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How to overcome formulation challenges with liquid-fill capsules

How to overcome formulation challenges with liquid-fill capsules

Posted by Eli Elias on 14-Mar-2018 4:00:00 PM

Solid oral dosage forms remain the preferred route of administration for many reasons. Many drug candidates today, however, cannot be formulated as tablets due to their poor solubility, high potency or sensitivity to processing conditions. For these complex APIs, liquid-filled hard-shell capsules enable formulators to overcome these issues while also achieving improved efficacy and safety.

Complex molecules make for difficult oral solid dose formulations


Increasingly complex small-molecule APIs are presenting a new set of challenges to drug formulators. Approximately 40% of current market drugs and 80% of pipeline candidates meet the Biopharmaceutical Classification System (BCS) definition of poorly soluble (classes II and IV). In addition, the percentage of drug candidates that are classified as highly potent (highly potent active pharmaceutical ingredients, HPAPIs) is expanding. The global HPAPI market is expected to reach $34.8 billion by 2025, according to Grand View Research.

Deglobalization of APIs and Pharmaceutical Manufacturing


Liquid-fill capsules offer many benefits


For APIs that cannot be formulated as powders into traditional oral solid dosage forms — either due to toxicity concerns, issues with abrasiveness, hygroscopicity or sensitivity to degradation from light and heat — encapsulation of a liquid in hard-shell capsules is an attractive alternative that still allows formulation as an oral solid dosage drug.

Formulation as a liquid can overcome many troubling physicochemical properties for APIs, giving formulators much greater flexibility. In fact, liquid-fill capsules can provide drug manufacturers with the opportunity to create formulations not previously possible. Both the drug formulation and the polymer composition of the capsule can be customized to accommodate APIs with many different properties and desired dissolution profiles.

As importantly, the dissolution of liquid-filled capsules is generally superior to that of other oral solid dosage forms. For two-part hard capsules, dissolution can start in as little as five minutes and be completed within 15 — and is often more consistent when compared to other solid dosage forms. Hard-shell capsules can also be designed to dissolve under different pH conditions, allowing controlled drug delivery in the gastric fluids or intestine, for instance.

Furthermore, the use of lipid-based solutions as liquid carriers increases the bioavailability of liquid-filled capsules compared to solid oral dosage forms. Lipid carriers are readily metabolized and provide for optimized absorption of the API. It is also easier to achieve homogeneity across low- and high-potency API formulations.

E-book Liquid-Filled


Joining together


The connecting of two-piece hard-shell capsules containing liquid formulations is advantageous over forced sealing methods using sprays to fuse the two halves together. With the latter approach, it is possible to compromise the integrity of the shell, which may lead to leakage of the contents­ — something that is unacceptable for HPAPIs. In the banding process, on the other hand, the material used for banding is customized to work with the composition of the hard shell used to produce the two parts of the capsule. The band material seeps into the inseams of the capsule, drying and hardening at the same time, which allows for complete unibody fusion.


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Customizing and optimizing


At CapsCanada, we specialize in liquid-filled hard capsules (LFHCs). Over the last three decades, we have perfected the technology to optimize LQ-CAPS® Liquid Formulation Capsules for our customers. In addition to standard capsule compositions, we develop customized capsule solutions to address the formulation needs of highly complex APIs with the goal of optimizing their performance. We are continually innovating to develop proprietary polymer formulations that provide the most stable capsules and hold the greatest quantities of API possible.

These special capsule polymer formulations require custom banding solutions that ensure protection of highly potent and otherwise sensitive APIs. CapsCanada’s custom banding technologies create a custom seal, made with the raw material used to form the capsule (gelatin, HPMC, etc.), creating a secure seal that is both leak- and tamper-resistant.

Faster and more consistent dissolution inevitably improves the bioavailability of liquid-filled capsules, which provides enhanced efficacy overall. When combined with the greater security of hard-shell capsules, the result is better products that benefit manufacturers and patients alike.

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Topics: LQ-CAPS®