clinical Pharmacy

hydrogels were prepared by copolymerization with facilitates the diusion of the drugs into the poly-
glycidyl methacrylate at various proportions and mer matrix and act as a swelling agent or plasticizer
then beta-cyclodextrin (-CD) was grafted to the for polymers, thus increasing the free volume. In
network by reaction with the glycidyl groups under addition, utilization of cosolvents can augment the
mild conditions. This led to networks in which the overall process by increasing the drug solubility or
-CDs form no part of the structural chains but they by increasing the swelling and plasticization. On the
are hanging on 2-3 ether bonds through the hydroxyl whole, the amount of drug incorporation can be con-
groups. The schematic representation of the -CD trolled by altering the operational pressure, process-
loaded polymer matrix is shown in the Figure 4. ing temperature and selecting an apposite solvent.
However, the data observed suggests that grafted The supercritical solvent impregnation (SSI)
-CD does not alter the Tg, swelling, optical trans- technique has already proved its signicance in the
parency, or oxygen permeability of the network, but development of drug impregnated polymeric mate-
enhanced the drug loading (~1300%) and drug an- rials, which may have applications in drug delivery
ity (~15 fold). These contact lenses showed extended through therapeutic contact lenses. SSI allows the
release for 2 weeks in lacrimal uid with no leakage drug impregnation/dispersion of most polymeric
in the conservation liquid of contact lenses [32]. Xu articles and, when properly employed, without alter-
et al have prepared pHEMA/-CD hydrogel mem- ing and/or damaging their physical, chemical, and
branes and contact lenses by photopolymerization of mechanical properties and without degrading their
HEMA, mono-methacrylated -CD (mono-MA- constituent drugs, additives and polymers. Further,
-CD) and trimethylolpropane trimethacrylate by SSI proved to be a tunable process since the variation
cast molding process and assessed the release pattern of the employed operational conditions indicated
of puerarin (a chinese extract to alleviate glaucoma that it is possible to control the amount of impreg-
and ocular hypertension). The data suggests that the nated drug [19]. Moreover, this technique provides
drug loading and in vitro release rate were dependent the opportunity to incorporate both hydrophilic and
on -CD content in the pHEMA/-CD hydrogels hydrophobic drugs into the contact lens. Two dier-
and exhibits greater bioavailability, long residence ent methods of super critical carbon dioxide (scCO2)
time in tear uid of rabbit eyes when compared to impregnation/deposition of drugs were explained as
pHEMA contact lenses and eye drops [51]. These
results shows that the hydrogels with pendant cyclo- a) Supercritical uid deposition or dispersion:
dextrins are particularly useful for the development In this scCO2drug mixture will not really
of cytocompatible medicated implants or biomedi-
dissolve in the polymeric material but will
cal devices, such as drug-loaded soft contact lenses
as they does not signicantly alter the Tg, swelling, diuse into the existing pores of the material.
optical transparency or oxygen permeability of the On venting, the drug will nucleate, grow and
network with increase in drug load. precipitate as solid particles inside the pores
but only on the surfaces of the polymeric ma-
Supercritical solvent impregnation
Drugs may also be impregnated and dispersed into terial and may not be molecularly dispersed
polymeric matrixes by dissolving them in com- inside the polymer.
pressed high volatile uids (like carbon dioxide) at b) Supercritical uid impregnation (or supercriti-
temperatures and pressures near or above their criti- cal solvent impregnation): - In this scCO2
cal temperatures and pressures, and contacting the
drug mixture will dissolve in the polymeric ma-
resulting mixtures with those polymeric matrixes.
This may removes the limitations of conventional terial, promoting its inner plasticization and/
methods, like the possible use of toxic organic chemi- or swelling. On venting, the drug will nucleate,
cals, drug/solvents dissolution and compatibility is- grow and precipitate both inside the pores (at
sues, undesired drug reactions, drug photochemical
their surfaces, not molecularly dispersed) and
and thermal degradation, low incorporation yields
and heterogeneous drug incorporation/dispersion inside the previously swollen polymeric mate-
[52, 53]. However, the compressed uid mixture rial (molecularly dispersed) [19].

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Journal of Basic and Clinical Pharmacy Contact lenses for ocular drug delivery

Recently, Costa et al evaluated the eects of nature CONCLUSION

and concentration of cosolvents (ethanol and water) Progress in the eld of contact lenses drug delivery
on the impregnation eciency and the properties of has been established recently with controlled loading
the contact lenses [31]. The results showed that nal and sustained release. Dierent techniques have been
impregnation yield increases with the incorporation used for increasing the drug load and controlled re-
of co-solvent due to the increase in solubility of the lease. Each technique may have some pros and cones
drug with no eect on the oxygen permeability, wet- with little eect on mechanical and optical properties
tability and the Tg of contact lenses. Thus, SSI can of the lens. Various lens materials and their require-
be consider as a viable, ecient and safe alternative ment for ophthalmic use, also have eect on the drug
for the impregnation of drugs, including those of hy- loading. Experimental works demonstrated that the
drophobic character or presenting low aqueous solu- contact lenses exhibit greater drug loading with ade-
bility, into commercially available soft contact lenses quate mechanical and optical properties. The type of
by using cosolvents. the contact lenses and the technique of drug loading
are found to aect the residence time of the drug. In
Clinical Investigations comparison with topical alternatives, contact lenses
Several studies in human have been conducted to provide an increased residence time at the surface of
evaluate the novel contact lenses. In one attempt, Busin the eye for ecacious therapy.
and Spitznas have assessed the activity of hydrogel
bandage contact lenses (61% HEMA and 38.6% water CONFLICT OF INTEREST
content) soaked overnight in commercially available There are no conicts of interest.
sterile gentamicin solution (0.5%), and placed on
eyes of healthy adult volunteers. The results indicated
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