Nicotinic acid titratable acidity

Niacin should be instituted at the lowest dose and gradually titrated to a maximum dose of 2 grams daily for ER and SR products and no more than 5 grams daily for IR products. FDA-approved niacin products are preferred because of product consistency. Moreover, niacin products labeled as no flush don t contain nicotinic acid and therefore have no therapeutic role in the treatment of lipid disorders.28 The time until maximum effect on lipids for niacins is generally 3 to 5 weeks. 

Weak acid/strong base titration is used in the pharmacopoeial assays of benzoic acid, citric acid, chlorambucil injection, mustine injection, nicotinic acid tablets and undecanoic acid. 

Dosing of nicotinic acid should be titrated to minimize adverse effects. An initial dose of 50 to 100 mg t.i.d. often is used with immediate-release tablets. The dose then is gradually increased by 50 to 100 mg every 3 to 14 days, up to a maximum of 6 g/day, as tolerated. Therapeutic monitoring to assess efficacy and prevent toxicity is essential until a stable and effective dose is reached. Similar dosing escalations are available for extended-release products, with doses normally starting at 500 mg once daily at bedtime. (7,15,21). 

Here 25.0 mL of 0.100 M nicotinic acid, a weak acid, is titrated by 0.100 M NaOH. Note that bromcresol green changes color during the early part of the titration, well before the equivalence point. Phenolphthalein changes color where the pH changes rapidly (near the equivalence point). Thus, phenolphthalein could be used as an indicator for the titration, whereas bromcresol green could not. 

Note also that the equivalence point for the titration curve of nicotinic acid occurs on the basic side. This happens because at the equivalence point the solution is that of the salt, sodium nicotinate, which is basic from the hydrolysis of the nicotinate ion. The optimum choice of indicator would be one that changes color over a range that includes the pH of the equivalence point... 

Calculate the pH of the solution at the equivalence point when 25 mL of 0.10 M nicotinic acid is titrated by 0.10 M sodium hydroxide. Ka for nicotinic acid equals... 

Figure 27 Electropherogram of a mixture of nicotinic acid and related compounds. Conditions applied voltage, 25 kV sample injection, 7 s pneumatic injection capillary, unmodified fused-silica (57 cm X 50 xm i.d.) buffer, acetonitrile-buffer [10 mM KH2PO4 (pH 2.50), titrated with phosphoric acid] detection wavelength, 254 nm. iV -MNA, iV -methylnicotinamide (see Fig. 1). (From Ref. 70.)... 

Nicotinic acid is pyridine-3-carboxylic acid and can be determined by direct titration with carbonate-free 0-lN sodium hydroxide using phenol red or phenolphthalein as indicator. 1 ml 0-1N = 0-01231 g. 

Although the B.P. directs that the nicotinic acid should be extracted with hot neutral ethanol and the extract diluted with water and titrated, this procedure is not necessary for tablets with normal excipients and a direct titration on the powdered tablets with 0-lN alkali to phenol red is satisfactory. 1 ml O IN 0 01231 g CgH OgN. 

Nikethamide, C10H14ON2, Mol. Wt. 178-2, is the diethylamide of nicotinic acid. Acid hydrolysis is necessary to hydrolyse this compound and for assay it is necessary to hydrolyse about 0-3 g with 50 per cent sulphuric acid for two hours before distilling the liberated diethylamine in the presence of excess of sodium hydroxide into standard acid and titrating the excess acid using methyl red as indicator. 1 ml 0-1N = 0-01782 g. 

Various esters e.g. benzyl, ethyl and phenyl) of nicotinic acid are met with in pharmaceutical products and they can be determined in ointments by non-aqueous titration after extraction from the basis. 

The indirect determination of certain organic substances can be made by complexometric titration methods. Such methods depend on the formation of an insoluble product between the organic material and a metal then, either the excess metal in solution is determined by a suitable titration with EDTA, or the metal-containing precipitate is decomposed and the liberated metal ions titrated. Thus, for example, narcotine, papaverine, codeine, strychnine and brucine have been determined by formation of iodobis-muthate complexes, chlorpromazine and quinine" as cadmium iodide complexes, purines and nicotinic acid derivatives by precipitation with mercury and barbiturates by precipitation with zinc. ... 

Titrations of many diprotic acids or bases show two clear end points, as in curve a in Figure 11 -4. Some titrations do not show both end points, as illustrated by curve b, which is calculated for the titration of 10.0 mL of 0.100 M nicotine (p/fbl = 6.15, pKbl = 10.85) with 0.100 M HC1. The two reactions are... 

In the first of these methods, a quantity of ground dry material (20-50 g.) is mixed with 10-30 cc. of a 40% solution of sodium hydroxide and extracted with ether in a Soxhlet. Aqueous alcohol is added to the extract, the ammonia removed by aeration, and the residual liquid titrated with O.lOiV acid in the presence of a lacmoid indicator to obtain the total alkaloid content. The neutral liquor is then extracted twice with dilute sulfuric acid. The combined acid extract is used for the determination of the alkaloids. A portion is treated with nitrous acid, almost neutralized, and poured into aqueous picric acid. The dipicrate of nicotine is thus obtained. After removal of nicotine dipicrate, the secondary bases are recovered, converted to the picrates and methylated. The nicotine dipicrate obtained by fractional crystallization corresponds to nornicotine (280). 

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