Chemical stability hydrolysis

Raw juice is heated, treated sequentially with lime (CaO) and carbon dioxide, and filtered. This accomplishes three objectives (/) microbial activity is terminated (2) the thin juice produced is clear and only lightly colored and (J) the juice is chemically stabilized so that subsequent processing steps of evaporation and crystalliza tion do not result in uncontrolled hydrolysis of sucrose, scaling of heating surfaces, or coprecipitation of material other than sucrose. 

Phosphoric and polyphosphoric acid esters Perfluorinated anionics Sulfonic acid salts Strong surface tension reducers Good oil in water emulsifiers Soluble in polar organics Resistant to biodegradation High chemical stability Resistant to acid and alkaline hydrolysis... 

Yang C, Gao H, Mitra AK (2001) Chemical stability, enzymatic hydrolysis, and nasal uptake of amino acid ester prodrugs of acyclovir. J Pharm Sci. 90 617-624. 

The last group of aliphatic amides to be discussed are the tertiary amides, which, by definition, carry two alkyl substituents on the N-atom. Investigations of their chemical stability have disclosed a surprising difference between tertiary and secondary amides, since the rate of acid-catalyzed hydrolysis of N,N-dimethyl amides is higher than that of A-methyl amides. If steric fac-... 

Hydrazides are formed by the acylation of hydrazines, and have a C-N bond of rather low chemical stability toward hydrolysis. It is, therefore, not surprising that the cleavage of this bond represents a major metabolic pathway for most hydrazides. The reaction is catalyzed by amidases since it can be inhibited by O-ethyl 0-(4-nitrophenyl) phenyl phosphothionate or bis(4-nitrophenyl) phosphate, which are classical inhibitors of this enzyme. 

A. H. Kahns, H. Bundgaard, A-Acyl Derivatives as Prodrug Forms of Amides Chemical Stability and Enzymatic Hydrolysis of Various A-Acyl and A-Alkoxylcarbonyl Amide Derivatives , Int. J. Pharmaceut. 1991, 71, 31-43. 

Most of this chapter (Sect. 5.2) focuses on the chemical reactivity of the lactam bond and its hydrolysis by bacterial enzymes (lactamases), rather than to its metabolic degradation by mammalian enzymes. This is in contradistinction to other chapters of this book, where metabolism in mammals is the focus of discussion. The reason for the attention given here to the chemical reactivity and bacterial degradation of /3-lactams is that these issues have caused more pharmaceutical and clinical problems than metabolic hydrolysis. This also explains why the chemical stability of /3-lactams and their resistance to /3-lactamases have been the subject of countless studies, while the metabolism of these compounds has received less attention. 

An example of a protected catechol is provided by the diacetyl prodrug of ABT-431, a potent Drreceptor agonist. The chemical stability of the prodrug was markedly better than that of the drug. Hydrolysis of the former in rat plasma occurred with a tm value of less than a minute [98]. An example of a triacetate is 2, 3, 5 -triacetyl-6-azauridine, an orally active prodrug of the antipsoriasis and antineoplastic drug 6-azauridine [99],... 

L. K. Wadhwa, P. D. Sharma, Glycolamide Esters of 6-Methoxy-2-naphthylacetic Acid as Potential Prodrugs-Physicochemical Properties, Chemical Stability and Enzymatic Hydrolysis , Int. J. Pharm. 1995, 118, 31-39. 

C. Yang, H. Gao, A. K. Mitra, Chemical Stability, Enzymatic Hydrolysis, and Nasal Uptake of Amino Acid Ester Prodrugs of Acyclovir ,. /. Pharm. Sci. 2001, 90, 617-624. 

Similar to accelerated studies, stress tests give a general picture of the chemical stability and degradation pathways under exaggerated conditions, such as under extreme pH conditions (acids and bases), heat, oxidative or reductive conditions, hydrolysis, and light irradiation (light irradiation tests at not less than 1.2 million lux hours are formalized as described in ICH QIB). These mostly non-formalized stress tests are only evaluated over a short term, e.g., 1 month. 

The solid matrix of SLN protects the drug from hydrolysis and oxidation. Chemical stability of tocopherol and retinol improves considerably [17,39], with tocopherol improving by 57% compared with an aqueous dispersion. The degree of retinol stabilization depends on the nature of lipid and surfactant [39]. For each drug, the optimal preparation has to be defined individually. 

The chemical stability of the amide bond is high. When the surfactant containing an amide bond was subjected to 1 M sodium hydroxide during five days at room temperature, only 5% of the amide surfactant was cleaved. The corresponding experiment performed in 1 M HCl resulted in no hydrolysis. The amide bond was, however, found to be slowly hydrolyzed when lipase from Candida antarctica or peptidase was used as catalyst. Amidase and lipase from Mucor miehei was found to be ineffective. Despite the very high chemical stability, the amide surfactant biodegrades by a similar path in the... 

Proteins, peptides, and other polymeric macromolecules display varying degrees of chemical and physical stability. The degree of stability of these macromolecules influence the way they are manufactured, distributed, and administered. Chemical stability refers to how readily the molecule can undergo chemical reactions that modify specific amino-acid residues, the building blocks of the proteins and peptides. Chemical instability mechanisms of proteins and peptides include hydrolysis, deamidation, racemization, beta-elimination, disulfide exchange, and oxidation. Physical stability refers to how readily the molecule loses its tertiary and/or sec-... 

The chemical stability of dinitrodiglycol resembles that of nitroglycerine. Heated with water it undergoes hydrolysis more slowly than nitroglycerine on being maintained for 5 days at 60°C only 0.003% is decomposed. Hydrolysis in the presence... 

The vast differences in the functional groups possessed by the side chains allows for their chromatographic separation. However, closely related compounds can still be tough to resolve. For example, leucine and isoleucine tend to afford very tight resolution. The chemical differences in the side chains can be very problematic when it comes to sample preparation. This is especially true for the acid hydrolysis of proteins to liberate their constituent amino acids in the free form. The different functional groups exhibit different chemical stabilities in an acid environment. 

Cellulose acetate (CA), of poor chemical stability, tends to hydrolyze over time, is subject to biological attack, and can operate at only a limited pH range of 3.0 to 6.5 at 0 to 30°C. It is widely available at low cost and is tolerant of continuous low-level chlorine exposure, such as is found in city water). Often blended with cellulose triacetate (CTA), which provides reasonable hydrolysis and compaction characteristics. 

Drugs in solution formulations may be more susceptible to chemical reactions leading to degradation. The most common reactions are hydrolysis, oxidation, and reduction. Usually, the reaction rate or type is inLuenced by pH. For example, the hydrolysis of acetylsalicylic acid (aspirin) is pH dependent, and its pH-rate proLle shows a large and complex variation dfrls to four distinct mechanistic patterns (Alibrandi et al., 2001). Therefore, it is essential to monitor and understand the chemical stability of the drug in pH-adjusted formulations. 

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