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 rate-limiting 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.

Dissolution problems of the soft gel shell are less common; they may become apparent upon aging, which are attributed to the cross-linking of gelatin. The cross-linking causes the formation of a swollen, tough, rubbery, and water-insoluble material.

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 chemical, physical and dissolution instability.

Due to the unique properties of SGC formulations, there exist many challenges to development of a good dissolution method. Generally, the drug is dissolved or suspended in oil before encapsulation. During dissolution, the oil may form a layer above the aqueous medium. In addition, oil droplets may become suspended in the medium. The existence of the lipid phase may hinder the release of the drug, and the oil layer or oil droplets may cause sampling problems. Furthermore, poor aqueous solubility of the drug may cause slow or incomplete dissolution