Enhancing the Dissolution Stability of Hard Gelatin Capsules Using Activated Carbon as a Packaging Component.

Hard gelatin capsule (HGC) shells are widely used to encapsulate drugs for oral delivery but are vulnerable to gelatin cross-linking, which can lead to slower and more variable in vitro dissolution rates. Adding proteolytic enzymes to the dissolution medium can attenuate these problems, but this complicates dissolution testing and is only permitted by some regulatory authorities. Here, we expand the scope of our previous work to demonstrate that canisters containing activated carbon (AC) or polymeric films embedded with AC particles can be used as packaging components to attenuate gelatin cross-linking and improve the dissolution stability of hard gelatin-encapsulated products under accelerated International Council for Harmonisation conditions. We packaged acetaminophen and diphenhydramine HCl HGCs with or without AC canisters in induction-sealed high-density polyethylene bottles and with or without AC films in stoppered glass vials and stored these samples at 50°C/75% relative humidity through 3 months and at 40°C/75% relative humidity for 6 months. Samples packaged with AC canisters or AC films dissolved more rapidly than samples packaged without AC when differences were observed. These results demonstrate that different sources and formats of AC can enhance the dissolution stability of HGCs packaged in bottles and other potential packaging systems such as blister cards.

Use of Activated Carbon in Packaging to Attenuate Formaldehyde-Induced and Formic Acid-Induced Degradation and Reduce Gelatin Cross-Linking in Solid Dosage Forms.

Formaldehyde and formic acid are reactive impurities found in commonly used excipients and can be responsible for limiting drug product shelf-life. Described here is the use of activated carbon in drug product packaging to attenuate formaldehyde-induced and formic acid-induced drug degradation in tablets and cross-linking in hard gelatin capsules. Several pharmaceutical products with known or potential vulnerabilities to formaldehyde-induced or formic acid-induced degradation or gelatin cross-linking were subjected to accelerated stability challenges in the presence and absence of activated carbon. The effects of time and storage conditions were determined. For all of the products studied, activated carbon attenuated drug degradation or gelatin cross-linking. This novel use of activated carbon in pharmaceutical packaging may be useful for enhancing the chemical stability of drug products or the dissolution stability of gelatin-containing dosage forms and may allow for the 1) extension of a drug product's shelf-life when the limiting attribute is a degradation product induced by a reactive impurity, 2) marketing of a drug product in hotter and more humid climatic zones than currently supported without the use of activated carbon, and 3) enhanced dissolution stability of products that are vulnerable to gelatin cross-linking.