Stability of ranitidine syrup re-packaged in unit-dose containers.

PURPOSE: The stability of ranitidine syrup re-packaged in unit-dose containers was studied. METHODS: Oral ranitidine hydrochloride syrup containing 16.8 mg/mL of ranitidine hydrochloride (equivalent to 15 mg of ranitidine) in original bulk containers and re-packaged in unit-dose amber-colored glass bottles sealed with aluminum caps were obtained from commercial sources. For extended-stability determinations, samples were stored for 52 weeks at 25 degrees C and 40% relative humidity and analyzed at 0, 4, 13, 26, 39, and 52 weeks. For accelerated stability determinations, samples were stored for 13 weeks at 40 degrees C and 25% relative humidity and analyzed at 0, 4, 9, and 13 weeks. Stability was assessed using high-performance liquid chromatography and by measuring changes in pH and sample weight. The principal impurity and total impurities were also measured. RESULTS: No significant changes in pH were demonstrated, and all values remained well within acceptable limits. The weight change in samples was greater for re-packaged samples stored in accelerated conditions compared with that of samples in the original packaging; however, the differences were not significant. Ranitidine hydrochloride samples in both types of packaging remained stable when stored at 25 degrees C and 40% relative humidity for 52 weeks and at 40 degrees C and 25% relative humidity for 13 weeks. The impurity profiles remained within acceptable limits for all samples. CONCLUSION: Re-packaged ranitidine syrup was stable for up to 52 weeks when stored at 25 degrees C and 40% relative humidity and for up to 13 weeks when stored at 40 degrees C and 25% relative humidity.

PQRI recommendations on particle-size analysis of drug substances used in oral dosage forms.

This document provides information for the Pharmaceutical Industry and the Federal Drug Administration (FDA) regarding the selection of suitable particle-size analysis techniques, development and validation of particle-size methods, and the establishment of acceptance criteria for the particle size of drug substances used in oral solid-dosage forms. The document is intended for analysts knowledgeable in the techniques necessary to conduct particle-size characterization (a table of acronyms is provided at the end of the document). It is acknowledged that each drug substance, formulation, and manufacturing process is unique and that multiple techniques and instruments are available to the analyst.

Stability profiles of drug products extended beyond labeled expiration dates.

The American Medical Association has questioned whether expiration dating markedly underestimates the actual shelf life of drug products. Results from the shelf life extension program (SLEP) have been evaluated to provide extensive data to address this issue. The SLEP has been administered by the Food and Drug Administration for the United States Department of Defense (DOD) for 20 years. This program probably contains the most extensive source of pharmaceutical stability data extant. This report summarizes extended stability profiles for 122 different drug products (3,005 different lots). The drug products were categorized into five groups based on incidence of initial extension failures and termination failures (extended lot eventually failed upon re-testing). Based on testing and stability assessment, 88% of the lots were extended at least 1 year beyond their original expiration date for an average extension of 66 months, but the additional stability period was highly variable. The SLEP data supports the assertion that many drug products, if properly stored, can be extended past the expiration date. Due to the lot-to-lot variability, the stability and quality of extended drug products can only be assured by periodic testing and systematic evaluation of each lot.