Adhesive drug delivery is gaining traction due to its ease of use and steady dosing. But with this promise comes a host of regulatory and development challenges that many sponsors fail to account for. From skin adhesion to combination product requirements, these complexities can quickly derail development timelines.

This blog breaks down five key challenges in adhesive drug development—and how the right partner can help you overcome them with confidence, speed, and clarity.

Why Traditional Expertise Doesn’t Translate

For many pharmaceutical teams, adhesive systems are an unfamiliar territory. Expertise in tablets, capsules, and injections doesn’t easily translate to transdermal or transmucosal administration, and adhesive systems require the active ingredient to maintain stability while embedded in a polymer matrix.

This means new formulation considerations, new testing methods, and new manufacturing challenges. Without the right experience, it’s easy to underestimate what’s required or miss critical risks early in development.

READ MORE: Adhesives and Drug Delivery: How Stick-On Solutions Are Advancing Therapeutics

Challenge #1: API Stability in the Adhesive Matrix

The Problem

When active ingredients interact with adhesive components, stability issues can emerge. While API stability is important in all dosage forms, adhesive systems face unique challenges as the API must remain stable while dispersed within polymeric materials, often for years and under varying storage conditions.

In transdermal patches, the API must not only maintain long-term stability during storage (2-3 years) but also remain stable throughout the product’s functional lifetime. This extended exposure creates conditions where moisture, oxygen, and temperature fluctuations can trigger degradation pathways specific to adhesive formulations.

READ MORE: Transdermal Administration Routes for Drug Delivery: A Short Guide

The Solution

Development specialists address this through comprehensive compatibility screening before full-scale formulation development. They apply predictive models based on previous adhesive-API combinations and implement specialized stabilization techniques like custom adhesive chemistry modifications or protective excipients that shield the API from degradation pathways.

Challenge #2: Achieving Reliable Adhesion Performance

The Problem

For skin-applied systems, adhesion impacts therapeutic effectiveness. The entire surface area of the adhesive must maintain skin contact throughout the intended wear while accommodating movement, sweat, bathing, and varying skin types.

The ideal adhesive provides sufficient initial tack for application, sustained adhesion during the wear time period, comfortable removal without skin damage, and minimal irritation—all while remaining compatible with the drug substance. This balancing act requires sophisticated formulation science that accounts for the skin’s natural variability.

With mucoadhesive systems like buccal films, the challenge escalates. These formulations must bond rapidly and continuously to moist mucosal tissues while resisting premature disintegration.

The Solution

Specialized partners draw from extensive polymer libraries explicitly engineered for biomedical applications. They employ testing methods that predict real-world performance, allowing for rapid optimization before expensive clinical studies begin.

Challenge #3: Overcoming Biological Barriers

The Problem

The skin’s protective barrier can limit the permeability of drug delivery. The stratum corneum effectively blocks the diffusion of most compounds through the skin, especially those with larger molecular sizes or poor lipid solubility.

Developers must enhance drug penetration without compromising skin integrity. This often requires specialized ingredients that temporarily modify the skin’s structure to allow drug passage. However, these permeation enhancers bring additional challenges—potential irritation, impacts on adhesive performance, and increased regulatory scrutiny.

For mucosal delivery routes, different barriers exist. While more permeable than skin, mucosal tissues have specialized structures and constant fluid secretion that can dilute the drug, reducing absorption.

The Solution

Experienced partners employ advanced approaches tailored to the delivery route and drug properties. These include optimized excipient combinations, multilayer designs that create favorable concentration gradients, and adhesive chemistries that complement the drug’s physicochemical profile to maximize therapeutic effect.

Challenge #4: Managing Manufacturing Complexity

The Problem

Scaling adhesive drug delivery systems from lab to commercial production introduces technical challenges unique to these products. Manufacturing requires specialized processes including precision coating, controlled drying, lamination of multiple layers, and die-cutting—each step introducing potential variability.

Coating thickness affects drug content and release rates, while drying conditions influence adhesive performance and drug distribution. As production scales up, heat and mass transfer dynamics shift significantly, potentially altering drug release profiles and adhesive properties.

The Solution

Dedicated manufacturing facilities help eliminate the technical compromises of adapted equipment.

