Soft gel finished dosage forms have gained in popularity over the last several years due to a number of factors. Soft gels are easy to swallow, and have the ability to mask odors and unpleasant tastes. They have an elegant appearance, readily dissolve in the gastric juices of the digestive tract, and they may enhance the bioavailability of the active ingredient.
The soft gel delivery system offers improved and consistent absorption of hydrophobic ingredients. Hydrophobic ingredients will not dissolve readily in water or in gastric or intestinal fluid, and when compounded in solid dosage forms, the dissolution rate may be slow and absorption may vary. Soft gel capsules also offer more protection for oxygen susceptible ingredients.
Defining Soft Gels
A soft gel capsule is a one-piece, hermetically sealed soft gelatin shell containing a liquid, a suspension or a semisolid called fill. The soft gel shell is usually comprised of a film-forming material such as gelatin, and a waterdispersible or water-soluble plasticizer (to impart flexibility). The soft gel shell could also include minor additives such as coloring agents, flavors, sweeteners and preservatives. Soft gel capsules can also be entericly coated for certain applications.
Gelatin is derived mostly from collagen by thermal denaturing with the aid of diluted acid or alkali. Gelatin contains a mixture of water-soluble proteins (84 percent to 90 percent), mineral salts (1 percent to 2 percent), and water (8 percent to 15 percent). These proteins contain a significant amount of the amino acids glycine, proline, hydroxyproline, glutamic acid, alanine, arginine, aspartic acid and lysine.
Gelatin is odorless, tasteless, colorless and insoluble in most organic solvents (such as alcohols, acetone or chloroform), but soluble in glycerin, diluted acids and alkalis. Gelatin swells and absorbs room-temperature waterup to five to 10 times its weight. It dissolves in hot water, and forms a gel upon cooling. Gelatin is considered an inactive ingredient by the Food and Drug Administration (FDA).
The main source of gelatin is collagen, which is found in the skin and bones of animals. Most of the soft gel capsules on the market are made from an animal source, bovine or porcine. However, vegetarian capsules such as Hydroxy Propyl Methyl Cellulose (HPMC), a carbohydrate derived wood pulp or raw cottonhave been developed as a soft gel alternative.
The bioavailability of the bio-actives in the soft gel depends on the dissolution of both its shell and fill. Dissolution of a chemical compound in the aqueous environment of the gastrointestinal tract is often the ratelimiting step in its absorption. If a substance, such as oil, is insoluble in the acidic solution of the gastrointestinal tract, then its dissolution can be slow. However, if this substance is administered in a vehicle in which it is soluble, then the absorption process may be enhanced. Polyethylene glycols, cyclodextrins, carboxymethylcellulose and emulsifiers have been used to enhance solubility of substances in water.
Dissolution problems of the soft gel shell are less common; they may become apparent upon aging as cross-linking causes the shell to become swollen, tough, rubbery and insoluble in water. High humidity causes the capsules to become soft, tacky and bloated, and may increase the likelihood of moisture migration from the shell into the fill material. Such a transfer can cause instability.
The formulation of capsule fill can be developed to fulfill the specifications and end-use requirements of the product. Capsulation of liquids that are immiscible with water and non-volatile, such as vegetable oils and vitamin E, are easy and require little or no formulation. However, solids that are not sufficiently soluble in liquids are encapsulated as suspensions. Such materials should have a particle size of 80 mesh or finer.
Encapsulation of suspensions is the most common form for a large group of soft gel dietary products. Suspension formulation requires a suspending agent to prevent the settling of the solids and to maintain homogeneity throughout capsulation. The most widely used suspending agent for oil-based formulation is wax (such as beeswax) and polyethylene glycols in a non-oil-base. Soft gels often contain high levels of lecithin, an emulsifier that allows water and oil (or water and an immiscible solvent) to mix to some degree.
The following types of compounds may not be suitable candidates for soft gel encapsulation:
- Liquids that can easily migrate through the gelatin shell, such as water (if more than 5 percent of the fill), and hygroscopic and volatile compounds;
- Aldehydes, which have the ability to harden the shell, affecting its dissolution properties;
- Acidic or alkaline solutions, unless they are adjusted to become neutral, as the pH can cause hydrolysis and leakage of the gelatin shell; and
- Water-soluble solid compounds that may affect the gelatin shell unless they are minor constituents of a formula or combined with a carrier that reduces their effect on the shell.
Yousry Naguib, Ph.D, is the manager of new product development with Soft Gel Technologies in Los Angeles. Naguib has written for numerous industry trade journals and conducted research at Tufts University in Boston and the U.S. Department of Agriculture (USDA).