Crosslinking Studies in Gelatin Capsules Treated with Formaldehyde and in Capsules Exposed to Elevated Temperature and Humidity

Package Selection for Moisture Protection for Solid, Oral Drug Products

“…28,29 Crosslinked gelatin will often be slow to dissolve, and cause the dissolution rate of the drug to be retarded in standard dissolution testing. In the presence of the enzyme pepsin at pH 1.2 (or pancreatin at pH 7.2), the gelatin release rate is often recovered.…”

Molecular changes in gelatin aging observed by NIR and fluorescence spectroscopy

“…Historically, a decrease in dissolution was first revealed in hard gelatin capsules exposed to various humidity conditions (Khalil, Ali, & Abdel Khalek, 1974), and has been related to the tendency of gelatin chains to form cross-links. Cross-links appear in high temperature and humidity conditions, UV light, or in the presence of some chemical compounds, such as aldehydes (Digenis et al, 1994;Ofner, Zhang, Jobeck, & Bowman, 2001). The latter can derive from sugars, lipids or oxidation products of basic amino acids in gelatin or from the drugs contained in the capsules (Ofner et al, 2001).…”

“…Cross-links appear in high temperature and humidity conditions, UV light, or in the presence of some chemical compounds, such as aldehydes (Digenis et al, 1994;Ofner, Zhang, Jobeck, & Bowman, 2001). The latter can derive from sugars, lipids or oxidation products of basic amino acids in gelatin or from the drugs contained in the capsules (Ofner et al, 2001). Cross-links in gelatin chains create very high molecular weight fractions (>800 kDa) above the native molecular weight of collagen g-chains (Dupont, 2002).…”

“…For instance, high temperature is suspected to induce cross-linking involving amine functions, reducing solubility in water (Digenis et al 1994). However, Ofner et al (2001) showed that the number of amines was stable with aging, whereas solubility still decreased.…”

Effects of alga polysaccharide capsule shells on in-vivo bioavailability and disintegration

“…Gelatin is a collagen protein, originating from the bones and skin of cattle and pigs, as it has properties that make it suitable for capsule manufacturing, such as thermo-reversibility, film-forming ability, and a triple-helix structure. However, there are some drawbacks, such as the cross-linking reaction of gelatin (Digenis et al, 1994;Brown et al, 1998;Ofner et al, 2001).…”