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

• Published in: Journal of pharmaceutical sciences Vol. 107; no. 12; pp. 3080 - 3088
• Main Authors: Likar, Michael D., Carroll, Sophia C., Colgan, Stephen T., Yeoh, Thean, MacDonald, Bruce C., Johnson, Gail M., Space, J. Sean
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2018
• Subjects: Administration, Oral; Capsules - chemistry; Charcoal - chemistry; Cross-Linking Reagents - chemistry; dissolution; Drug Compounding - methods; Drug Packaging; Gelatin - chemistry; Humans; Humidity; moisture sorption; oral drug delivery; Pharmaceutical Preparations - administration & dosage; Pharmaceutical Preparations - chemistry; solid dosage form(s); Solubility; stability; Temperature; moisture sorption; solid dosage form(s); oral drug delivery; stability; dissolution
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1016/j.xphs.2018.08.009

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.