A Mathematical Model for Ocular Tear and Solute Balance

Hui, Zhu; Chauhan, Anuj

doi:10.1080/02713680591004077

Cited by 49 publications

(24 citation statements)

References 39 publications

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“…This stimulated tearing would increase the rate of tear secretion. The experimental and model results were comparable when the tear secretion rate was increased by a factor of 3 to account for this tearing from irritation [40].…”

Section: Accepted Manuscriptmentioning

confidence: 83%

“…It is possible that this discrepancy is due to penetration of the compound into the ocular tissue, as the molecule has a smaller molecular weight than the cutoff reported for the cornea and conjunctiva [40]. Additional discrepancies between model and experiments were found when examining the rate of clearance of a…”

Section: Accepted Manuscriptmentioning

confidence: 93%

“…For this reason, the time for removal of the drug from the system is also over predicted, with experimental results taking 900-1000 s for a tracer compound in a 25 μL drop to reach 1% of its original value [48,49] while the model predicts this time to be 1454 s. Again, increasing the rate of evaporation would result in the model predicting a lower value. When the rate of evaporation was set at 4 times the value originally used in the model, the time for removal of the drug decreased by ~9% [40]. Finally, the concentration of the tracer compound in the tears was also measured over time.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

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Mechanistic modeling of ophthalmic drug delivery to the anterior chamber by eye drops and contact lenses

Gause

Hsu

Shafor

et al. 2016

Advances in Colloid and Interface Science

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Ophthalmic drug for the anterior chamber diseases are delivered into tears by either eye drops or by extended release devices placed in the eyes. The instilled drug exits the eye through various routes including tear drainage into the nose through the canaliculi and transport across various ocular membranes. Understanding the mechanisms relevant to each route can be useful in predicting the dependency of ocular bioavailability on various formulation parameters, such as drug concentration, salinity, viscosity, etc. Mathematical modeling has been developed for each of the routes and validated by comparison with experiments. The individual models can be combined into a system model to predict the fraction of the instilled drug that reaches the target. This review summarizes the individual models for the transport of drugs across the cornea and conjunctiva and the canaliculi tear drainage. It also summarizes the combined tear dynamics model that can predict the ocular bioavailability of drugs instilled as eye drops. The predictions from the individual models and the combined model are in good agreement with experimental data. Both experiments and models predict that the corneal bioavailability for drugs delivered through eye drops is less than 5% due to the small area of the cornea in comparison to the conjunctiva, and the rapid clearance of the instilled solution by tear drainage. A contact lens is a natural choice for delivering drugs to the cornea due to the placement of the contact in the immediate vicinity of the cornea. The drug released by the contact towards the cornea surface is trapped in the post lens tear film for extended duration of at least 30min allowing transport of a large portion into the cornea. The model predictions backed by in vivo animal and clinical data show that the bioavailability increases to about 50% with contact lenses. This realization has encouraged considerable research towards delivering ocular drugs by contact lenses. Commercial contacts are, however, not ideal for drug delivery due to the short release durations which may necessitate wearing multiple lenses each day, reducing the viability of this approach. Recent research has focused on designing contacts that retain all critical properties while increasing the release durations to a few hours or a few days. Beagle dog studies with contact lenses containing vitamin E nanobarriers to attenuate drug transport have shown promising results. Human studies using contacts for drug delivery have also been conducted for allergy therapy but drug eluting contacts are not available in the market for any therapy.

