Stability of Drugs

Adsorption onto and Absorption into Containers and Transfer of Container Components into Pharmaceuticals

Pharmaceuticals may interact with packaging and containers, resulting in the loss of drug substances by adsorption onto and absorption into container components and the incorporation of container components into pharmaceuticals. Diazepam in intravenous fluid containers and administration sets exhibited a loss during storage due to adsorption onto glass and adsorption onto and absorption into plastics.740 741 Nitroglycerin, a liquid with a significant vapor pressure, is also significantly...

Drug Leakage from Liposomes

During storage, liposomes may exhibit physical instability, leading to leakage of intraliposomal entrapped drugs. In addition, chemical degradation of lipid membrane components resulting from oxidation and hydrolysis also changes drug release rates from liposomes. For example, phospholipid hydrolysis increased the permeability of a liposome membrane, resulting in increased leakage.716 Figure 180. DSC curves demonstrating crystallization of poly(Z-lactide) in microspheres following storage. (a)...

Isomerization and Racemization

Reported examples of isomerization of drug substances include trans-cis isomerization of amphotericin B Scheme 33 ,148 N,O-acyl rearrangement of cyclosporin A Scheme 34 ,149 and dienone-phenol rearrangement of steroids such as tirilazad Scheme 35 .150 Scheme 25. Hydrolysis of 5-azacytidine and cytarabine. Scheme 25. Hydrolysis of 5-azacytidine and cytarabine. Scheme 26. Other drug substances that are susceptible to hydrolysis, including alkyl halides, sulfides, and platinum compounds....

Chemical Degradation

The major known chemical degradation pathways for peptides and proteins are deami-dation, racemization, isomerization, hydrolysis, disulfide formation exchange, P-elimina-tion, and oxidation. Asparagine residues in peptides and proteins undergo deamidation via cyclic imide formation followed by subsequent hydrolysis to form the corresponding aspartic and wo-aspartic acid peptides. This mechanism occurs primarily under neutral-to-basic pH conditions. Deamidation of an asparagine residue to the...

Physical Degradation

Larger peptides and proteins are susceptible to noncovalent or physical changes (so-called 'physical degradation') in addition to chemical degradation. Physical degradation includes denaturation, aggregation, adsorption, and precipitation. Denaturation, that is, an alteration of tertiary (and or quaternary) structure, generally results in loss of bioactivity. Furthermore, exposure of hydrophobic groups upon denaturation often leads to adsorption onto surfaces, aggregation, and precipitation....

Degradation Of The Drug May Make The Product Esthetically Unacceptable

Chemical Stability of Drug Substances The most easily understood and most studied form of drug instability is the loss of drug through a chemical reaction resulting in a reduction of potency. Loss of potency is a well-recognized cause of poor product quality. In this chapter, the quantitation of chemical drug loss is discussed and analyzed. However, loss of drug potency per se by various pathways is only one of many possible reasons for quantitating drug loss. Identification of the product(s)...