Click to Read：Formulation Changes and Bridging During Formulation Development – Part 1
ABSTRACT: The second article in the series focuses on real life examples of bridging studies due to formulation changes from Phase 1 clinical study to commercialization of drug and finally real-life examples of bridging studies due to reformulation (formulation changes) post commercialization of drug
Real life examples of Bridging studies due to formulation changes from Phase 1 clinical study to commercialization of drug
The six real-life examples below illustrate the use of bridging studies due to formulation changes during drug development. These cases illustrate how the companies navigated formulation changes and conducted bridging studies to demonstrate equivalence between early-phase and final commercial formulations.
1. Abilify Maintena® (Aripiprazole)
Drug Background: Abilify Maintena® is a long-acting injectable form of aripiprazole, used for schizophrenia and bipolar disorder.
Formulation Change: The transition from oral tablets to a long-acting injectable formulation required substantial changes to the drug’s formulation to enable a controlled, steady release over an extended period.
Bridging Studies: Bridging studies were conducted to confirm that the extended-release injectable form produced plasma concentrations comparable to the daily oral doses in terms of safety, efficacy, and therapeutic outcome. Pharmacokinetic and pharmacodynamic studies confirmed bioequivalence, and clinical bridging studies ensured the new formulation met therapeutic goals over time.
Result: The bridging studies successfully demonstrated therapeutic equivalence, allowing the injectable form to reach the market as a suitable long-term alternative to the daily oral regimen.
2. Nexium® (Esomeprazole Magnesium)
Drug Background: Nexium® is a proton pump inhibitor used for acid-related disorders. Initially developed as a delayed-release capsule, formulation changes were introduced to improve patient convenience and adapt to various patient needs.
Formulation Change: To accommodate different patient populations (e.g., those who cannot swallow capsules), new formulations such as oral suspension and tablets were developed. The tablet formulation required a change in excipients and coating materials.
Bridging Studies: Pharmacokinetic studies were conducted to confirm that the new tablet and oral suspension formulations were bioequivalent to the original delayed-release capsules. Dissolution studies also ensured the delayed-release characteristics were consistent across formulations.
Result: The bridging studies confirmed bioequivalence, allowing the new formulations to be marketed alongside the original. This increased accessibility for patients requiring alternative forms.
3. Concerta® (Methylphenidate)
Drug Background: Concerta® is an extended-release form of methylphenidate used to treat ADHD. The drug uses an osmotic-release oral system (OROS) to provide a controlled release of methylphenidate throughout the day.
Formulation Change: In developing the final OROS form for commercialization, adjustments were made to optimize the drug release profile, improve manufacturing consistency, and scale up production.
Bridging Studies: Pharmacokinetic studies were essential to confirm that the final commercial OROS formulation provided similar release rates and therapeutic plasma concentrations as seen in earlier formulations. These studies compared parameters like Cmax and AUC to ensure cons...
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