Purpose: Federal law requires that drug products be labeled with an expiration date; beyond that date, drug products cannot legally be distributed, dispensed or used. The period over which a drug product should remain stable, effective and contain 90-110% of the active drug substance is called the shelf-life. Depending on the drug, drug manufacturers generally assign a shelf-life of 12 to 60 months to drug products, but the state pharmacy dispensing law requires that pharmacists set an expiration time of 6-12 months after the date of dispensing to patients; thus, the overall functional life of a drug is actually 12-18 months. The net result is that the expired drugs are discarded, costing the US economy billions of dollars each year in medication turnover. However, there is a paucity of scientific data to support the assumption that the functional life of many drugs can be extended without compromising their efficacy and safety. In this study, we sought to generate data with the goal of developing a scientific framework for extending the shelf-lives of frequently used drugs.
Methods: We selected nine frequently used drug formulations (tablets, capsules, syrups, inhalers and injectable solutions) of various drug classes, including antibiotic, antidiabetic, antiasthmatic, and blood-pressure-lowering medications. The drugs we have included in this study are amoxicillin, atenolol, albuterol, ceftriaxone, citalopram, diltiazem, famciclovir, glyburide, and simvastatin.
Soon after the expiration of the drugs, we assessed chemical properties such as hardness, disintegration, friability, drug release patterns, drug content, and pharmacokinetics of all selected drug products. We recorded these first set of experimental data as initial or baseline observations. For each drug product, we then compared the test results of expired drugs with those of unexpired products.
After conducting the initial physical analysis and animal pharmacokinetics (at month 0), we placed both expired and unexpired drug products in three climate chambers set at three different temperatures and relative humidity levels (25°C/60%RH, 30°C/65%RH, 45°C/70%RH) to simulate various storage conditions, as suggested by FDA regulations. The first condition (25°C/60%RH) represents storage at room environment, and the latter two (30°C/65%RH and 45°C/70%RH) represent stressed conditions. Periodically (at month 3, month 6 and month 12) collecting samples from these storage chambers, we repeated the experiments, as described above, for each product (Fig. 1).
Results: After first three months of storage (three months after the expiration), we observed no differences in the drug contents and physicochemical parameters on expired versus unexpired drugs. After six-month storage, we again assessed the physical properties, determined drug content and analyzed the drug release profiles of all drug products that have been stored in three climate chambers. Two expired drugs (simvastatin and glyburide), when stored at extreme condition (45°C/70%RH), showed changes in physical properties and reduced content compared to their expired counterparts. The only exception was expired amoxicillin that underwent degradation after six months of storage in all three storage conditions. In the twelve-month study, the expired lots of albuterol, simvastatin, and glyburide showed changes in physical properties and reduced content compared to their within-date counterparts, when stored at room (25°C/60%RH) and moderate (30°C/65%RH) climatic condition. The release patterns and drug content of other five drugs (for example famciclovir in Fig.2) did not change when stored for twelve in the room and moderate stressed condition. In addition to assessing the physical properties of all drug products, we have also studied the comparative pharmacokinetics of eight drug products at the end of six-month and twelve-month storage at moderate and extreme climatic conditions (30°C/65%RH and 45°C/70%RH), respectively in rats. The extent of drug absorption of the expired lots of amoxicillin, glyburide, and simvastatin was lower than that of unexpired drugs stored in the same condition in the six-month study. Whereas, the absorption profiles of albuterol, simvastatin, and glyburide also decreased in the twelve-month study, which were stored in 30°C/65%RH condition. However, the plasma concentration of expired lots of citalopram, atenolol, ceftriaxone, diltiazem, and famciclovir (Fig. 3) remained similar to that of within-date drugs during the twelve-month study.
Conclusion: After a year of storage at moderate to the elevated stress condition, five of the nine drugs were chemically and biologically stable. We are now in the process of studying the bioequivalence of expired and unexpired products. Based on the physical assessment and comparative pharmacokinetics in animals, we conclude that the shelf-life of many commercial drugs can potentially be extended beyond the conventionally set expiration dates.
Taslim Al-Hilal– Post Doctorate Research Associate, Texas Tech University Health Sciences Center, Amarillo, Texas
Ahmed Alobaida– Graduate Student/Research Assistant Ph.D. candidate, Texas Tech University Health Sciences Center, Amarillo
Hossam Kadry– Graduate Student, TTUHSC School of Pharmacy, Amarillo, Texas
Ali Keshavarz– Student, Texas Tech University Health Sciences Center, Amarillo, Texas
Fakhrul Ahsan– Texas Tech University Health Sciences Center, Amarillo, Texas