iPatch: An Opthalmic Drug Delivery Device for Administering Dexamethasone to Post–Surgical Cataract Patients

Charul Singh, Nehal Jolly, Serena KaplanArizona State University

Mentor: Dr. Brent Vernon, Associate Professor, SBHSEINTRODUCTION

MISSION STATEMENT

FINAL PROTOTYPE DESIGN

REFERENCES

PROBLEM ANALYSIS

Cazzini, Karl. “Juxtascleral drug delivery and ocular implant system” Google Patent Web. 2011. Chauhan, Anuj. “Contact lens based bioactive agent delivery system” Google Patent Web. 2009. Ciolino, Joseph B., Cristina F. Stefanescu, Amy E. Ross, Borja Salvador-Culla, Priscila Cortez, Eden M. Ford, Kate A. Wymbs, Sarah L. Sprague, Daniel R. Mascoop, Shireen S. Rudina, Sunia A. Trauger, Fabiano Cade, and Daniel S. Kohane. "In vivo Performance of a Drug-eluting Contact Lens to Treat Glaucoma for a Month." Biomaterials: 432-39. Print. Ciolino, Joseph B. "Patent US8414912 - Contact Lens Drug Delivery Device." Google Books. Web. 12 Nov. 2015. Dixon, P., Shafor, C., Gause, S., Hsu, K., Powell, K., & Chauhan, A. (n.d.). Therapeutic contact lenses: A patent review. Expert Opinion on Therapeutic Patents, 1117-1129 Guzman-Aranguez, Ana, Basilio Colligris, and Jesús Pintor. "Contact Lenses: Promising Devices for Ocular Drug Delivery." Journal of Ocular Pharmacology and Therapeutics: 189-99. Print. Kim, Jinah, Anthony Conway, and Anuj Chauhan. "Extended Delivery of Ophthalmic Drugs by Silicone Hydrogel Contact Lenses." Biomaterials: 2259-269. Print. Kim, Jinah, Cheng-Chun Peng, and Anuj Chauhan. "Extended Release of Dexamethasone from Silicone-hydrogel Contact Lenses Containing Vitamin E." Journal of Controlled Release: 110-16. Print. Ki, Seon Ho. "Therapeutic Contact Lens." Google Patents. Web. 12 Nov. 2015. Kohane, Daniel S. "Contact Lens Drug Delivery Device." Google Patents. Web. 12 Nov. 2015. Liu, Pei-Ling. "Drug Carrying Contact Lens." Google Patents. Web. 12 Nov. 2015. Liu, Dean-Mo. "Method for Fabricating a Drug-carrying Contact Lens." Google Patents. Web. 12 Nov. 2015. Lowery, Andrew. Medical Device Quality Systems Manual: A Small Entity Compliance Guide. Vol. First Edition. FOREWORD, 1996. Print. Peng, Cheng-Chun, Michael T. Burke, Blanca E. Carbia, Caryn Plummer, and Anuj Chauhan. "Extended Drug Delivery by Contact Lenses for Glaucoma Therapy." Journal of Controlled Release: 152-58. Print. Peng, Cheng-Chun, Jinah Kim, and Anuj Chauhan. "Extended Delivery of Hydrophilic Drugs from Silicone-hydrogel Contact Lenses Containing Vitamin E Diffusion Barriers." Biomaterials: 4032-047. Print. Patent EP2370054A2 - Contact lens drug delivery device. (n.d.). Retrieved October 29, 2015. Robinson, Michael. "Contact Lens as a Sustained Drug Delivery Implant." Google Patents. Web. 12 Nov. 2015. Springate, Chris. "Methods and Compositions Comprising Biocompatible Materials Useful for the Administration of Therapeutic Agents." Google Patents. Web. 12 Nov. 2015. Sato, Takao. “Ophthalmic lenses capable of sustained drug release and preservation solutions therefor” Google Patents. Web. 2015. Ulrich, K., & Eppinger, S. (1995). Product design and development. New York: McGraw-Hill. Xinming, Li, Cui Yingde, Andrew W. Lloyd, Sergey V. Mikhalovsky, Susan R. Sandeman, Carol A. Howel, and Liao Liewen. "Polymeric Hydrogels for Novel Contact Lens-based Ophthalmic Drug Delivery Systems: A Review." Contact Lens and Anterior Eye: 57-64. Print. Yuan, Xiaoyong. "Ocular Drug Delivery Nanowafer with Enhanced Therapeutic Efficacy." Web. 29 Oct. 2015.

