Stability, drug

Diclofenac sodium fi-CD Thermal stability in solid state 47 

3 Solid dosage forms kinetics of chemical decomposition 1 1 0 

Factors influencing drug stability 1 13 Stability testing and prediction of shelf-life 127 Summary 136 

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Phenyl-2//-triazolo[4,5-/]quinoline was prepared and used as optical bright-ener, light, and drug stabilizer (86GEP1), whereas 3,5,7-3//-trimethyl-triazolo[4, 5-/]quinoline was identified by gas chromatography/mass spectrometry as a water pollutant of the Shinano River (Japan) (82MI6). 

The stability of suspensions, emulsions, creams, and ointments is dealt with in other chapters. The unique characteristics of solid-state decomposition processes have been described in reviews by D. C. Monkhouse [79,80] and in the monograph on drug stability by J. T. Carstensen [81]. Baitalow et al. have applied an unconventional approach to the kinetic analysis of solid-state reactions [82], The recently published monograph on solid-state chemistry of drugs also treats this topic in great detail [83],... 

Fig. 6 Solubility effects on drug stability curve A, drug formulated as lOmg/mL solution (q/2 = 1 year) curve B, drug formulated as a suspension with a saturated solubility of 1 mg/mL (ti/2 = 7.3 years). 

Buffer salts also can exert a secondary salt effect on drug stability. From Table 5 and Fig. 5 it is clear that the rate constant for an ionizable drug is dependent on its pKa. Increasing salt concentrations, particularly from polyelectrolytes such as citrate and phosphate, can substantially affect the magnitude of the pKa, causing a change in the rate constant. (For a review of salt effects, containing many examples from the pharmaceutical literature see Ref. 116.)... 

Higuchi and Lachman [122] pioneered the approach of improving drug stability by complexation. They showed that aromatic esters can be stabilized in aqueous solutions in the presence of xanthines such as caffeine. Thus, the half-lives of benzocaine, procaine hydrochloride, and tetracaine are increased by approximately two- to fivefold in the presence of 2.5% caffeine. This increase in stability is attributed to the formation of a less reactive complex between caffeine and the aromatic ester. Professor K. A. Connors has written a comprehensive textbook that describes methods for the measurement of binding constants for complex formation in solution—along with discussions of pertinent thermodynamics, modeling statistics,... 

J. T. Carstensen, Drug Stability, Marcel Dekker, New York, 1991, p. 60. 

Behind the relatively straightforward compositional nature of ophthalmic solutions, suspensions, and ointments, however, lie many of the same physicochemical parameters that affect drug stability, safety, and efficacy, as they do for most other drug products. But additionally, specialized dosage forms present the ophthalmic product designer with some extraordinary compositional and manufacturing challenges. These... 

Nebulizer formulation conforms to sterile product preparation, which means that drug stability in solution in the presence of additives must be evaluated. Historically, it was sufficient to use antimicrobial agents in the formulation, notably benzalkonium chloride. Adding antimicrobials is not now considered an acceptable approach to the formulation of nebulizer solutions. The solubility of the drug is important since it may impact upon the performance of the solution in a selected nebulizer. Additives may form complexes with the drug. 

Drug Stability Guidelines, Center for Veterinary Medicine, Food and Drug Administration, Fourth Revision, 1990, pp. 2-23. 

Drug Stability Principles and Practices, Jens T. Carstensen... 

Drug Stability Principles and Practices, Third Edition, Revised and Expanded, edited by Jens T. Carstensen and C. T. Rhodes... 

Frokjaer, S and Otzen, D. 2005. Protein drug stability a formulation challenge. Nature Reviews Drug Discovery 4(4), 298-306. 

Yarwood, R. J., Phillips, A. J. Processing factors influencing the stability of freeze-dried sodium ethacrinate. Pharmaceutical Technology Drug Stabilization, p. 40-48, 1989. Edited by Rubinstein, Michael, Verlag Ellis Horwood, Chichester, UK. 

Biologically active carbon, 7 7 803 Biological media, drug stability in, 9 53 Biological nanomachines, 7 7 45 Biological nitrogen fixation, 77 295-311, 316... 

Drug stability in experimental set-up. Demonstrate minimal degradation of drug substance in buffer and also adsorption onto experimental apparatus... 

A. G. De Oliveira, I. M. Cuccovia, H. Chaimovich, Micellar Modification of Drug Stability Analysis of the Effect of Hexadecyltrimethylamonium Halides on the Rate of Degradation of Cephaclor , J. Pharm. Sci. 1990, 79, 37-42. 

In this section, discussion of physicochemical profiling is limited to solubility, permeability, drug stability, and limited solid-state characterization (as we will see in Section 3.4, there are other physical-mechanical properties that must also be considered). For convenience, methods available for physicochemical profiling are discussed under the following categories computational tools (sometimes referred to as in silico tools), HTS methods, and in-depth physicochemical profiling.16... 

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