The engineering of combination products has evolved into a systems-level challenge, where the success of drug delivery depends equally on molecular compatibility, device integrity, and material behavior under physiological stress. Materials science in particular has become a critical determinant in whether such products can simultaneously satisfy therapeutic, safety, and regulatory performance thresholds.
In addressing the complex demands of drug-device integration, medical-grade thermoplastic polyurethanes (TPUs) provide a rare trifecta of tunable mechanics, chemical inertness and proven biocompatibility. While this polymer class is historically underutilized in drug delivery compared to more common materials like ethylene-vinyl acetate (EVA), it is increasingly favored in specialty product design for both extended release and implantable combination devices.
Material Selection in Combination Therapies
According to FDA definitions, a combination product integrates two or more regulated components (typically a drug and a device) into a single therapeutic system (e.g., intravaginal rings, drug-coated stents, long-acting injectables, wearable insulin pumps). In these systems, the material is not simply structural but is often the medium through which the drug is stored, released, and delivered to the target tissue.
This introduces multiple performance variables that must be tightly controlled, including: elution rate, modulating how a drug diffuses from the matrix; loading capacity, being the extent to which the material can incorporate and retain an active pharmaceutical ingredient (API); stability in terms of resistance to degradation by solvents, bodily fluids, and sterilization processes; nonreactivity with tissue and the immune system, including resistance to fibrous encapsulation; as well as versatile processability across manufacturing methods such as injection molding, extrusion, or solvent casting.
Modern TPU formulations are being designed to bridge the gap between pharmaceutical performance needs and device manufacturability. The polymer’s architecture can be precisely engineered by modifying polyol type, segment distribution, and crystallinity, meaning multivariable controllable performance across mechanical, swelling, and pharmacological dimensions.
Some see materials as passive. But TPUs, in particular, present an open lane for fine-tuning mechanics, permeability, and drug handling. Tailor the chemistry to the application and the regulation, and TPU turns into a precision tool for shaping both function and compliance compatibility.
Fluid interactions and controlled swelling sit at the heart of in-body compliance, and with TPU, this interplay can be tuned to deliver both reliable placement and patient comfort for devices that live in the body for weeks or months, like hormonal implants or intravaginal rings.
Ultimately, a data-driven approach allows material selection to inform comfort and compatibility alongside longterm clinical reliability. Developers stress-test TPU key variables like water absorption, contact angle, and dimensional change in preclinical screenings to determine whether a material is viable for their specific drug, biologic, or other payload as well as extended in vivo use.
Avoiding Material–Drug Compatibility Failures
Material–drug mismatches are a common driver of redesigns in combination product programs and often emerge during scale-up or accelerated stability testing, rather than initial formulation. Because the performance of TPU in drug-device systems is highly formulation-dependent, early dialogue between developers and materials specialists helps avoid problems related to release profile, stability and manufacturability. Among the most common challenges:
The vehicle used to solubilize a drug can compromise material integrity if improperly matched.
Material–drug interactions that promote API absorption rather than diffusion can lead to batch variability and failure to meet dosing specifications.
Hydrolytic or oxidative degradation, along with solvent-induced swelling, can lead to premature failure or loss of dosing control.
To address these challenges, solvent resistance and chemical compatibility testing should be incorporated early in the material selection process, especially in systems where the material acts as a drug reservoir or diffusion barrier. These evaluations help determine how a polymer interacts with various solvents, excipients and APIs, and include screening for absorption, plasticization, and hydrolytic degradation.
For hot-melt extrusion and similar processes, cryogenic milling provides the fine polymer powders needed to support uniform drug distribution and predictable elution profiles. The ultra-low temperatures used in cryomilling prevent unwanted thermal transitions or oxidation, helping to retain polymer performance while achieving a particle size range necessary for formulation uniformity.
Cryomilling can be deceptively complex, however, because it’s not just about grinding a material down, but also about preserving molecular weight, preventing oxidation, and keeping the polymer completely dry throughout the process. TPU and similar polymers are highly susceptible to moisture uptake during milling and handling, and humidity control is essential to preventing molecular degradation that can affect the performance of the formulation.
Because of this, developers are advised to vet downstream partners carefully for both cryogenic milling expertise and proper environmental controls, particularly when working with high-value or moisture-sensitive polymers.
Design Trade-Offs
Designing for comfort and compliance often favors reduced device thickness, but doing so can affect structural robustness, limit drug payload, shorten delivery duration, and generally place increased demands on the material’s performance. Likewise, enhancing permeability may accelerate elution but reduce shelf-life or in vivo stability.
While TPU can be tuned to meet a wide range of performance targets, these parameters often influence one another and must be managed in concert. Empirical studies and simulation tools are routinely used in parallel to optimize drug-delivery release characteristics, accounting for differences in polymer architecture, drug content, and dimensional constraints. Here again, findings from early screening and prototyping help to refine both the selection of the base polymer and the downstream manufacturing approach.
Navigating Regulatory Requirements
For combination products, regulatory approval requires alignment with both medical device and pharmaceutical standards, adding layers of complexity to the submission process. On the device side, materials must demonstrate compliance with ISO 10993 biocompatibility standards, which assess cytotoxicity, sensitization, irritation, systemic toxicity, and potential for long-term implantation.
Simultaneously, materials used in the drug-contacting components of combination products are expected to conform to pharmaceutical-grade manufacturing standards, including Good Manufacturing Practice (GMP) requirements for consistency, purity, and traceability. Whether part of a drug or biologic filing, the Chemistry, Manufacturing and Controls (CMC) portion of the New Drug Application (NDA) or Biologic License Application (BLA) provides critical information about how the product is formulated, manufactured, and controlled to GMP standards. If the polymer also plays a direct role in drug delivery, it is often backed by a Type III Drug Master File (DMF) submission to the FDA.
From ISO 10993 to GMP and DMF support, assembling a complete, integrated materials dossier can shorten timelines and eliminate friction across quality and regulatory teams. Due diligence matters: developers should prioritize suppliers with a clear track record in combination products and ready access to compliance documentation.
Materials as Strategic Enablers
Programs that succeed in both performance and regulatory alignment typically bring materials expertise into the conversation early. This makes it possible to align drug properties with polymer behavior before design lock, using precedent data to anticipate release profiles and stability.
When teams wait too long to think about materials, they often run into problems that force them to go back and redesign. Sometimes that means repeating tests, requalifying components, or even starting over. But when specialists are involved early, they can help guide decisions that lead the project to faster prototyping and smoother iteration.
Because they merge pharmacologic and mechanical functions, combination products demand a level of engineering precision that encompasses both therapeutic outcome and delivery integrity, and material selection is central to this mission.
Strategic integration of TPU at the design stage allows developers to extend material performance across diverse therapeutic formats including implantables, injectables, and transdermals. For developers seeking to stand out in crowded markets, TPU’s capacity to support precision drug delivery while maintaining structural and biological performance can be a differentiator.
This article was written by Nathan Rohner, PhD, Scientist at Lubrizol, Wickliffe, OH, where he leads polymer innovation for pharmaceutical and medical device applications. For more information, visit here .
