In the fast-paced world of drug development, time is often the most precious commodity. For biotech companies working on oral solid dose (OSD) products, the pressure to move into the clinic quickly is immense. However, the current estimates for drugs to move from initial discovery to market is currently between 12 and 15 years. Investors want milestones, patients need solutions, and competitors are racing toward the same finish line. When 90% of drugs fail to reach phase 1 clinical trials, the early stage of drug development really matters.

So how do you accelerate early-stage development without sacrificing quality or compliance?

The Challenge of Speed in Early Development

When a molecule shows promise, the clock starts ticking. The first-in-human (FIH) trial is the gateway to proving safety and unlocking the next phase of funding. Yet, oral and nasal dosage forms present unique hurdles. Many new chemical entities are poorly soluble, unstable, or available only in gram-scale quantities. Regulatory require GMP compliance and robust documentation.

The challenge of drug developers is to create a formulation that is fit-for-purpose, robust enough for clinical use, but developed with speed and cost-efficiency in mind.

Selecting the right formulation strategy is crucial to speed in early development:

• Formulation Strategies for Class IIa:​
• Dissolution limited compounds. ​
• Enhancing dissolution primarily involves reducing particle size, thereby increasing the particle’s surface area. Therefore, micronisation /nano-milling to achieve particle size reduction is a typical way forward.

• Formulation Strategies for Class IIb:​
• Many of these compounds are crystalline.​
• Solubility enhancement is generally achieved by changing the form from crystalline to an amorphous form or by creating a new salt.​
  
• Formulation Strategies for Class III:​
• Permeation enhancers.​
• Typically, oil in water emulsions SEDDS/SMEEDS approaches are used to improve solubility​.

• Formulation Strategies for Class IV: ​
• These formulation strategies include micro/nano-emulsion suspension or solid amorphous dispersions.

Navigating Technical Complexities

Solubility is often the first major hurdle in drug development. Many new chemical entities fall into Biopharmaceutics Classification System (BCS) Class II or IV, which means they exhibit poor aqueous solubility and, in some cases, limited permeability across biological membranes. For oral dosage forms, these characteristics can significantly impact drug absorption, leading to unpredictable bioavailability and variable pharmacokinetics. This variability can complicate dose optimisation and therapeutic outcomes, making formulation strategies critical.

Stability is another critical concern in drug development. Active pharmaceutical ingredients (APIs) can degrade when exposed to heat, moisture, or oxygen, leading to reduced potency or altered safety profiles. Additionally, polymorphic changes in the solid-state structure can significantly impact dissolution rates and overall performance. Therefore, maintaining stability during storage, transportation, and handling is essential for early-stage formulation. This requires careful selection of excipients, packaging, and environmental controls to prevent degradation and ensure consistent quality throughout the product’s lifecycle. At early stage, developers also deal with the reality of limited API supply. At this stage, every milligram counts, so CDMO processes must minimise waste and maximise yield. At Upperton, we’ve developed our early development platform, UpperSolv^TM to use just 5g of API to screen up to 6 different formulation approaches.

Formulation Strategies for Rapid Progress

Speed means making smart choices and not cutting corners. For oral solid dose products, simplicity is the guiding principle. Capsules often take precedence over tablets because they require less processing and allow rapid dose adjustments. Powder-in-capsule (PIC) methods, where the API is filled directly into capsules, can eliminate multiple manufacturing steps and reduce timelines dramatically.

So, what does success look like?

It starts with a critical evaluation of API Physio-Chemical and Biological data. Solubility screening and prototype enabling formulation preparation can support with the early identification of challenges before investing heavily in development. This is particularly important as 40% of marketed drugs and nearly 90% of drug candidates exhibit poor water solubility. Therefore, early identification can help decision makers to plan their next steps around refinement early. Additionally, these types of phase-appropriate strategies keep development focused on clinical functionality rather than commercial perfection.
At Upperton, we use our UpperSolv^TM platform to identify and solve bioavailability challenges within 12 weeks.

Winning the Race to Clinic

By prioritising simplicity, leveraging enabling technologies, and working with partners who understand the nuances of early-stage development, biotech companies can accelerate their path to first-in-human trials without compromising quality or compliance. Whilst drug development is complex and expensive, biotechs know that time is the ultimate currency. Therefore, these strategies can make the difference between leading the race and falling behind.