Capsugel uses an array of specialized taste masking technologies and formulation approaches to address the bitter taste of many APIs in oral dosage forms. The quest for more effective taste masking approaches has attracted significant industry interest due to the compelling effect it has on patient compliance, particularly among pediatric and geriatric patients. The remaining challenge is meeting a number of product specifications in a narrow formulation space.
Capsugel is uniquely differentiated in having industry-leading expertise in innovative taste masking approaches and enabling technologies that are used to create optimal solutions for our customers’ drug delivery needs. A full range of specialized capsule technologies complements this formulation capability, providing additional taste masking and dosing functionality / flexibility (e.g. sprinkle-capsules).
Taste masking Strategies
Taste masking is typically accomplished in one of three ways:
- Using sweeteners, flavors, and viscosity modifiers to manipulate the perception of taste without changing the concentration of free (i.e. unbound) drug in solution.
- Preferentially binding the drug to a substrate that reduces the free-drug concentration, ideally below the taste threshold.
- Applying functional coatings that modify the release of the drug, keeping the free-drug concentration below the taste threshold for a time period relevant to the preparation and administration of the dose.
Capsugel uses all three of these approaches depending on the application, but the third methodis often the most effective in our experience. During formulation, a risk-based approach is used to select the necessary excipients, evaluating market-accepted materials with established safety data at levels that achieve the desired dosage form performance and stability. The initial quality control metrics are:
- The amount of active released over an appropriate time in a volume of the main excipient that is relevant to preparation and administration of the product.
- The amount of active released over an appropriate time in the main excipient that is relevant to the time the product is in the mouth.
Armed with the initial characterization data and the target product profile, the optimal taste masking strategy and dosage form are selected. Multiple approaches (e.g. lipid multiparticulates with functional coatings) may be required. The ultimate goal is to select a formulation that is stable, ideally preservative-free, and amenable to flexible, uniform dosing for a broad range of patient populations.
Taste masking with Coatings
Capsugel uses a wide range of taste masking and modified release coating technologies, with definition of the optimal approach based on specific API characteristics and the target product profile:
- pH-triggered (enteric, reverse enteric)
- Time release (bursting)
- Lipid based (LMPs)
The key to a successful formulation design is a rational technology and dosage form selection process. The perception of taste is dependent on multiple factors, including texture or mouth-feel, odor, taste and after-taste. We evaluate the need for taste masking as a first step. For example, we have found that multiparticulates below 250 microns in diameter typically have good mouth-feel for patients and can therefore facilitate good taste experience. Ideally, taste issues are identified early in clinical development using sensory information that helps determine the compliance risk for patient populations. A thorough characterization of the active ingredients is conducted in an initial screening process.
Capsugel works closely with our customer to identify key components of the target product profile, addressing such issues as:
- Equivalent performance compared to previous formulations
- The use of suitable, safe excipients that are accepted by the market
- The ideal release profile for the target patient population
Armed with this information, Capsugel works with the customer to select the most promising approaches to investigate and develop.
In our experience, we have found that the combination of multiparticulate formulations, functional coatings, and – in many cases – functional capsules serves as a powerful toolbox for meeting target product profiles. This includes taste masking of bitter compounds – especially for specialized patient populations.