Pharmaceutical stability

SHELFLIFE.dat The content (% of nominal) of two active components in a dosage form was assayed at various times (0-60 months) during a pharmaceutical stability trial to determine the acceptable shelf-life of the formulation the point at which the lower 90% confidence limit of the finear regression model intersects the 90%-of-nominal line gives the answer. Use with SHELFLIFE or LINREG. 

Uses. Manufacture of pharmaceuticals stabilizer in gasoline in production of insecticides and fungicides in manufacture of soaps and surfactants... 

If a method is developed for use in a strictly controlled regulatory environment such as for use during pharmaceutical stability studies or clinical trials then it is a good idea to test at three levels for the increased confidence this provides in the method. 

Peroxidation and free-radical formation should be considered as important aspects of pharmaceutical stability and quality of parenteral nutriton and intravenous drugs. Peroxidation and free-radical formation depend on environmental factors, such as storage conditions and container material, but are also influenced by formulation components or additives such as tocopherols and metabisulfite. Since the generation of these harmful species occurs generally at the time of use, manufacturing quality controls fail in demonstrating their existence. 

Kennon LJ. Use of models in determining chemical pharmaceutical stability. J Pharm Sci 1964 53(7) 815-818. 

The study of interactions between, and reactions induced by, the introduction of water to a sample is of importance in pharmaceutical stability. This is... 

Angberg M, Nystrom C, Cartensson S. Evaluation of heat-conduction microcalorimetry in pharmaceutical stability studies I. Precision and accuracy for static experiments in glass vials. Acta Pharm Suec 1988 25 307-320. 

As part of the ICH document development process, surveys of practices was taken in each geographical region by their respective Expert Working Groups. The American Survey was performed by the Pharmaceutical Stability Discussion Group (PSDG) with the assistance of its Facilitator, O Neill. 

The topic of Pharmaceutical Stability Testing actually started on June 5-7,1991 during discussions held in parallel with a conference organized by the APV in Darmstadt, Germany on the topic of "Stability Testing, New Trends and Requirements An International Symposium for the EC, Japan and the USA."... 

Lachman L, Cooper J. A comprehensive pharmaceutical stability-testing laboratory. JAPA 1959 XLVlll(4) 226-233. 

Piechocki J. Pharmaceutical photostabiUty how to select the right option. University of Wisconsin, Pharmaceutical Stability, Current Trends and Practices, Huntington Beach, CA, October 21-22, 2000. 

Thatcher SR, Mansfield RK, Miller RB, Davis CW, Baertschi SW. Pharmaceutical photostabiUty a technical and practical interpretation of the ICH guideline and its application to pharmaceutical stability Part 1. Pharm Tech 2001 25(3) 98-110. 

The process of determining the irradiation homogeneity as a function of a location on the exposure area is often referred to as "mapping," a term commonly used in the pharmaceutical stability field when referring to temperature homogeneity within a thermal stability chamber. It should be noted that such measurements do not provide any information about the SPD of the radiation impinging upon the samples. 

In 1959, after much research and based on the best principles then known, Lachman and Cooper (10), Lachman et al. (11) and Lachman et al. (12) published a series of papers detailing their development of a "Comprehensive Pharmaceutical Stability Testing Laboratory" which included photostability testing capabilities. This... 

Lachman L, Gooper J. A comprehensive pharmaceutical stability-testing laboratory. I. Physical layout of laboratory and facilities available for stability testing. J Am Pharm Assoc Am Pharm Assoc (Baltim) 1959 48(4) 226-233. 

Wall GM, Morgan J, Wrinkle M, Scott B, Dorsey E, Brammer 1. Irr The design of a Computerized Pharmaceutical Stability Monitoring System. Scientific Computing and Automation, June 13-16, 1998. 

Most protein stability studies have focused their interpretation on either a thermodynamic mechanism or a pure kinetic mechanism, and consequently there is some controversy and confusion over which mechanism is correct. Since the direction of a formulation development effort may depend on which theory is being followed, clarification of the roles of thermodynamic stabilization and kinetic stabilization in given stability problems would provide some practical benefit. This chapter is an attempt to provide such clarification. To this end, the major stresses, or destabilizing effects, that operate during the freeze-drying process are discussed, selected empirical observations regarding pharmaceutical stability in protein systems are presented, and the structure and dynamics in amorphous protein formulations are discussed. 

While FTIR spectroscopy may have some limitations as a quantitative predictor of the pharmaceutical stability of a protein [4], it seems clear that protein structure is often altered during the freeze-drying process, and the degree of structural perturbation is specific to the protein and quite specific to the formulation. 

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