Five hidden risks in early-phase OSD formulation development
Early-phase oral solid dose (OSD) development is inherently complex, and formulation decisions made at this stage can have far-reaching effects. Choices that may seem sufficient to achieve a functional product for first-in-human studies can derail a program later when scalability, stability, or regulatory scrutiny come into play.
Understanding where hidden risks tend to arise can help teams avoid preventable delays, reduce rework, and maintain momentum through development.
Approximately 40% of marketed drugs and nearly 90% of drug candidates in development exhibit poor water solubility, which can compromise bioavailability and therapeutic efficacy (Acta pharmaceutica Sinica. B, 5(5), 442–453).
Here are five areas where early decisions can introduce long-term risk, along with practical ways to plan more effectively from the start.
1. Overlooking API complexity
The risk:
Unstable, poorly soluble, or variable APIs can quietly compromise formulation efforts. Today, a significant portion of pipeline compounds—by some estimates, up to 90%—face solubility or bioavailability challenges. Without early insight into the physicochemical behavior of the API, developers risk selecting suboptimal excipients or delivery strategies that underperform or fail to scale.
The opportunity:
Technologies that characterize and predict API behavior—such as accelerated stability modeling, in silico screening, and machine learning-guided formulation tools—can help identify strategies to improve solubility and bioavailability. Rather than predicting solubility itself, these technologies help guide smarter formulation choices, conserving valuable API and reducing trial-and-error in the lab.
2. Choosing the wrong dosage form
The risk:
The choice of dosage form can shape the entire development path. While it’s often driven by clinical considerations in early-phase development, failing to account for long-term needs, such as patient population, market access, or intended route of administration, can require reformulation or bridging studies later.
The opportunity:
Grounding formulation strategy in a clearly defined target product profile (TPP) helps teams weigh near-term feasibility against long-term viability. In silico tools can further aid in evaluating formulation approaches based on both API characteristics and intended pharmacokinetics, and manufacturing technologies.
3. Formulating without scalability in mind
The risk:
A formulation that performs well in a small-batch lab setting may hit friction when scaled to clinical or commercial production. Excipient choices, manufacturing complexity, and equipment constraints can all become limiting factors, especially with high-potency or poorly soluble APIs.
The opportunity:
Formulation teams should evaluate manufacturability early, considering not just yield and throughput, but also technical transfer risks and process reproducibility. Technologies like spray drying, hot melt extrusion, or lipid-based formulations can improve bioavailability, but require careful scale-up planning from the start.
An estimated 40% to 50% of clinical development failures are linked to a lack of efficacy, often associated with formulation issues such as poor stability or inadequate drug-excipient compatibility (Acta pharmaceutica Sinica. B, 12(7), 3049–3062).
4. Underestimating regulatory and stability factors
The risk:
Early formulation decisions directly affect the quality and completeness of CMC data submitted in IND filings. Choosing excipients without considering their regulatory status or failing to anticipate how a formulation will hold up under ICH stability conditions, can delay development or trigger reformulation midstream.
The opportunity:
Tools like accelerated stability modeling, guided by data-driven algorithms, can help forecast shelf life and storage requirements—reducing guesswork and giving regulatory teams greater confidence in early submissions.
5. Siloed thinking and short-term decisions
The risk:
Even well-designed formulations can run into trouble when developed in isolation. Choices around dose strength, packaging format, or excipient use may seem minor, but they can conflict with clinical packaging, supply chain constraints, or commercial production goals.
The opportunity:
Cross-functional input during early formulation helps ensure alignment across analytical, regulatory, clinical, and manufacturing stakeholders. Predictive modeling platforms that simulate compaction behavior, stability, or pharmacokinetics can support more integrated planning by providing clearer visibility across development touchpoints.
Building stronger foundations for development
Early formulation is more than a technical milestone. It’s a strategic inflection point. Teams that approach it with a broader lens can reduce risk, conserve resources, and build a clearer path to market.
Incorporating digital modeling, platform technologies, and cross-functional insight from the outset creates a more resilient formulation strategy that supports both the science and the long-term success of the program.
Explore how our OSD solutions support smarter formulation decisions at every stage.
