Pharmaceutical salt

Tire second chapter deals with rings systems which comprise two or more fused five- or six-membered heterocyclic rings. It is authored by Dr. I. Shcherbakova of NFS Pharmaceuticals, Salt Lake City, U.S.A., together with Drs. Elguero and Katritzky. 

The salting-in effect may be used to increase the solubility of a drug substance through the formation of associated ion pairs, most commonly making use of anionic countering (hydrochloride being the most popular). Detailed reviews of pharmaceutical salts have been published, which contain extensive tables of anions and cations acceptable for pharmaceutical use [44,47]. These articles also describe useful processes for the selection of the most desirable salt... 

Nuclear magnetic resonance spectroscopy is often used to quantify the ratio of API and counter-ion in a pharmaceutical salt, together with the type and quantity of hydrate or solvate molecules. 

Stahl, P.H. Wermuth, C.G. (Eds.), 2002, Handbook of Pharmaceutical Salts Properties, Selection and Use, Verlag Helvetica Chimica Acta, Zurich, Switzerland. 

Stahl PH, Wermuth CG, eds. Handbook of Pharmaceutical Salts. Weiheim Wiley-VCH, 2002. 

The physicochemical properties of a drag substance must be known and well characterized (e.g., solubility, acidic constant (pKa), distribution coefficient in octanol water (logP value), pH-dependent distribution coefficient (logD), and its physical state, e.g., morphology or salt stochiometry — if the drag forms a pharmaceutical salt). 

Z. Lin, L. Zhou, A. Mahajan, S. Song, T. Wang, Z. Ge and D. Elhson, Real-time end point monitoring and determination for a pharmaceutical salt formation process within in-hne ET-IR spectroscopy, J. Pharm. Biomed. Anal.,... 

Stahl, P. FI. and C. G. Wermuth (eds.) (20Q2 ndbook of Pharmaceutical Salts—Properties, Selection, and Use, Wiley-VCH, New York. 

Bowker, M. J. 2002. A procedure for salt selection and optimizatioridindbook of Pharmaceutical Salts ... 

Afermuth, C. G and P. H. Stahl. 2002. Selected procedures for the preparation of pharmaceutically acceptable salts. InHandbook of Pharmaceutical Salts Properties, Selection, and Use, edited by P. H. Stahl and C. G. V fermuth, 249-263. New York Wiley-VCH. 

HNOs) aqua fortis. A corrosive liquid with a sharp odour that acts as a strong acid when dissolved in water. Nitric acid is used to synthesise ammonium nitrate for fertilisers, and is also used in the manufacture of explosives, dyes, and pharmaceuticals. Salts of nitric acid are called nitrates. 

Since powder dissolution is influenced by changing surface area, it is not useful for delineating the effects of polymorphs, hydrates, and pharmaceutical salts. Instead, the intrinsic dissolution rate (IDR) is used. The IDR studies are conducted at a constant surface area and hence the dissolution rate observed is only a function of the intrinsic solubility of the drug. The Noyes-Whitney equation is modified for IDR, where the surface area is kept constant, and Equation (17) reduces to... 

Table 1 Potential counterions used in the preparation of pharmaceutical salts...

In addition to overall solubility, salts can have a significant impact on the dissolution rate of a solute. Hence, solubility considerations are important factors to be assessed when trying to make a rational choice of an appropriate pharmaceutical salt. ... 

In addition to its synthetic utility, MSA is employed as an amine-salt former in pharmaceutical final dosage forms. Other sulfonic acids are also used as pharmaceutical salt formers, but much less frequently. 

Pudipeddi M, Serajuddin ATM, Grant DJW, and Stahl PH. Solubility and Dissolution of Weak Acids, Bases, and Salts. In Stahl PH and Wermuth CG. Handbook of Pharmaceutical Salts. Wiley-VCH, Weinheim, Germany, 2002, pp. 19-39. 

Stahl PH and Wermuth CG. Handbook of Pharmaceutical Salts. Wiley-VCH, Weinheim, Germany, 2002, p. 374. 

Solubility determination for pharmaceutical salts using the equilibrium method may be challenging for certain compounds such as those with poor intrinsic solubility. Theoretically, after an excess amount of solid salt is equilibrated in water, the solution concentration at equilibrium should represent the solubility of the salt. However, this is only true if the pH of the saturated solution is below pH. For compounds with low intrinsic solubilities and weak basicity or acidity, their salts may convert to the unionized form in the solubility medium. In such... 

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