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Multidose Preservative Free Eyedrops by Selective Removal of Benzalkonium Chloride from Ocular Formulations

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Abstract

Purpose

About 70% of eye drops contain benzalkonium chloride (BAK) to maintain sterility. BAK is an effective preservative but it can cause irritation and toxicity. We propose to mitigate ocular toxicity without compromising sterility by incorporating a filter into an eye drop bottle to selectively remove BAK during the process of drop instillation.

Methods

The filter is a packed bed of particles made from poly(2-hydroxyethyl methacrylate) (pHEMA), which is a common ophthalmic material. We showed that pHEMA particle prepared by using ethoxylated trimethylolpropane triacrylate as crosslinker can be incorporated into a modified eyedrop bottle tip to selectively remove the preservative as the formulation is squeezed out of the bottle. Hydraulic permeability of the plug is measured to determine the resistance to eye drop squeezing, and % removal of BAK and drugs are determined.

Results

The modified tip has a hydraulic permeability of about 2 Darcy, which allows eyedrops formulations to flow through without excessive resistance. The tip is designed such that the patients can create an eyedrop of solution of 1–10 cP viscosity in 4 s with a nominal pressure. During this short contact time, the packed particles removed nearly 100% of benzalkonium chloride (BAK) from a 15 mL, 0.012% BAK solution but have only minimal impact on the concentration of contained active components.

Conclusion

Our novel design can eliminate the preservative induced toxicity from eye drops thereby impacting hundreds of millions of patients with chronic ophthalmic diseases like glaucoma and dry eyes.

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Abbreviations

∆P :

Pressure drop across the bed

A :

Cross-sectional area of the bed

BAK:

Benzalkonium chloride

CMC:

Carboxymethyl cellulose

Da:

Darcy (=0.9869233 (μm)2)

H :

Length of the packed bed

HEMA:

2-hydroxyethyl methacrylate

k :

Hydraulic permeability of the packed bed

pHEMA:

Poly (hydroxyethyl methacrylate)

SR454HP:

Ethoxylated (3) trimethylolpropane triacrylate

SR9035:

Ethoxylated (15) trimethylolpropane triacrylate

UVB:

Ultraviolet B (280–315 nm)

μ :

Fluid viscosity

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ACKNOWLEDGMENTS AND DISCLOSURES

The work reported here is a part of a pending utility patent which is licensed to TearClear.

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Authors and Affiliations

  1. Department of Chemical Engineering, University of Florida, Gainesville, Florida, 32611-6005, USA

    Kuan-Hui Hsu, Karishma Gupta, Harish Nayaka, Aashrit Donthi, Siddarth Kaul & Anuj Chauhan

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  1. Kuan-Hui Hsu
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  2. Karishma Gupta
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  3. Harish Nayaka
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  4. Aashrit Donthi
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  6. Anuj Chauhan
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Correspondence to Anuj Chauhan.

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Hsu, KH., Gupta, K., Nayaka, H. et al. Multidose Preservative Free Eyedrops by Selective Removal of Benzalkonium Chloride from Ocular Formulations. Pharm Res 34, 2862–2872 (2017). https://doi.org/10.1007/s11095-017-2270-8

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  • DOI: https://doi.org/10.1007/s11095-017-2270-8

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