Resumen de Do drugs really expire beyond the expiry date?: evaluation of expired (30 years from the manufacturing date) acetaminophen suspension and captopril tablet preparations
Kannan Sridharan, Satyendra Kumar Jain
Background: Medicinal products are not supposed to be used beyond their expiry date. A few studies indicate that expired medicinal products still retain active pharmaceutical ingredients (API) and hence, efficacy. There is a dearth of literature evaluating the medicinal products that have expired for several decades and particularly, with liquid dosage formulations. Objective: To evaluate the quantities of API and degradation products in the expired acetaminophen suspension and captopril tablets that expired around 30 years ago. Methods: Unused acetaminophen suspension with the expiry date October 1994, and captopril tablets with the expiry date January 1992 were evaluated. Quantification of active ingredients (acetaminophen in the suspension and captopril in the tablets) and degradation products (4-aminophenol and 4’-Chloroacetanilide in the suspension, and captopril disulphide in the tablets) was carried out using high-performance liquid chromatography adhering to United States Pharmacopoeia (USP) standards. A dissolution test was done for captopril tablets as per US Pharmacopoeia to determine in vitro bioavailability of the active ingredient. The quantities of active ingredients were considered acceptable if they fell within 90 to 110% of the standard preparations. The quantity of degradation products was evaluated according to the following USP limits: captopril disulphide (not more than 3%), 4-aminophenol (not more than 0.1%) and 4’-chlorocetanilide (not more than 10 parts per million). The limit for Dissolution of Captopril was NLT 80%(Q) dissolved in 20 minutes. Results: We evaluated the quantity of active ingredients and key degradation products in the expired acetaminophen suspension and captopril tablets. Active ingredients in the expired acetaminophen suspension and captopril tablets were 97.21 and 96.12%, respectively. Captopril tablets meet the requirement of Dissolution test as per US Pharmacopoeia with average value of 104.84%. Regarding degradation products for acetaminophen, only 4-aminophenol was detected and was within the acceptable limit. However, the quantity of captopril disulphide exceeded by 19.3% compared to the USFDA recommended limits. Methyl paraben was also present at 93.7% of stated claim in the acetaminophen suspension. Conclusion: We observed acceptable quantities of active ingredients in the expired acetaminophen suspension and captopril tablets even after 30 years past their expiry date. The degradation products were observed to be present within the specified limits in the acetaminophen suspension but exceeded by 19.3% in the captopril tablet. The pharmaceutical companies shall consider extending the shelf life of medicinal products and guidelines from the concerned regulatory agencies on this regard is urgently needed
