Understanding Softgel Basics

[Contract Manufacturing] Vol. 16 No. 9 September 2011

By Robin Koon, Contributing Editor

Soft-gelatin capsule (SGC) formulations are becoming more popular. These unique capsules are elastic and soft; can mask odors or unpleasant tastes; and are easy to swallow, which provides some distinct advantages over more traditional oral dosage forms such as tablets, hard-shell capsules and even liquids. They are suitable for encapsulation of non-aqueous or lipid formulations (solutions, suspensions or pastes). They are formed, filled and closed off in a single process. Any formulation in softgel can enhance absorption and bioavailability, or produce a quicker onset.

The finished product gelatin shell is primarily composed of gelatin, plasticizer, water and sometimes a colorant. The two types of capsules being produced today are animal-sourced gelatin (i.e., bovine, porcine, piscine) or vegetarian-sourced gelatin replacements (i.e., carrageenans and modified forms of starch and cellulose). The other ingredients used are a polyol plasticizing agent (e.g., glycerin, sorbitol, etc.), water and colors (natural or FD&C). Soft capsules used for oral use are typically round (spherical), oval or oblong in shape.

Products or compounds delivered in tablets or regular two-piece hard-shell capsules first need to dissolve before they can be absorbed, a process that can take as long as 45 minutes; softgels typically will disintegrate within 15 minutes, much faster than other dosage forms. Also, several softgel techniques can considerably improve drug/nutrient absorption and bioavailability.

Solublization

Solubility enhancement is one of the challenges in the formulation of pharmaceuticals and dietary supplements. According to industry statistics, almost 40 percent of all new pharmacologically potent molecules show poor aqueous solubility, leading to their low-effective concentration in biofluids, causing poor bioavailability that directly impacts its therapeutic action. Solublizing poorly absorbed ingredients, such as fat-soluble vitamins, nutrients and drugs (both water-insoluble and lipid-soluble compounds), is a useful option when formulating to enhancing bioavailability of both insoluble and lipid-soluble compounds.

Newer Emulsions

Fairly new drug technology delivery platforms have yielded a newer emulsification technology that can be used for poorly absorbed compounds. This delivery system can improve the absorption and bioavailability of poorly lipophilic (fat-soluble) nutrients into the body. The compounds are delivered to the water solution-based gut system in an emulsified form. The resulting micro-sized ingredients generally have three- to five-times higher bioavailability, and thereby significantly greater absorption into the body.

This technology’s advantage is that it can be dosed as a pre-concentrate in a softgel capsule. It is based on using emulsion pre-concentrates (surfactants and cosolvents) that spontaneously disperse to form emulsions upon the capsule opening in the stomach, where there is water. There are three closely related systems:

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[Contract Manufacturing] Vol. 16 No. 9 September 2011

 Self-emulsifying drug delivery system (SEDDS) typically produce emulsions with droplet sizes between 100 to 300 nm. SEDDS is an isotropic mixture of lipids/surfactants with an HLB less than 12.  Self-micro-emulsifying drug delivery systems (SMEDDS) form transparent micro emulsions with a droplet size of less than 50 nm. SMEDDS is an isotropic mixture with the inclusion of

hydrophobic surfactants with an HLB less than12--and with co-solvents (such as ethanol, propylene glycol and polyethylene glycol).  Self-nano-emulsified drug delivery system (SNEDDS) deals with nanotechnology. A nanoemulsion is thermodynamically stable system with the droplet size usually less than 100 nm.

Enteric Coating (EC)

EC is a technology available for softgel capsules. An enteric coating is a barrier applied to exterior of the softgel that controls the location in the digestive system where it disintegrate/ruptures; at this point, the released contents can then be absorbed. Enteric refers to the small intestine, therefore enteric coatings release the medication/nutrient when it reaches the small intestine. Such a coating can protect the stomach from the compound, protect the compound from the stomach, prevent gastric reflux of the compound and/or release the compound after the stomach.

Most enteric coatings work by presenting a surface that is insoluble at the highly acidic pH (2 to 3 pH, found in the stomach), but breaks down rapidly at a lower acidic pH (7 to 9 pH, found in the gut). Studies have typically reported no disintegration (rupture) of the softgel after two hours in a fluid simulating the stomach; total disintegration of the enteric coating after 12 minutes in a buffeted pH environment simulating the duodenum; and total disintegration (rupture) of the softgel within 60 minutes of entering the duodenum.

Softgels offer an amazing range of versatility to help improve and solve many formulation issues. One of the best benefits of using softgels is their ability to enhance nutrient bioavailability. Absorption matters, since product efficacy is directly dependent on how much of the nutrient is absorbed in the gut and into the bloodstream. Softgels are easy to swallow, offer excellent barrier properties and are accepted by customers.

Robin Koon is senior vice president at Best Formulations , and has more than 25 years of pharmaceutical experience in clinical pharmacy, as a retail drug chain executive overseeing operations, and in managed care.