Drug development stability

Drug substance/drug product purity, potency, and other testing Drug substance/drug product stability testing Method development, validation, and transfer Drug product formulation development... 

Recent developments in drug discovery and drug development spurred the need for novel analytical techniques and methods. In the last decade, the biopharmaceutical industry set the pace for this demand. The nature of the industry required that novel techniques should be simple, easily applicable, and of high resolution and sensitivity. It was also required that the techniques give information about the composition, structure, purity, and stability of drug candidates. Biopharmaceuticals represent a wide variety of chemically different compounds, including small organic molecules, nucleic acids and their derivatives, and peptides and proteins. 

Biological activity is not the only criterion required for drug development, as anyone who has been involved in this area is aware. Potency, toxicity, bioavailability, metabolic stability, and plasma half-life are only a few of the critical issues that must be addressed. Although satisfactory potency and spectrum activity had been achieved with WIN54954, which has been clinically evaluated, this compound lacked metabolic stability and consequently displayed a short half-life. 

The development of synthetic methods for the selective introduction of short-chain perfluoroalkyl groups into organic molecules is of interest in drug development [464]. Fluoromodifications often confer unique properties on a molecule, for example in terms of increased metabolic stability and lipophilicity and, as a consequence, the pharmacokinetic profiles are often improved [465]. Burger and coworkers developed a domino process consisting of a SN reaction combined with a Claisen and a Cope rearrangement which allows the transformation of simple fluorinated compounds into more complex molecules with fluoro atoms [466]. Treatment of furan 2-917 with 2-hydroxymethyl thiophene (2-918) in the presence... 

In summary, TLC analysis plays a critical role in the drug development process. Many instruments are available, and the technique is used for both quantitative and qualitative testing. i f determination, identity testing, and stability testing are just a few ways to utilize TLC. 

The present revised textbook on Pharmaceutical Drug Analysis caters for the much needed handbook and reference book, which is absolutely current with regard to the esteemed philosophy of analytical chemistry, an obvious solid support towards drug discovery, development, stability studies, bioavailability and pharmacokinetic studies, and above all the quality assurance of pure drugs together with their respective dosage forms. 

M. F. Powell, Peptide Stability in Drug Development In vitro Peptide Degradation in Plasma and Serum , Annu. Rep. Med. Chem. 1993, 28, 285-294 M. F. Powell, H. Grey, F. Gaeta, A. Sette, S. Colon, Peptide Stability in Drug Development a Comparison of Peptide Reactivity in Different Biological Media , J. Pharm. Sci. 1992, 81, 731-735. 

Drug development work also includes formulation, stability studies, and selection of drug delivery systems, as discussed in Section 5.6. Once the API has been prepared, excipients are added ... 

B. Stability Testing at Different Phases of the Drug Development Process... 

CE methods are developed and utilized in pharmaceutical QC for early to late phases of drug development. Chapter 4 covers the approaches for late-phase development for small molecules that can be used in early-phase development, as well as for large-molecular-weight compounds. Late-phase method development in pharmaceutical QC is performed for required stability studies and for release of the drug product or drug substance validation batches, and is intended to be transferred to the operational QC laboratories for release testing of the production batches. Preferably, late-phase methods should be fast, robust, reliable, and transferable. Therefore it is crucial to devote adequate time, thought, and resources to the development of such methods. 

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