Topical drug delivery is nothing new and dates back to several thousand years ago. First appearing in ancient Mesopotamian records around 3000-3500 BC., topical drug delivery has since evolved into the more sophisticated solutions we see today. Nowadays, most topical drug products are semisolids, such as gels and creams, administered by licensed medical professionals, rather than the historical medicinal salves doled out by high priests.
Despite the advances made, however, successfully delivering topical therapeutics to the target tissue is still not always an easy endeavor. The skin, the most common site of action for topicals, is the largest organ in the human body consisting of complex layers (see Figure 1) inherently designed to keep foreign bodies and potential pathogens out. Successful pharmaceutical companies need to not only address this challenge to develop a topical product, but they also need to navigate an increasingly crowded market.
Today, consumers are demanding more out of their products, especially regarding aesthetic and sensory properties. In this post, Lubrizol Life Science Health (LLS Health) discusses the importance and benefits of topical drug delivery, as well as how these sensory properties are influencing topical development and differentiation. LLS Health then reviews the significance of the FDA's Inactive Ingredient Database (IID) and the components needed to create a topical drug with patient-centric attributes.
Figure 1. Illustration of layers of the skin
What are the benefits and significance of topical drug products?
Topical semisolids can effectively deliver therapeutics to a targeted area. Topical drug products consist of an API dissolved or dispersed into a carrier base with selected excipients to achieve the desired functionality. These semisolids primarily include gels (water-soluble bases), emulsions (water-in-oil or oil-in-water bases), and ointments (oleaginous or absorption bases). Conventional non-topical dosage forms, such as oral solids, are increasingly plagued with formulation and patient compliance issues, such as low bioavailability, inconvenient and/or frequent administration, and systemic side effects. These downsides are creating growth for solutions featuring alternative routes of administration.
Topicals benefit from convenient application/dosing and reduced risk of systemic side effects. Due to these advantages, it should come as no shock that this area is rapidly growing; In recent years, topical semisolids have secured a healthy position in global markets, with worldwide business expected to reach $123 billion by 2024, up from $93 billion in 2020.
In addition to market reports, emergent clinical research supports the prediction that topicals will play an increasingly important role in first-line therapy. For example, a recent Rheumatology and Therapy review investigating the topical application of diclofenac for osteoarthritis concluded that topical delivery of NSAIDs offered a "guideline-supported, generally well-tolerated, and effective first-line treatment option for knee and hand osteoarthritis."
Specifically, the study determined that multiple head-to-head trials demonstrated that topical NSAID delivery provided "at least equivalent analgesia, improvement in physical function, and reduction of stiffness compared with oral NSAIDs in osteoarthritis," with "fewer systemic adverse events." Although this review represents a delineated perspective focusing on a specific drug type, it provides a compelling case study supporting topical drugs' core value proposition. These products can provide effective, localized therapy that is easier for patients and associated with fewer systemic concerns.
Figure 2. Quote on topical prevalence
What are some trends in topical drug delivery, especially regarding sensory properties?
Drug manufacturers looking to develop semisolid products should be aware of market dynamics shaping the playing field. A rising trend is increasing patient expectations regarding organoleptic properties (i.e., those acting on or involving the use of the sense organs) and other "experiential" attributes. Organoleptic properties are playing a more significant role in topical pharmaceutical development; previously, these were only crucial to consider in personal care products like facial lotions and body wash. Formulating drug products with these characteristics in mind can make topicals more comfortable, seemingly effective, and aesthetically appealing for a consumer.Patients are progressively realizing this fact and choosing products that offer these additional sensory benefits. As the market becomes more crowded, consumer-focused properties such as this are taking a front seat in terms of product differentiation and increasing patient compliance. For example, clinical studies assessing patient preferences for dermatologic topicals may shine a light on sensory properties' importance. A 2017 study, published in the Journal of the European Academy of Dermatology and Venereology, noted that:
Poor adherence to topical therapies remains a significant problem; indeed, some studies have reported adherence rates of just 40%–70%. […] Adherence is influenced by multiple factors, which can be patient, disease, or treatment-related. Treatment‐related reasons include lack of efficacy, excessive time applying the medication and poor cosmetic characteristics.
