The Cross-linking of Gelatin Capsules

　　Gelatin capsules can be cross-linked in storage, which contributes to slow disintegration and dissolution of capsules.

　　The cross-linking phenomenon of gelatin capsules indicates that the cross-linking reaction of the capsule shell occurs during storage, which causes the disintegration, dissolution and release efficiency of the preparation in the dissolution medium without enzymes to decrease.

　　Factors affecting crosslinking of gelatin capsule shell

　　(1) Selection of gelatin: The degree of crosslinking of gelatin is mainly affected by the amount of amino acid residues in gelatin. The lower the content of lysine and arginine in gelatin, the lower the degree and possibility of crosslinking.

　　(2) Water content of the capsule shell: When the water content in the capsule shell is high, it can accelerate the oxidation of gelatin and accelerate the production of imine intermediates.

　　(3) Plasticizers: Plasticizers such as glycerin and sorbitol will enhance the auto-oxidation of gelatin.

　　(4) Sunscreen and coloring agent: The added sunscreen and coloring agent may induce the production of aldehyde molecules, which will cause an acetal reaction with gelatin.

　　(5) Iron ion: The capsule contains iron ion, which makes the amino acid undergo Fenton chemical reaction to generate hydroxyl radical , which oxidizes the amino group and central carbon atom of the amino acid, resulting in gelatin cross-linking, but the iron ion content The effect on the cross-linking phenomenon cannot be determined.

　　Filling prescription factors

　　Filling prescription is the main factor of cross-linking in gelatin capsules:

　　(1) Drugs: drugs containing aldehyde groups react with gelatin residues to cause gelatin to crosslink.

　　(2) Pharmaceutical excipients: The added excipients contain preservatives, fatty substances or polyoxyethylene compounds, etc., which may promote the cross-linking of gelatin.

　　Storage conditions

　　Capsules should be stored at a temperature of 15-25 ℃, a relative humidity of 30%-40%, in a cool, dry and dark place. When the temperature rises, the degree of cross-linking of the capsule increases significantly, while when the temperature does not change, the relative humidity change has little effect on the degree of cross-linking of the capsule.

　　Slowly crosslinked empty capsules by Humanwellcaps:

　　Advantages: delay the time of cross-linking reaction between drug and capsule, and ensure the validity of shelf life

　　Scope of application: the content contains aldehyde, reducing sugar compounds and vitamin C and other groups, resulting in cross-linking reaction, leading to disintegration delay.

　　Contact us to know more about our Slowly crosslinked empty capsules