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Section: Accepted Manuscriptmentioning

confidence: 83%

Section: Accepted Manuscriptmentioning

confidence: 93%

Section: Accepted Manuscriptmentioning

confidence: 99%

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Mechanistic modeling of ophthalmic drug delivery to the anterior chamber by eye drops and contact lenses

Gause

Hsu

Shafor

et al. 2016

Advances in Colloid and Interface Science

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“…3 Because it rapidly dissolves, the tablet also minimizes discomfort associated with a macroscopic device and transiently provides increased viscosity to the tear fluid, which can facilitate local retention of the microparticles, giving them time to bind to the eye's mucosal surface. This drug delivery system was shown to release pilocarpine in vitro in a sustained manner for 3 hours after an initial burst of release within the first 10 minutes.…”

Section: Discussionmentioning

confidence: 99%

“…The use of liquid formulation eyedrops contributes significantly to this problem because it dramatically increases preocular tear film volume, which causes spilling from the eye, increased tear drainage, and dilution of the drug concentration. 3 For these reasons, large doses, often applied according to frequent administration schedules, are required, which can cause local side effects and undesirable systemic exposure as well as low patient compliance. To resolve these problems, a drug delivery system is needed that can stay on the surface of the eye for a prolonged period and thereby increase drug bioavailability.…”

mentioning

confidence: 99%

Mucoadhesive Microparticles in a Rapidly Dissolving Tablet for Sustained Drug Delivery to the Eye

Choy

Patel

Park

et al. 2011

Invest. Ophthalmol. Vis. Sci.

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PURPOSE.To test the hypothesis that mucoadhesive microparticles formulated in a rapidly dissolving tablet can achieve sustained drug delivery to the eye. METHODS. Mucoadhesive microparticles, smaller than 5 m were fabricated with poly(lactic-co-glycolic acid) and poly(ethylene glycol) as a core material and mucoadhesion promoter, respectively, and encapsulated pilocarpine as a model drug. These microparticles were embedded in a poly(vinyl alcohol) matrix to form a dry tablet designed to reduce rapid clearance of the microparticles on initial application to the eye. RESULTS. This in vitro drug release study exhibited that for all formulations, approximately 90% of pilocarpine was released during the first 10 minutes, and the remaining 10% was released slowly for 3 hours. In vivo mucoadhesion test on the rabbit eye indicated that mucoadhesive microparticles adhered significantly better to the preocular surface than other formulations. To assess the pharmacodynamics, the most prolonged pilocarpine-induced pupil constriction was observed in rabbit eyes in vivo using a tablet with mucoadhesive microparticles; it lasted up to 330 minutes. CONCLUSIONS. The authors conclude that mucoadhesive microparticles formulated into a dry dosage form is a promising system for sustained drug delivery to the eye. (Invest Ophthalmol Vis Sci.

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Drug release from liposome coated hydrogels for soft contact lenses: the blinking and temperature effect

Paradiso

Colaço

Mata

et al. 2016

J. Biomed. Mater. Res.

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In this article, liposome-based coatings aiming to control drug release from therapeutic soft contact lenses (SCLs) materials are analyzed. A PHEMA based hydrogel material loaded with levofloxacin is used as model system for this research. The coatings are formed by polyelectrolyte layers containing liposomes of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and DMPC + cholesterol (DMPC + CHOL). The effect of friction and temperature on the drug release is investigated. The aim of the friction tests is to simulate the blinking of the eyelid in order to verify if the SCLs materials coated with liposomes are able to keep their properties, in particular the drug release ability. It was observed that under the study conditions, friction did not affect significantly the drug release from the liposome coated PHEMA material. In contrast, increasing the temperature of release leads to an increase of the drug diffusion rate through the hydrogel. This phenomenon is recorded both in the control and in the coated samples. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1799-1807, 2017.

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A Mathematical Model for Ocular Tear and Solute Balance

Cited by 49 publications

References 39 publications

Mechanistic modeling of ophthalmic drug delivery to the anterior chamber by eye drops and contact lenses

Mechanistic modeling of ophthalmic drug delivery to the anterior chamber by eye drops and contact lenses

Mucoadhesive Microparticles in a Rapidly Dissolving Tablet for Sustained Drug Delivery to the Eye

Drug release from liposome coated hydrogels for soft contact lenses: the blinking and temperature effect

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