Novel excipients: the key to unlocking drug innovation
pharmafile | October 6, 2025 | Feature | Business Services | Lubrizol, Pharmacy
ADVERTORIAL, IN ASSOCIATION WITH LUBRIZOL
Meera Raghuram, Director of Regulatory and Sustainability Strategy at Lubrizol, explores how formulators can overcome the barriers they face in using novel excipients to bring difficult-to-deliver drugs to market
Formulation challenges are increasing as drug molecules become ever more complex, with growing numbers of poorly soluble, poorly bioavailable active pharmaceutical ingredients (APIs) in the development pipeline. The need for novel excipients to unlock the potential of these BCS Class II and IV brick-dust APIs has never been more urgent.
Despite this, innovation in excipient technologies has not kept pace. Many common excipients are decades old and may not offer the best solution for optimising difficult-to-deliver APIs. Yet developers remain cautious about embracing new excipients due to ambiguity in their regulatory approval process. This creates an innovation-stifling catch-22, in which formulators are hesitant to use novel excipients and manufacturers are hesitant to invest in developing them.
The approval paradox
The definition of ‘novel excipient’ covers a wide range of meanings. It may be a true new chemical entity (NCE), such as Lubrizol’s Apinovex™ and Apisolex™ polymers, which are designed to meet the specific formulation challenges of brick-dust APIs. It may be a modified existing excipient, or one repurposed from a related industry such as food or cosmetics. In many cases, an excipient may be considered novel simply if used in a new route of administration.
However, regulatory ambiguity continues to deter their widespread adoption. Unlike APIs, excipients are rarely assessed independently, but only within the context of a drug product submission package. This places the regulatory risk squarely on the drug developer, so even if better options exist, many formulators prefer to use excipients with precedence of use in an approved drug. In the US, this means excipients listed in the US Food and Drug Administration’s (FDA) Inactive Ingredient Database (IID). In Europe, there is no central IID equivalent, although the European Medicines Agency (EMA) requires safety data tailored to the intended route of administration. In Asia-Pacific regions such as Japan and China, regulatory expectations can differ again, further complicating global drug-development strategies.
The absence of a harmonised, independent approval pathway for excipients contributes to a cautious mindset across the entire pharmaceutical industry. Ultimately, this slows progress in bringing innovative formulations to market.
The benefits of using novel excipients
The need for new excipient technologies is undeniable, particularly given the growth in complex molecules and advanced drug modalities with formulation needs that cannot be met by many ‘traditional’ excipients. Novel excipients offer a number of significant advantages.
1. Enhanced solubility and bioavailability: Poor aqueous solubility affects up to 90% of new chemical entities and over 40% of reformulated products.1 This hinders dissolution, absorption and pharmacokinetics, and results in poor bioavailability.1 Lubrizol’s Apisolex™ polymer can enhance solubility in parenteral and injectable dose forms by up to 50,000-fold and offer high drug loading of up to 40:100 APR to solubilizer.
2. Leaner manufacturing: Novel excipients can support simpler, more efficient production processes. Apisolex™, for example, enables straightforward formulation methods like solution mixing and emulsion formation, while maintaining high API recovery rates of over 90%.
3. Patient-centric formulations: Regulatory bodies increasingly emphasise the importance of an optimised patient experience. Lubrizol’s Carbopol® polymer excipient has taste-masking properties and excellent mucoadhesion to improve palatability. Its high drug-loading capacity allows for smaller, easier-to-swallow dosage forms that can increase compliance in paediatric and geriatric populations.
4. Enabling drug repurposing and lifecycle management: Novel excipients can facilitate reformulation of existing APIs, allowing developers to extend the life cycle of established drugs or pursue accelerated approval pathways such as the US FDA’s 505(b)(2). They can also give a degree of IP protection not offered by existing excipients.
Case study: Apinovex™ – a solubility-enhancing novel excipient for brick-dust APIs
Poorly soluble BCS Class II and IV brick-dust APIs remain among the most stubborn formulation challenges. Lubrizol’s Apinovex™ polymer enhances solubility to allow more efficient oral dosage forms with high, stable drug loading. Winner of the CPhI China 2025 Pharma Excipient Award, this high molecular weight, novel polymer excipient stabilises spray-dried amorphous solid dispersions, even after six months under accelerated conditions.
Apinovex™ is non-mutagenic, soluble in water and common pharmaceutical solvents, and is compatible with a wide variety of APIs. It produces low-viscosity solutions for ease of processing and has similar chemistry to our existing, widely-used Carbopol® polymers. This versatility enables new drug development and reformulation of existing products via the FDA’s 505(b)(2) pathway, with the benefit of IP protection.
In case studies with BCS Class II itraconazole and ritonavir, Apinovex™ offers up to a ten-fold improvement in crystalline API dissolution. It also allows high (up to 80%) drug loading via spray-drying – twice that of Soluplus® and AFFINISOL™ HPMC excipients. This enables smaller, more patient-centric dosage forms, such as a single tablet delivering multiple APIs, and opens the door to innovative administration possibilities, including custom-release profiles.
Collaboration as an innovation catalyst
Bringing a new drug to market is a costly business – estimated at over $879 million in the US alone.2 In such a high-stakes environment, pharmaceutical companies need strategies to de-risk their adoption of novel excipients.
At Lubrizol, we believe early and active collaboration with excipient suppliers is the key to building formulator confidence in novel excipients. This enables identification of the developer’s specific unmet needs, for which the supplier may have solutions to help. For example, including the excipient in a drug product’s non-clinical animal toxicity studies can streamline and accelerate development timelines by identifying safety concerns and data gaps early in the process. We actively support this model by working with partners to co-develop data and regulatory submissions. To help streamline the approval process, our Drug Master Files (DMFs) are used in the US, China and Canada. Data-sharing agreements are an alternative in regions where DMFs are not used, such as Europe.
Bridging arguments can mitigate regulatory risk. If a novel excipient is chemically similar to an approved counterpart, existing safety data may support the new application. For example, some older grades of Lubrizol’s Carbopol® polymer excipients were manufactured using benzene, which is no longer a preferred solvent. Newer grades utilise acceptable solvents such as ethyl acetate. For manufacturers wishing to switch to a benzene-free grade, we can provide data showing the physical and chemical properties of the legacy and new grades – including the safety – are comparable.
Unlocking the future of formulation with novel excipients
New drug modalities require new formulation tools – and that includes novel excipients. At this critical point, to realise the promise of this exciting new age of therapeutic discovery, it is essential that:
- Formulators see novel excipients as enablers, not risks
- Collaboration starts early to address unmet formulation needs and develop new solutions
- Bridging strategies and collaborative data generation are used as de-risking strategies
- Both excipient suppliers and drug developers lobby for regulatory clarity.
Without action, many high-potential APIs may never get beyond the laboratory walls, denying patients what could be life-changing medicines. By collaborating, the pharmaceutical industry can unlock the potential of transformative therapeutics and deliver them to market more efficiently and cost-effectively.
References:
- Kalepu, Nekkanti. Insoluble drug delivery strategies: review of recent advances and business prospects. Acta Pharm Sin B, 2015;5(5):442-435. doi: 10.1016/j.apsb.2015.07.003
- Sertkaya et al. Costs of drug development and research and development intensity in the US, 2000-2018. JAMA Netw Open, 2024;7(6):e2415445. doi:10.1001/jamanetworkopen.2024.15445
Meera Raghuram, Director of Regulatory and Sustainability Strategy at Lubrizol
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