Stability of drugs and medicines

Drugs sometimes have quite complicated chemical structures and are, by definition, biologically active compounds. It should not, therefore, come as a surprise that these reactive molecules undergo chemical reactions that result in their decomposition and deterioration, and that these processes begin as soon as the drug is synthesised or the medicine is formulated. Decomposition reactions of this type lead to, at best, drugs and medicines that are less active than intended (i.e. of low efficacy)-, in the worst-case scenario, decomposition can lead to drugs that are actually toxic to the patient. This is clearly bad news to all except lawyers, so the processes of decomposition and deterioration must be understood in order to minimise the risk to patients. 

There are almost as many ways in which drugs can decompose as there are drugs in the British Pharmacopoeia, but most instability can be accounted for by the processes of oxidation and hydrolysis. 

Stage 1 Chain initiation involves homolytic fission to produce free 

Stage 2 Chain propagation free radicals are consumed and 

Reactive free radicals join together to form covalent bonds. This effectively ends the chain reaction process and produces stable compounds. 

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Shen, M.,Xiao,Y., Golbraikh,A., Gombar, V.K. and Tropsha, A. (2003) Development and validation of fc-Nearest-Neighbor QSPR models of metabolic, stability of drug candidates. Journal of Medicinal Chemistry, 46, 3013-3020. 

Every plant which manufactures drugs shall be provided with a quality control service under the direction of a quality control head according to section 3. This service will control ail of the starting material, will monitor the production stages in terms of quality and will verify the quality and stability of the manufactured medicinals. 

A further aspect that may add to the development work relates to the method of administration. In addition to the standards methods of administration associated with human medicines, veterinary medicines may be introduced to animals through medicated feeds. Such practices have been most commonly associated with the use of antibiotics or other substances to enhance animal performance under intensive farming systems. The use of medicated feeds has been phased out in Europe since the end of 2005, with the exception of coccidiostats and histomonostats intended to kill or inhibit protozoa. In the U SA, however, medicated feeds are still commonplace. Thus, the developer may have to consider the stability and appropriate labelling of the drug when compounded into medicated feeds. 

Used in the production of carbamates that are used to synthesize dyes, drugs, veterinary medicines, herbicides, and insecticides as a solvent in the photographic industry used as a stabilizer for PVC. 

Noncovalent interactions play a special role in synthetic procedures used to assemble various types of supramolecular species. These syntheses rely on the stabilization provided by non-covalent interactions between recognition sites incorporated within precursors. Various types of non-covalent interactions can be used as a recognition motif utilized to guide the synthesis.Targeted synthesis of macro- and supramolecular structures of various sizes, shapes, and functionality has now become possible. Supramolecular chemistry offers incredible applications in various fields such as medicinal chemistry (drug delivery systems),host-guest chemistry,catalysis,and molecular electronics. ... 

By this we mean interactions that occur after the medicine has been administered to the patient. For the most part, they are physical interactions. However, the major distinctions are that the interaction is between the medicine (including excipients) and the body fluids, primarily comprising aqueous solutions, and that they have the potential to influence the rate of absorption of the drug. They will vary depending on the route of administration. Because physiological and biopharmaceutical interactions are so important, and they are not specifically linked, for example, to the stability of the medicinal product, and also because they occur after the medicine has been administered to the patient, they have been included as a special category for the purposes of this discussion. The importance and potential impact of biopharmaceutical interactions of excipients has been recognized for some years (see for example Ref. 29). 

Vinblastine (6.73) is an antimitotic drug that prevents polymerization of tubulin (Figure 6.26). When incubated with tubulin, vinblastine complexes in a 1 1 ratio with tubulin proteins. By blocking polymerization, vinblastine prevents microtubule formation and therefore mitosis. In contrast, paclitaxel (Taxol, 6.74) and epothilone B (6.75) stabilize aggregated tubulin. As a result, in the presence of paclitaxel and epothilone B, cells form static bundles of microtubules that are nonfunctional. Vinblastine and paclitaxel are both approved for clinical use against cancer. Ixabepilone (6.76), an analogue of epothilone B (6.75), has been approved by the FDA for treatment of certain forms of breast cancer. The European Medicines Agency (EMEA) did not approve ixabepilone out of concern over severe side effects.27... 

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