Ann Newman - "Chemical Reactivity in Solid-State Pharmaceutics", S. R. Byrn, W. Xu, A. W. Newman

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      Publication Details (including relevant citation   information):

      Adv. Drug Delivery Rev., 2001,   48(1),115-136.


      Solid-state reactions that occur in drug substances and   formulations include solid-state phase transformations,   dehydration/desolvation, and chemical reactions. Chemical   reactivity is the focus of this chapter. Of particular interest   are cases where the drug-substance may be unstable or react with   excipients in the formulation. Water absorption can enhance   molecular mobility of solids and lead to solid-state reactivity.   Mobility can be measured using various methods including glass   transition (Tg) measurements, solid-state   NMR, and X-ray crystallography. Solid-state reactions of drug   substances can include oxidation, cyclization, hydrolysis, and   deamidation. Oxidation studies of vitamin A, peptides (Image -Ala-Image -Met, N-formyl-Met-Leu-Phe   methyl ester, and Met-enkaphalin acetate salt), and steroids   (hydrocortisone and prednisolone derivatives) are discussed.   Cyclization reactions of crystalline and amorphous   angiotensin-converting enzyme (ACE) inhibitors (spirapril   hydrochloride, quinapril hydrochloride, and moexipril) are   presented which investigate mobility and chemical reactivity.   Examples of drug-excipient interactions, such as transacylation,   the Maillard browning reaction, and acid base reactions are   discussed for a variety of compounds including aspirin,   fluoxitine, and ibuprofen. Once solid-state reactions are   understood in a pharmaceutical system, the necessary steps can be   taken to prevent reactivity and improve the stability of drug   substances and products.

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