Developing fixed dose combinations using capsules

With few potential blockbuster drugs in the pharma pipeline right now and the shrinking drug pipeline, many pharmaceutical companies are looking to expand their product portfolio from their existing molecules. The most common strategy is to expand into fixed-dose combination-based products which involves combining two or more existing molecules, in a single formulation. This can offer several advantages, such as, providing a synergistic therapeutic effect, a better safety profile with fewer side effects, or a better release profile. Some of these combinations can offer multiple release profiles (where one drug may be intended for immediate release and the other for modified release or each of the constituent drug may be designed for release at different locations within the gastrointestinal tract.) Combination products may also help increase patient adherence by reducing pill burden. 

Hard capsules in fixed-dose combinations

Developed in the 19th century, two-piece hard capsule has been a popular dosage form in the pharmaceutical industry and is a suitable dosage form for delivering fixed-dose combinations (FDC) formulations. It is available in many sizes: standard hard capsules typically range as big as size 000 to as tiny as size 5 and can accommodate various fill volumes. To encapsulate additional fill volumes outside traditional sizes, some intermediate sizes called “elongated sizes” also exist. These typically have an extra 10% fill volume over the standard sizes to handle variations in density. Customised sizes can also be developed by capsule manufacturers if a specific formulation or delivery technology calls for such engineering. The advent of hypromellose (HPMC) capsules also makes it easy now to fill in hygroscopic/moisture-sensitive ingredients, which has been a challenge with traditional gelatine capsules. 

 

Encapsulation of liquid combination 

Combination capsule products have naturally evolved as a result of advancement in capsule filling technology. Beyond powder filling, today formulation scientists can achieve combination liquid filling in capsules. It is possible to mix beads and pellets with a liquid or insert small liquid filled capsules into larger liquid-filled capsules.  

Technology and increased understanding of self-emulsifying drug delivery systems coupled with advances in commercial filling equipment have reduced formulation difficulties. As a result, developing and commercialising combination products is easier than ever and can benefit both patient and manufacturer.  

 

Encapsulation of combinations for inhalation 

Hard capsules can be used for inhalation delivery of drugs, where the capsule is punctured and the patient inhales to facilitate the powder reaching the lungs. In capsuled-based dry powder inhalation technology, the use of a combination therapy usually yields better results than using a single ingredient. A good example is the mixture formoterol-budesonide. The single capsule combination of formoterol-budesonide appears to be more efficacious and safer than budesonide alone for the treatment of asthma

As the use of pulmonary drug delivery as a non-invasive route for treating systemic diseases has garnered interest in recent times, combination inhalation therapy using a simple delivery system such as capsule-based DPI products can be considered a suitable option. 

 

Conclusion

FDCs provide ample opportunities to innovate oral solid dosage forms and capsules can offer new drug delivery solutions by housing different product forms besides powders, such as pellets, minitablets, capsules, liquids, and semi-solids. With the advancement in encapsulation technology, combination filling in capsules has got simpler.  

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