EXTENDED RELEASE TABLET FORMULATION DEVELOPMENT
Developing a Once-Daily Bilayer Tablet for a 505(b)(2) Clinical Program
How Vici combined immediate- and extended-release APIs in one tablet—and delivered Phase 2 clinical supplies with amended-IND support in approximately six months.
This representative technical development story is based on pharmaceutical development work completed by Vici Health Sciences. Certain client, API, formulation, indication, dosage-strength, timeline, and regulatory details have been modified, generalized, or omitted to protect confidentiality.
Executive Summary
A sponsor pursuing a 505(b)(2) program needed a once-daily tablet containing two active pharmaceutical ingredients, or APIs. One API required immediate release, while the other required extended release. The program also included multiple active strengths and a placebo.
Vici Health Sciences selected a bilayer architecture so each API could use a separate formulation and process within one dosage form. The extended-release layer used a hydroxypropyl methylcellulose matrix, while a high-drug-load layer required granulation and additional tablet-fill capacity.
Vici developed and scaled the formulations, manufactured Phase 2 clinical supplies, and supported an amended IND in approximately six months. The development strategy also supported the sponsor’s formulation and broader intellectual-property objectives.
Project Snapshot
Client Profile
Confidential emerging pharmaceutical company
Development Pathway
505(b)(2)
Dosage Form
Once-daily bilayer oral tablet
Primary Challenge
Combining immediate- and extended-release APIs with different formulation and processing needs
Program Complexity
Multiple strengths, high-drug-load layer, placebo, scale-up, clinical supply, and amended-IND support
Vici's Scope
Formulation and process development, multi-strength strategy, scale-up, Phase 2 clinical supply manufacturing, and CMC support
Development Timeline
Approximately six months
Outcome
Multiple-strength bilayer product and placebo advanced into Phase 2 clinical supply manufacturing
The Development Challenge
The sponsor did not simply need two APIs compressed together. One layer had to release its API promptly, while the second had to control release over a longer period to support once-daily administration.
A bilayer tablet contains two separately formulated and compressed layers in one dosage form. This architecture allowed Vici to manage the APIs separately, but both layers still had to form one mechanically robust tablet with suitable layer adhesion, hardness, size, and handling performance.
The program also required multiple strengths, a placebo, a high-drug-load layer, practical commercial tooling, process scale-up, Phase 2 clinical supplies, and supporting CMC information for an amended IND—all under a compressed schedule.
Vici's Bilayer Formulation Strategy
For the extended-release layer, Vici used a hydrophilic matrix based on hydroxypropyl methylcellulose, or HPMC. As HPMC hydrates, it forms a gel-like matrix that helps regulate water penetration and drug diffusion.
The formulation development team blended a higher-viscosity HPMC grade with a medium-to-lower-viscosity grade. This combination provided additional control over matrix formation, release behavior, manufacturability, and adaptation across strengths; the polymer blend was one part of the overall release-control strategy.
The second layer contained a high percentage of API, leaving limited room for functional excipients. Vici used granulation to improve powder flow and bulk density so the high-mass layer could fill and compress more reliably.
Successful bilayer development required the layers to perform differently after administration while behaving as one tablet during compression, coating, packaging, and clinical use.
Multiple Strengths and Regulatory Strategy
Vici planned the strength family from the beginning. The team kept the qualitative composition similar, maintained dose proportionality where practical, and preserved the same basic release-control approach with minimal formulation changes.
This strategy reduced unnecessary differences among strengths and provided a practical basis for comparability, manufacturing, and regulatory justification. It was designed to support regulatory efficiency where acceptable to the agency; it did not guarantee a bioequivalence waiver or a particular FDA conclusion.
High-Drug-Load Manufacturing and Scale-Up
The high-load layer created powder-flow, density, and tablet-fill constraints. In addition to granulation, Vici used a deep-fill cam on the bilayer press, allowing greater powder-fill depth for the high-mass layer and the approximately 1-gram finished tablet.
Vici kept the tablet within standard B tooling, a widely used tablet-press format that broadened access to suitable manufacturing equipment and reduced dependence on specialized tooling. A nonfunctional appearance coating improved appearance and swallowability; it did not control drug release.
Accelerated Clinical Supply Execution
Vici integrated the two active layers, multiple strengths, a placebo, process scale-up, Phase 2 clinical supply manufacturing, and CMC support for an amended IND. Keeping these activities with one development partner reduced technical handoffs as the program moved from formulation into clinical manufacturing.
01
Formulation Architecture
02
Layer Development
03
Multiple Strengths & Placebo
04
Scale-Up
05
Phase 2 Clinical Supply
06
Amended-IND Support
The integrated program was completed in approximately six months. This timing reflected the specific circumstances of the project and should not be interpreted as a standard timeline for every bilayer development program.
Key Technical Decisions
Different Release Requirements
Separated the APIs into immediate- and extended-release layers.
Why it mattered: Matched each API with the formulation and process appropriate for its intended release behavior.
Extended-Release Control
Combined two HPMC viscosity ranges in a hydrophilic matrix.
Why it mattered: Added flexibility to tune matrix hydration, release behavior, manufacturability, and multiple strengths.
Multiple Strengths
Kept formulations similar and proportional where practical.
Why it mattered: Reduced unnecessary CMC and regulatory divergence among strengths.
High Drug Load
Used granulation to improve powder flow and density.
Why it mattered: Made filling and compression of the high-mass layer more practical.
Large Tablet Mass
Used a deep-fill cam while remaining within standard B tooling.
Why it mattered: Accommodated the required fill while preserving future manufacturing flexibility.
Patient Acceptability
Considered tablet geometry and applied a nonfunctional coating.
Why it mattered: Improved appearance and swallowability without relying on the coating for release control.
Compressed Clinical Timeline
Integrated development, scale-up, clinical manufacturing, and amended-IND support.
Why it mattered: Reduced handoffs and allowed the sponsor to advance the Phase 2 program efficiently.
Outcome
The program produced a bilayer formulation with the intended immediate- and extended-release architecture. Vici developed multiple strengths using a similar underlying strategy, prepared a placebo, and scaled the process for clinical manufacturing.
The approximately 1-gram tablet remained compatible with standard B tooling. Granulation and the deep-fill cam addressed the high-load layer’s filling requirements, while the HPMC matrix supported the extended-release design.
Vici manufactured Phase 2 clinical supplies and supported the amended IND within an approximately six-month integrated program. The work also supported the sponsor’s formulation and broader intellectual-property objectives. These outcomes do not imply commercial approval, process validation, or a specific clinical result.
Key Takeaways
- Bilayer tablets can manage APIs with different release and processing needs within one dosage form.
- Modified-release design must account for manufacturability and scale-up from the beginning.
- Multiple strengths should be planned before the first strength is finalized.
- High-drug-load layers may require process changes to achieve practical flow, density, and tablet fill.
- Integrating formulation, clinical supply manufacturing, and CMC support can reduce handoffs for emerging-pharma programs.
Planning a 505(b)(2) or Modified-Release Program?
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Vici Health Sciences | Technical Development Story