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.
Global CMC, Pfizer Worldwide Research and Development, Groton, Connecticut 06340. Electronic address: stephen.t.colgan@pfizer.com.
Stephen T
ST
Colgan
Analytical Research and Development, Pfizer Worldwide Research and Development, Groton, Connecticut 06340.
Todd C
TC
Zelesky
Analytical Research and Development, Pfizer Worldwide Research and Development, Groton, Connecticut 06340.
Raymond
R
Chen
Analytical Research and Development, Pfizer Worldwide Research and Development, Groton, Connecticut 06340.
Michael D
MD
Likar
Pharmaceutical Research and Development, Pfizer Worldwide Research and Development, Groton, Connecticut 06340.
Bruce C
BC
MacDonald
Chemical Research and Development, Pfizer Worldwide Research and Development, Groton, Connecticut 06340.
Joel M
JM
Hawkins
Eurofins Lancaster Laboratories PSS 3096, Lancaster, Pennsylvania 17601.
Sophia C
SC
Carroll
Analytical Research and Development, Pfizer Worldwide Research and Development, Groton, Connecticut 06340.
Gail M
GM
Johnson
Analytical Research and Development, Pfizer Worldwide Research and Development, Groton, Connecticut 06340.
J Sean
JS
Space
Analytical Research and Development, Pfizer Worldwide Research and Development, Groton, Connecticut 06340.
James F
JF
Jensen
Analytical Research and Development, Pfizer Worldwide Research and Development, Groton, Connecticut 06340.
Vincent A
VA
DeMatteo
D002214:Capsules; D002606:Charcoal / Q000737:chemistry*; D003432:Cross-Linking Reagents; D004304:Dosage Forms; D004340:Drug Contamination; D004349:Drug Packaging; D004355:Drug Stability; D005079:Excipients; D005557:Formaldehyde / Q000737:chemistry*; D005561:Formates / Q000737:chemistry*; D005780:Gelatin / Q000737:chemistry*; D013607:Tablets; D000068580:Varenicline / Q000737:chemistry
D002214:Capsules; D003432:Cross-Linking Reagents; D004304:Dosage Forms; D005079:Excipients; D005561:Formates; D013607:Tablets; C030544:formic acid; D002606:Charcoal; D005557:Formaldehyde; D005780:Gelatin; D000068580:Varenicline
chemical stability; dissolution; physical stability; solid dosage form; stability