3 key factors for successful shell development
Far from being a mere packaging material, the capsule shell plays a critical role in ensuring the stability, performance, and shelf life of a soft capsule. Developing a robust and compatible capsule shell requires a comprehensive approach that considers the complex interplay between the shell components and the encapsulated fill.
This article highlights 3 key aspects of shell formulation development, from raw material selection to addressing common compatibility issues. A well-designed capsule shell is the key to unlocking the full potential of the encapsulated fill, ensuring that the product remains stable throughout its shelf life.
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Raw Materials Selection
The selection of appropriate gelatin types and plasticizers is the foundation of a successful shell formulation. Gelatin, derived from animal collagen, is available in various grades with different characteristics based on the manufacturing process. These characteristics, such as molecular weight distribution and amino acid composition, can significantly impact the processability and compatibility of the shell with the capsule fill. For instance, type A gelatins derived from pig skin typically display a broad molecular weight distribution, while type B bovine bone gelatin contains a high portion of alpha protein chains.
2. Broad Shell Formulation Screening on Capsules
Initial formulation screening should consider the drug substance's characteristics, the fill formulation properties, and potential interactions between the shell and the fill. Factors to consider include the drug substance's aqueous solubility, critical molecular structures or impurities that may induce crosslinking, the potential for migration of drug substance or fill components, and the impurity profile of the fill formulation excipients. Encapsulation trials are ideal for evaluating the compatibility and stability of different gelatin types and plasticizer combinations, as they can detect a variety of possible interactions and incompatibilities that may not be apparent in laboratory compatibility trials on raw materials. The prototypes should be assessed for critical quality attributes, such as rupture time, disintegration, water content, and capsule hardness, along with the remaining drug product CQAs.
3. Anticipating Common Compatibility Issues
Crosslinking, migration, and precipitation of the drug substance are common compatibility issues encountered in soft capsules.
Crosslinking, characterized by a decrease in dissolution and an increase in variability, can be addressed by optimizing the gelatin type, plasticizer type and amount, and to a lower extent, process settings. Factors that can positively impact crosslinking include the use of specific gelatin grades, plasticizer types and amounts, processing conditions and control of storage conditions.
Migration of components into the fill or into the shell, can often lead to physical instabilities and can be limited by adjusting the plasticizer type and amount.
In addition to these critical tests, the assay, identity, and degradation products must be determined, and the microbiological quality should meet the acceptance criteria for non-aqueous oral-use preparations. Depending on the specific characteristics of the drug substance and the formulation concept, additional tests may be necessary.
These tests should be defined based on the identification of the critical quality attributes of the drug product, following a Quality by Design (QbD) approach as outlined in ICH Q8.
Developing a robust and compatible capsule shell is a critical aspect of soft capsule formulation development. By adopting a systematic approach that considers the raw materials, formulation screening, and potential compatibility issues, formulators can develop soft capsule products that meet the desired quality attributes and ensure patient safety and efficacy. The capsule shell's impact on product stability and performance cannot be understated, and a thorough understanding of the complex interplay between the shell and the fill is essential for successful development.
Want to dive deeper into the intricacies of shell formulation development for soft capsules? Download our comprehensive e-book, "Shell Formulation Development for Soft Capsules," to gain expert insights for developing stable and compatible capsule shells.
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