Formulation as a Development Lever: Immediate-release and Controlled- release in Early-Stage Drug Development

In the fast-paced world of drug development, speed, clarity, and strategic decisions to move forward confidently are everything. As drug development teams navigate the critical preclinical and early clinical phases (Phase 1/2), the pressure to quickly generate reliable proof-of-concept (POC) data, understand safety margins, and demonstrate therapeutic potential is immense.

While discussions around immediate-release (IR) and controlled-release (CR) formulations are often reserved for commercial dosage forms, the principles behind these release strategies are profoundly strategic—especially in the earliest stages of development. Choosing the right in vitro and in vivo release profile at the start is not just a formulation decision; it is a strategic lever that can accelerate development and minimize risk.

Why Release Profiles Matter Early in Drug Development

At the earliest stages of development (preclinical and early clinical), formulation is not about patient convenience—it is about enabling the generation of critical data that informs whether and how a program moves forward. Strategic release profiles can:

• Enable toxicology studies with consistent, high-dose delivery.
• Generate reliable pharmacokinetic/pharmacodynamic (PK/PD) data in humans to understand exposure and effect.
• Demonstrate early POC data to justify further investment.
• Mitigate early challenges such as poor solubility, rapid clearance, or local toxicity.
• Accelerate timelines by enabling faster, more informative studies.

This is where IR and CR become powerful tools—not just dosage forms.

Immediate Release: The Fast Track to Critical Milestones

Immediate-release (IR) formulations are all about delivering the drug quickly and predictably into systemic circulation—perfect for when timeliness and clarity of data take priority.

Strategic Role in Early Development:

• Simple IR formulations like solutions, suspensions, or capsules can be rapidly developed, requiring minimal drug substance, making them ideal for first-in-human studies.
• High and predictable drug exposure from IR formulations supports effective dose-ranging and helps establish safety margins during toxicology studies.
• Immediate-release formats offer an unobstructed window into a molecule’s innate pharmacokinetic and ADME profile.
• When rapid therapeutic onset is needed and sustained exposure is not yet necessary, IR formulations pave a straightforward path to early proof-of-concept.

IR formulation strategies can involve the use of enabling technologies to improve bioavailability —even for poorly soluble drug substances such as spray-dried amorphous solid dispersions, lipid-based systems, or nanosuspensions.

Controlled Release (CR): Solving Problems, Unlocking Potential

The purpose of CR formulations is to modify the rate, duration, or site of drug release to meet specific therapeutic or developmental goals.

Strategic Role in Early Development:

• CR formulations help extend drug exposure for molecules with short half-lives by using simple, scalable prototypes like matrix mini-tablets or multiparticulates.
• By flattening pharmacokinetic curves, CR strategies can reduce peak concentration-related toxicity, allowing for safer administration of higher doses.
• Sustaining supersaturation or targeting specific regions of the gastrointestinal tract through CR can significantly enhance bioavailability.
• Early use of CR formulations enables differentiation by demonstrating potential clinical advantages such as reduced side effects or improved compliance.
• CR approaches can also minimize variability in pharmacokinetic data caused by differences in fed or fasted states, improving the reliability of early-stage studies.

Early-stage CR is not about complex commercial systems—it is about pragmatic, scalable solutions using right controlled-release polymers and technologies.

IR vs CR: It is Not Binary—It’s Strategic

The choice between IR and CR is not either/or. It is a programmatic decision based on your molecule’s properties and your development goals:

• Start with IR when speed, simplicity, and baseline PK data are priorities.
• Pivot to CR when early data reveal limitations—short half-life, toxicity, solubility issues, or therapeutic need for sustained exposure.
• Iterate Intelligently: Early IR data often inform the need for CR.

Partnering with CDMO for Success

In early development, your CDMO must be more than a manufacturer. They must be a strategic partner who understands:

• The urgency of rapid development with minimal API.
• The science of biopharmaceutics and formulation technologies.
• The clinical context of how formulation impacts data quality.
• The supply chain from tox batches to GMP clinical supplies—across both IR and CR.

Formulate Your Strategy with Purpose

In preclinical and early clinical development, release profiles are not just formulation attributes—they are strategic levers. The right release strategy can accelerate timelines, de-risk development, and unlock critical data faster.

Partner with Aragen that brings scientific depth, technological agility, and clinical supply expertise. We offer:

• Deep Pre-formulation & Materials Science Expertise : We specialize in characterizing compound properties critical for pharmacokinetic exposure, leveraging advanced materials science to guide formulation strategy from the outset.
• Clinical Formulation Development Excellence : Our team delivers phase-appropriate formulations—capsules, tablets, and enabling technologies—designed to meet clinical performance and regulatory expectations.
• End-to-End Clinical Manufacturing Capability : From toxicology batches to GMP clinical supply, our integrated infrastructure supports seamless scale-up and reliable production across development stages.
• Integrated Fast-Track Drug Development : We integrate drug substance and drug product activities into pre-built packages, enabling accelerated timelines, reduced hand-offs, and simplified CMC pathways.