ACKNOWLEDGEMENTS

DRUG RELEASE VALIDATION STUDY

The project was supported by the School of Biological and Health Systems Engineering of Arizona State University. Special thanks to Dr. Brent Vernon, Dr. Vincent Pizziconi, Dr. Michael Caplan, as well as the teaching assistants and the facilitators.

MARKET STRATEGY

CONCLUSIONS

To develop and deliver an innovative solution that helps to eliminate the current barriers in effective ophthalmic drug delivery, while consistently meeting the customer’s needs and expectations.

The polymer and drug conjugate was injected into bovine pericardial tissue using a commercial professional permanent makeup machine. The device was fitted with a single prong needle and a needle cap, which was adjusted to allow 1mm of the needle tip to extend past the cap. The formulation was then injected into the tissue samples with the needle oscillating at 100Hz (i.e. 100 penetrations per second). Gentle pressure was applied to the tattooing machine in order to deposit a small amount of the formulation into the tissue. An estimate of around 5uL was injected into each sample.

Polymer and Drug Conjugate Formulation:0.1g PDLG 5004

0.9g DMSO40mg Dexamethasone

Images from left to right: injecting polymer and drug conjugate onto tissue, cutting injected portion from tissue sample, drug release samples

1) Common diffusion equation2) Boundary condition3) Initial condition4) Initial drug distribution within polymer structure5) Hydrolytic degradation

Dexamethasone released from PDLG 5004 showed an initial burst release with ~30% of the total drug released within the first 3 hours. Steady-state release was observed from 3 hours to 7 days. Dexamethasone continued to release at a slower non-steady-state rate for up to 9 days.

iPatch aims to meet the compelling clinical complication that prevents people from effectively administering their prescribed drug dosage. After surgery, cataract patients are generally prescribed eye-drops by their doctor in order to prevent inflammation and infection. However, of the 3 million cataract surgeries that happen every year in the United States alone, over 47% of the prescribed dosages are omitted. To help prevent the issues caused by patient non – compliance, iPatch is a tissue based ophthalmic drug delivery device. This self – administering device will deliver polymer bound dexamethasone to post – surgical cataract patients at a sustained and controlled rate over a period of 7 days.

• None of these patents have been translated to products currently available on the market.• Drug delivery time with these devices is less than one week and they are not suitable for

long-term wear.• These devices are constructed from hydrogel materials and they all cover the entire visual

axis of the eye.

Eye drops account for 90% of all ophthalmic drug delivery applications, however there are significant barriers to effective drug administration with this method:• Forgetfulness• Dislike of administering eye drops• Educational barriers • Inability to self administer

Kass and associates demonstrated that all 20 cataract patients in their study on a specific medication regimen revealed non-compliance. The total

number of drops over the 14-day evaluation period should have been 70, but the average actual dosage by patients was just 33 drops

Eye drops have a short residence time in the eye and the drugs have low bioavailability to the eye with only 1-5% of the drug in the drops penetrating the eye. It has been shown that the bioavailability of drugs in the eye increase when drugs are delivered through extended release devices rather than through eye drops showing 50% drug uptake from the devices.

Market Size3.6 million people in US and 20 million

worldwide undergo cataract surgery annually.

Distribution ChannelsDistributed and

marketed to physicians

FDA Approval Pathway

Combination Device, PMA

Manufacturing Cost

$7.90 per unit

Projected Year 4 Net Present

Value$32,975,000

Marketed Price$75

Final Design• A rectangular patch made of bovine pericardial tissue that is placed

directly over the incision site. The patch is infused with the PDLG–5004/Dexamethasone formulation and coated with a thin adhesive layer.

• Drug delivery rate of the device is 0.229 mg/dayFindings• The device would be considered to be a combination product according to

the United States Food and Drug Administration regulatory policies.• Alpha, beta, and gamma prototyping demonstrated promising results for

ophthalmic drug delivery though the tissue based device.• Drug release assays tested via the UV/Vis spectroscopy showed that PDLG–

5004 bound Dexamethasone can be released from the bovine pericardial tissue at a sustained and controlled rate for a period of 7 days.

• The burst release seen during the initial few hours of the study can be resolved by washing off the excess drug from the surface before storing and distributing the product.

• The total amount of drug released by the device can be increased by increasing the ratio of drug to polymer in the formulation used for injection.

• The tensile strength testing showed that the bovine pericardial tissue base of the iPatch is much stronger than the regular soft contact lenses available on the market.

Future Work• Cytotoxicity testing in order to completely understand the biocompatibility

of the iPatch• Research for a suitable adhesive layer• Completion of the Abbreviate New Drug Application• Phase I, Phase II, and Phase III clinical trials