Looking into Liquids

October 16, 2007

5 Min Read
Looking into Liquids


Consumers are taking increased individual responsibility for managing their health, according to a new Datamonitor report.1 This global mega trend toward a more self-responsible consumer is something formulators see on a daily basis. Company research shows savvy consumers want products that maintain the strength of the medication or ingredient, are easy to swallow and effectively mask unpleasant taste and odor.2 In addition, more than a quarter of consumers want supplements derived from vegetarian or plant-based sources, and that percentage continues to grow.3

But, beyond that, shoppers are seeking products they are confident will work. It is not enough to deliver the supplement attractively. Once it is swallowed, consumers want to believe it dissolves. The term bioavailability—the rate and extent to which a product is absorbed into the body—has been a key factor in the pharmaceutical industry for years, and is now showing up on dietary supplement bottles.4

One innovative technology developed to help improve bioavailability and the absorption of active ingredients is liquid-filled capsules. A predissolved active ingredient works more quickly, because the body doesn’t have to spend time dissolving the solid material; essentially, the product is ready to be absorbed upon ingestion. Because capsules are readily available in plant-based HPMC, the vegetarian solution is an easy choice.

Liquid Formulation Strategies

Liquid formulation strategies based on pharmaceutical drug development protocols have benefited the dietary supplement industry. Excipient suppliers now provide a host of liquid and semisolid excipients to help solubilize compounds for improved delivery. The major techniques used to enhance bioavailability are self-emulsifying delivery systems.5,6,7 These systems are oily, preconcentrated solutions of the active ingredient and excipients that help keep the active dissolved. In the gut, these systems spontaneously form oil-water emulsions, making it easier for them to be absorbed by the body.

Liquid strategies have also been used for compounds where only a small amount of the active ingredient is needed. In a true solution form, the active ingredient is uniformly dispersed throughout the formulation, ensuring the customer gets a uniform dose from the liquid.8 Pharmaceutical companies use liquids for low melting point compounds to avoid high excipient loads typically required to reliably process such active ingredients.

Formulators go through a customary process to evaluate whether the active ingredient is a good candidate and if suitable excipients are available. Keep in mind that neither the active nor the excipient should cause the gelatin shell to gain or lose excessive moisture. All substances must be chemically compatible or cross-linking might occur. In such cases, an HPMC capsule might be the better choice.

Hard Capsules vs. Softgels

There is a difference between the types of liquids filled into hard capsules—either gelatin or HPMC—and in soft gelatin capsules. Sometimes the formulation will dictate the capsule type; but, in cases where the formulation allows a choice between dosage forms, hard capsules have some advantages because they are less complex to manufacture.

First, soft gelatin contains a significant amount of plasticizer, usually glycerol or sorbitol. Plasticizers impart elasticity to the gelatin shell and allow it to accommodate a wider range of hydrophilic excipients; but, their presence raises the issue of component migration. For example, if the plasticizer solubilizes the compounds of the formulation, those compounds can migrate into the soft gelatin shell and might not release successfully in the body. Conversely, the plasticizer might migrate into the formulation, leaving the possibility of broken shells due to brittleness.

Furthermore, the soft gelatin might expose the active ingredient to more oxygen than a hard capsule would, because the plasticizers in the soft gelatin create larger air channels. Greater exposure to air increases the potential for oxidizing, or degrading, the fill material. In addition, hard gelatin capsules can be filled in a nitrogen environment to further protect the contents. The smaller channels of hard gelatin capsules also mask the off-tastes and odors associated with fish oils and other lipids used to suspend formulas better than softgels can.

Manufacturing softgels is vastly different from filling hard gelatin capsules with liquids. First, empty hard gelatin capsules are purchased separately and then filled. With softgels, two ribbons of gelatin come together in a die to form the capsule, which is filled and sealed in one continuous process. The softgel process can neither accept fill materials that exceed 35°C nor formulations containing large particles or fibrous materials that might prevent a secure seal when the two sides of the shell come together.

One final visible difference between liquid-filled capsules and softgels is the perception of what is on the inside. In a national poll conducted by the Natural Marketing Institute (NMI), customers indicated they preferred liquid-filled capsules over softgels.9 According to NMI, consumers may not realize softgels can contain a liquid—they think it is a solid gel-like product.

Recent campaigns by a major OTC marketer have been designed to drive the point home that there is liquid on the inside—something liquid filled-capsules can more easily, and visibly, demonstrate. 

Missy Lowery is the marketing manager and Matt Richardson, Ph.D., is business development manager for Capsugel, a world leader in dosage form development and capsule manufacturing for the nutraceutical, pharmaceutical and OTC markets. Capsugel (www.Capsugel.com) has 10 global manufacturing facilities and produces Licaps® liquid-filled capsules, Vcaps® vegetarian Capsules and capsule filling and sealing equipment among many other products. Capsugel is exhibiting at SupplySide West, Booth #16018.


1. New Developments in Global Consumer Trends, Datamonitor, April 2007.

2. Lowery M. “National quantitative consumer study of dosage forms – linking form with preference to improve compliance.” Poster presentation, American Association of Pharmaceutical Scientists, 2005.

3. Consumer Insight & Strategy, The Natural Marketing Institute Health & Wellness Trends Database, April 2007.

4. Joshi & Shah. “Review of lipids in pharmaceutical drug delivery systems.” Am Pharm Rev. 2005;8(3):70-9.

5. Gao et al. “Development of supersaturatable self-emulsifying drug delivery system formulations for improving the oral absorption of poorly soluble drugs.” Expert Opin Drug Deliv. 2006;3(1):97-110.

6. Stegemann S. “Microemulsion capsule technology to optimize drug delivery.” Capsugel Library, BAS 265.

7. Cole ET. “Liquid-filled hard-gelatin capsules.” Capsugel Library, BAS 137.

8. Walker et al. “The filling of molten and thixotropic formulations into hard gelatin capsules.” J Pharm Pharmacol. 1980;32:389-393.

9. Consumer Insight & Strategy, The Natural Marketing Institute Supplement, OTC, Rx Database, April 2007.

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