Another study, published in the Journal of Dermatological Treatment in 2018, discovered that "attributes belonging to the formulation and application domains were greatly valued over attributes related to the container."These findings support the importance of a product's sensory properties in driving patient behavior and decision-making. Therefore, in addition to developing a safe and effective product, successful topical formulators will focus on a product's broader organoleptic attributes. A product's sensory properties, including aesthetics, skin feel, and ease of application, are crucial for shaping patient experience and helping a product stand out from heavy competition, subsequently increasing product sales.
What excipients are needed to create a desirable sensory profile, and how does IID listing play a role?
Several formulation components comprise a standard chassis for topical semisolids. These ingredients include rheology modifiers, emulsifiers, co-solvents, surfactants, buffers, chelating agents, preservatives, stabilizers, permeation enhancers, bioadhesive polymers, emollients, humectants, and structurants, among others. Relative to each other and the product's active ingredient, each can play an essential role in efficacy and the creation of a favorable sensory profile.
Many ingredients required to achieve this type of profile are included in the FDA's Inactive Ingredient Database (IID). According to the FDA, once an inactive ingredient has appeared in an approved drug product, the excipient is no longer considered novel for that particular administration route, dosage form, and maximum daily intake level and will appear on the IID.
IID-listed status is often a desired ingredient trait for topical developers. Formulators can be reluctant to use novel excipients in a drug product as there is no certainty the FDA will deem the available safety information on an excipient adequate when it comes time for product approval. However, once an excipient is listed in the IID, establishing safety and precedence of use, it requires a less extensive FDA review the next time a similar product includes it.
Lubrizol Life Science offers many IID-listed ingredients that can help improve topical pharmaceutical formulation performance. Lubrizol's Carbopol® polymers, Noveon® polycarbophil, and Pemulen™ polymers are well known for enhancing topical products. Lubrizol also offers IID-listed emollients, emulsifiers, and humectants with a long history of use in over-the-counter (OTC) and prescription drug products (Table 1).
| Table 1. Examples of Lubrizol IID-listed topical excipients | ||
| Excipient Type | Definition | LLS Health Examples |
|---|---|---|
| Emollient | Used to impart lubrication, spreading ease, texture, and softening of the skin. Emollients also counter the potentially drying or irritating effects of surfactants |
|
| Emulsifier | Used to stabilize an emulsion. An emulsion is a thermodynamically unstable system comprising two or more immiscible liquids, one of which is dispersed in the other |
|
| Humectant | Promote the retention of moisture on the skin. This increased moisture can increase an active ingredient's solubility, which can then in turn increase skin penetration |
|
The bottom line
Topicals today play an increasingly important role in first-line therapy, as they can have significant benefits over systemic routes of administration. However, with this enhanced importance comes amplified demands from consumers and the need for differentiation in a highly competitive market. Patients seeking topical products have high expectations regarding sensory and aesthetic properties, influencing the market and how formulators are making their products "stand out from the crowd."
Manufacturers that overlook important patient-centric formulation components risk losing business in a market abundant with product options. The key to securing long-term success for a topical drug product is to invest in meeting consumer needs, which means formulating with the optimal look, feel, and application of the product in mind. The best way to achieve these properties is through strategic excipient selection trusted, IID-listed excipients. These ingredients may require less extensive FDA review when included in a new product.
Lubrizol Life Science offers a wide variety of emollients, humectants, and emulsifiers listed in the FDA's IID, based on their usage in prescription drug products (Table 1). Additionally, these ingredients also have a long history of use in OTC products. Lubrizol Life Science ingredients play crucial roles in optimizing patient experience and organoleptic properties. These properties impact consumer perception and, therefore, can improve compliance in topical products. Contact Lubrizol Life Science today to learn more.
Authors:
Jim Baxter | Global Technical Service Manager
Ashley M. Rein | Technical Marketing Specialist
