Challenges in Pre-Clinical Oral Drug Delivery
Pre-clinical studies are essential for evaluating the safety, pharmacokinetics, and efficacy of drug candidates before entering human trials. Rodents, particularly rats and mice, are widely used due to their genetic similarity to humans, cost-effectiveness, and well-characterized metabolic pathways [1]. However, oral drug delivery in rodents presents several challenges:
1. Gastrointestinal Sensitivity: Rodents have a highly acidic gastric environment. Many active pharmaceutical ingredients (APIs), especially acid-sensitive ones, degrade in the stomach or cause irritation, leading to reduced bioavailability and compromised safety profiles [2-3].
2. Capsule Size and Administration: Standard human capsule sizes are too large for rodents. Improper sizing can result in dosing inaccuracies, regurgitation, or injury during administration. This affects both animal welfare and data reliability [4].
3. Inconsistent Drug Release: Uncoated or poorly formulated capsules may disintegrate prematurely in the stomach, leading to variable pharmacokinetic profiles and reduced systemic exposure [5].
4. Formulation Scalability: Pre-clinical formulations often differ from clinical ones, complicating the transition to human trials. Regulatory guidance encourages consistency across development stages to improve translational success [1, 4].
Capsugel® PCcaps® – A Smart Solution for Pre-Clinical Trials
To address these challenges, Capsugel® PCcaps® gelatin capsules have been developed specifically for pre-clinical use in rodents. Backed by research and pharmaceutical engineering, Capsugel® PCcaps® offer a reliable, scalable, and animal-friendly solution.
Key Benefits of Capsugel® PCcaps®:
- Miniaturized Size (Size 9): With a volume of ~22 µL, these capsules are ideal for oral administration in small animals like rats [6].
- Solvent-Free Dosing: Enables administration of pure API without the need for solubilizing agents that may interfere with drug stability or animal physiology.
- Improved Animal Comfort: Capsugel® PCcaps® help prevent regurgitation and upper GI tract irritation, improving dosing compliance and reducing stress.
- Customizable Materials: Available in gelatin, Capsugel® PCcaps® can meet the need to match clinical formulations, supporting a seamless transition from pre-clinical to clinical phases [6].
Reaching the clinical trial stage is never easy. Capsugel® PCcaps® offer a practical and validated solution for oral administration in rodents, helping streamline pre-clinical development and improve translational success.
Enteric Functionality and Pre-Clinical Studies in Rodents – Introducing Capsugel® Enprotect® Size 9 Technology
For acid-sensitive APIs, Lonza Capsules and Health Ingredients has introduced the Capsugel® Enprotect® Size 9 capsule, a breakthrough in enteric delivery for rodent studies. This capsule integrates enteric protection directly into the capsule shell, eliminating the need for additional coating steps post-filling.
Advantages of Capsugel® Enprotect® Size 9 Capsules:
- Built-In Acid Protection: The capsule shell itself resists gastric acid, ensuring the API reaches the small intestine intact [7].
- Simplified Manufacturing: No need for external enteric coating, reducing complexity and cost in formulation development.
- Improved PK Profiles: Enables consistent release in the duodenum, enhancing absorption and reducing variability in pharmacokinetic data [7].
- Translational Consistency: Using the final dosage form in pre-clinical studies improves predictability for first-in-human trials and supports regulatory alignment.
Conclusion
Capsugel® PCcaps® and Capsugel® Enprotect® Size 9 offer practical and scalable solutions for oral drug administration in rodent models. Whether you're working with standard formulations or acid-sensitive APIs, PCcaps®, including the advanced Capsugel® Enprotect® Size 9 capsules, help overcome key challenges in pre-clinical research:
- Precise dosing in small animals
- Improved animal comfort and welfare
- Reliable pharmacokinetic profiles
- Seamless transition from pre-clinical to clinical development
- Simplified formulation with built-in enteric protection
By enabling early testing in the final dosage form, Capsugel® PCcaps® and Capsugel® Enprotect® Size 9 support more predictive and efficient drug development.
References
1. Shah SM, Jain AS, Kaushik R, et al. Preclinical Formulations: Insight, Strategies, and Practical Considerations. AAPS PharmSciTech. 2014;15(5):1307–1323.
2. Reix N, Guhmann P, Bietiger W, et al. Duodenum-specific drug delivery: In vivo assessment of a pharmaceutically developed enteric-coated capsule for a broad applicability in rat studies. Int J Pharm. 2012;422(2):338–340.
3. Directive 2010/63/EU of the European Parliament and of the Council on the protection of animals used for scientific purposes.
4. European Medicines Agency (EMA). Guideline on the conduct of pharmacokinetic studies in target animal species. EMA/CVMP/EWP/133/1999-Rev.1. 2023.
5. Nombret D, Robin S, Cade D. Enteric Coated Capsules Designed for Performing Pre-Clinical Trials. Poster presented at AAPS Annual Meeting. 2009.
6. Capsugel. PCcaps® to Speed up Pre-Clinical Trials. Technical Brochure. 1998.
7. Lonza. Lonza Launches Enprotect® Size 9 Capsule to Accelerate Pre-Clinical Development of Acid-Sensitive Active Pharmaceutical Ingredients. Press Release. June 2024.