To Issue 130
Citation: Lee R, “Keeping up with the Demand for Effective Ophthalmic Drugs”. ONdrugDelivery, Issue 130 (Mar 2022), pp 8–10.
Robert Lee explores the growth of the ophthalmic drug market and discusses the challenges that pharma companies may face when creating drugs to treat some of the most common ocular indications.
“Developing effective ophthalmic products is no simple task and challenges often come in the form of formulation issues and the need to identify suitable delivery methods.”
With rising public awareness of eye-related diseases and an ageing population, the demand for treatments for ocular conditions has dramatically increased. The global ophthalmic drug market has seen significant growth as a result. Its value was estimated to be US $28,400 million (£20,800 million) in 2020 and is expected to increase further to $36,300 million by 2025.1–3 The rising incidence of glaucoma and age-related macular degeneration (AMD) in particular have been identified as key factors driving the predicted expansion.
Of the 2.2 billion people affected globally by ocular conditions, AMD (170 million), cataracts (94 million), glaucoma (7.7 million) and diabetic retinopathy (DR) (3.9 million) are the most common.4 Some common ophthalmic conditions, including glaucoma, impact the front portion (anterior) of the eye, whereas others, such as DR and AMD, affect the rear portion (posterior) of the eye. Drugs used to treat these conditions will therefore need to reach the target area of the eye, resulting in different delivery requirements.
More and more pharma companies are keen to develop new ocular drugs as a result. However, developing effective ophthalmic products is no simple task; challenges often come in the form of formulation issues and the need to identify suitable delivery methods. Pharmaceutical companies will need to find a way to navigate these challenges throughout product development to ensure market success.
Fortunately for pharma companies seeking to take advantage of the growth in the sector, there is no need to face the challenges of ophthalmic drug development alone. One of the keys to success is identifying and partnering with contract development and manufacturing organisations (CDMOs) that have extensive ophthalmic drug development experience and expertise to support pharma companies on their manufacturing journey.
“Compared with anterior eye treatments, drugs requiring delivery to the posterior of the eye are often even more challenging.”
UNDERSTANDING ANTERIOR EYE TREATMENT NEEDS
Drug delivery methods targeting the anterior section of the eye are often topical, commonly relying on dosage forms such as eye drops and topical ointments. Anterior delivery treatments are easy to administer and are the most widely available ophthalmic treatments. Despite their popularity, however, there are many challenges surrounding topical ophthalmic treatments, such as their ability to penetrate the cornea or stay on the eye long enough to achieve efficacy.
The bioavailability of APIs delivered in the form of eye drops has been reported to be as low as 5–10%.5,6 One reason for this is that the conjunctival sac capacity is typically lower than the treatment volume, leading to a large proportion of the liquid running off from the eye area. Blinking and innate solution drainage also mean that the drug is often removed from the target area before it can be absorbed. The corneal and conjunctival epithelia additionally act as natural barriers, further limiting drug absorption.
Frequent administration to achieve the desired effect may be needed to compensate for low efficacy of the drug product. However, this has the potential to lead to toxicity, reduced patient compliance and increased costs. With careful formulation, residence time on the eye can be prolonged.
This can be achieved using delivery systems that offer muco- or bioadhesive properties, such as solid lipid nanoparticles, micelles and liposomes. Excipients such as carbomers, polycarbophil or sodium alginate can also establish bioadhesion.
“The methods used to manufacture implantables vary considerably and include solvent-based methods, injection moulding and hot-melt extrusion.”
INJECTIONS OR IMPLANTS FOR POSTERIOR EYE TREATMENT
Compared with anterior eye treatments, drugs requiring delivery to the posterior of the eye are often even more challenging. Posterior-targeting medicines generally need to reach the retina – a layer of cells critical for sight. As this currently cannot be achieved via topical administration, injections or implants are often used to deliver drugs to the back of the eye.
One of the main challenges associated with parenteral ophthalmic drugs is maintaining an effective concentration within the vitreous humor for a significant portion of time. Fluid clearance mechanisms limit the duration of the effect of drugs, necessitating further injections. However, treatments are invasive and uncomfortable for patients, so any method that can reduce frequency is highly desirable.
CONSIDERATIONS WHEN DEVELOPING IMPLANTS
Implantable drug delivery to the eye is highly attractive, due to sustained release potential, but can pose many challenges in development.7 Implants can either be bioresorbable (absorbed by the body over time) or biodurable (do not break down and typically require removal and/or refilling following initial treatment). Careful consideration must be paid as to which polymers to use to provide these properties.
The methods used to manufacture implantables vary considerably and include solvent-based methods, injection moulding and hot-melt extrusion. However, not all APIs are compatible with these methods. Throughout hot-melt and injection-moulding methods, APIs are often exposed to high temperatures and shear. Some drugs cannot tolerate these stresses without degradation occurring. Determining the best method for the API will require a thorough understanding of these manufacturing techniques.
Expert formulation could also allow for processing temperatures to be lowered to reduce API stress or switching to solvent-based processes to reduce degradation. However, solvent-based methods are not without their challenges and care must be taken to ensure that the API is compatible with the selected systems to minimise degradation.
THE BENEFITS OF EXPERT SUPPORT
The many challenges involved in designing both anterior and posterior ophthalmic treatments, and the rising complexity of their delivery systems, necessitate development and manufacturing by experts. Therefore, it is essential to partner with a CDMO with extensive experience of working with ophthalmic drug products. An ophthalmic drug development partner should be able to offer the expertise, capabilities and facilities necessary to help overcome the obstacles involved. A CDMO partner should also provide access to a portfolio of polymers, including implantable, biodurable polymers and mucoadhesive excipients, and have robust sterile manufacturing facilities.
REFERENCES
- “Ophthalmic Drugs Market Worth $47,600.6 million by 2030: Visiongain Research Inc”. Press Release, VisionGain Ltd, Jul 15, 2021.
- “Global Ocular Drug Delivery Devices Market Expected to Grow at a CAGR of 5.3% During 2021– 2027 – ResearchAndMarkets.com”. Press Release, ResearchAndMarkets, Nov 15, 2021.
- “Ophthalmic Drugs Market Size, Share & Trends Analysis Report By Disease (Dry Eye, Eye Allergy, Glaucoma, Eye Infection), By Drug Class, By Dosage Form, By Route Of Administration, By Product Type, By Region, And Segment Forecasts, 2021–2028”. Market Analysis Report, Grand View Research, Feb 2021.
- “Blindness and vision impairment”. Fact Sheet, WHO, Oct 14, 2021.
- Scruggs J, Wallace T, Hanna C, “Route of absorption of drug and ointment after application to the eye”. Ann Ophthalmol, 1978, Vol 10(3), pp 267–271.
- Prausnitz MR, Noonan JS, “Permeability of cornea, sclera, and conjunctiva: a literature analysis for drug delivery to the eye”. J Pharm Sci, 1998, Vol 87(12), pp 1479–1488.
- “Ocular Implants Market Size, Share & Industry Analysis, By Product Type (Intraocular Lenses, Glaucoma Implants, Ocular Prostheses, Corneal Implants, and Others), By End-user (Hospitals, Ophthalmic Clinics, and Others), and Regional Forecast, 2019–2026”, Industry Report, Fortune Business Insights, Mar 2020.