Specialized partners understand the dynamics that occur between lab and commercial processes, utilizing decades of experience in the scale-up of transdermal and transmucosal drug delivery systems. These specialized partners offer advanced coating technologies, precision layer control systems, and tightly regulated environmental conditions that maintain critical quality attributes throughout scale-up. 

These production lines ensure consistent performance from development batches to commercial manufacturing.

Challenge #5: Developing Appropriate Testing Methods

The Problem

Evaluating adhesive delivery systems requires testing approaches beyond standard pharmaceutical methods. Physical properties like adhesive strength and tack directly affect therapeutic outcomes, yet aren’t captured by typical quality control parameters. 

USP General Chapter <3> “Topical and Transdermal Drug Products—Product Quality Tests” outlines peel adhesion testing, tack testing, and other specific tests that industry must reference and use when developing these dosage forms.

Drug release testing presents challenges as standard dissolution methods don’t accurately model the interface between the delivery system and the biological surface. Additionally, analytical testing becomes more complex due to the need to extract and separate the drug from the polymer matrix—a process that differs significantly from methods used for conventional dosage forms and requires specialized expertise.

The Solution

Experienced partners develop and validate specialized analytical methods for adhesive delivery platforms. Their established testing protocols link physical performance to therapeutic outcomes, providing meaningful data for development decisions and regulatory submissions.

Selecting the Right Development Partner

When developing adhesive drug delivery systems, your choice of partner has a direct impact on the success of your product. Look for specialized expertise in three key areas:

1. Formulation Science Expertise

Top-tier drug delivery partners offer deep knowledge in adhesive formulation, backed by a strong command of polymer science. Look for teams with expansive libraries of pharmaceutical-grade adhesives—each with varied chemical compositions designed to meet diverse therapeutic needs.

Experienced formulators can quickly identify adhesive systems that are compatible with your API, based on its chemical structure and stability profile. Using predictive modeling, they pinpoint potential interactions before lab work begins, helping avoid incompatible paths and reducing time-consuming reformulation cycles.

These specialists also apply targeted techniques to stabilize the API within the adhesive matrix. Their expertise encompasses performance-enhancing additives that enhance skin permeation, control drug crystallization, and improve transdermal or transmucosal wear—all without compromising safety.

2. Advanced Manufacturing Capabilities

The right partner will offer manufacturing technologies devised for adhesive drug delivery. These should include precision coating, solvent handling, and package converting systems that deliver uniformity and scalability.

Key manufacturing capabilities include:

  • Solvent coating technologies with controlled drying profiles to prevent API migration and ensure even distribution throughout the drug matrix.
  • Advanced lamination equipment that achieves bubble-free bonding between functional layers without affecting drug stability or release.
  • Precision package converting processes, such as rotary die-cutting and vision inspection, to ensure edge quality and overall product integrity.

A quality-focused partner will also use in-line monitoring systems to track critical quality attributes throughout production, not just at final release testing.

3. Regulatory Navigation Expertise

Adhesive systems present unique regulatory challenges. Partners with transdermal and transmucosal regulatory expertise understand how adhesive properties influence drug delivery and how to document those relationships effectively.

These experts stay up-to-date on evolving expectations for combination products, including specialized tests for skin adhesion, irritation, and sensitization. They develop comprehensive regulatory strategies that address both the pharmaceutical and device aspects of your product, helping you avoid delays.

Their experience also includes crafting robust validation protocols that demonstrate consistent manufacturing performance across different scales, as well as setting specifications that balance manufacturability with therapeutic performance.

Conclusion

Understanding the unique challenges of adhesive drug delivery systems is essential for successful product development. By partnering with specialists who bring formulation expertise, manufacturing capabilities, and regulatory knowledge, pharmaceutical companies can transform technical hurdles into opportunities for product differentiation.

ARx leverages decades of adhesive science expertise to help pharmaceutical partners navigate these development challenges. Our integrated approach provides a seamless pathway from concept to commercial product, turning complex delivery challenges into market-ready opportunities.

ARx is a patient-friendly, novel drug delivery partner. We specialize in oral thin film, buccal film, topical and transdermal patch strategies — all backed by tailored, full-scale development services. Contact us today to find the right delivery system for your API.