Basic drug

The Bronsted-Lowry definition of a base is an acceptor of protons. Pharmaceutical and biological sciences are concerned mainly with the behaviour of drugs in aqueous systems. Under these conditions, drugs will behave as bases only if they contain a nitrogen atom with a lone pair of electrons available for reaction with protons. The major class of compound to work in this way is the amines. An amine in aqueous solution will react with water to release hydroxide ions (OH-) as shown in equation (3.4). 

Water donates the proton and functions as an acid in this reaction. The equilibrium constant for this reaction is defined as Kh and the greater the value of Kh the stronger will be the base. 

However, as was discussed in Chapter 1, most of the pharmaceutical literature refers to the strength of bases in terms of the pfCa of the conjugate acid of the base (R3NH+ above). In this case, the higher the value of pKa the stronger is the base. 

Basic drugs are usually administered as their water-soluble salts (generally the hydrochloride). Care must be taken not to co-administer anything that will raise the pH of the hydrochloride salt solution in case precipitation of the less water-soluble free base occurs. 

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Basic drugs human serum liq-liq extraction ion-pair C18 C18 UV 37... 

As patents expire, exclusivity of producing a trade-nemed product will pass and competitive-versions of the basic drug will be marketed under generic names (or other new trade nemes) by new manufacturers. It has been estimated that 40% of the drugs on the market in 1990 will be generic drugs. 

With regard to the resolution of enantiomers, some applications can be found with modified silica gel supports. Thus, a Pirkle-type CSP was used for the separation of 200 mg of a racemic benzodiazepinone [75]. Also tris-(3,5-dimethylphenyl)carba-mate of cellulose coated on silica [91, 92] was applied successfully to the resolution of the enantiomers of 2-phenoxypropionic acid and to oxprenolol, alprenolol, propranolol among other basic drugs. However, the low efficiency of this technique and the relative high price of the CSPs limits its use to the resolution of milligram range of sample. 

Lombardo F, Obach RS, Shalaeva MY and Gao F. Prediction of volume of distribution values in humans for neutral and basic drugs using physicochemical measurements and plasma protein binding data. J Med Chem 2002 45 2867-76. 

Avdeef, A., Artursson, P., NeuhofF, S., Lazorova, L., Grasjo, J., Tavelin, S. Caco-2 permeability of weakly basic drugs predicted with the double-sink PAM PA pKl method. Eur.J. Pharm. Sci. 2005, 24, 333-349. 

M. Y., Gao, F. Prediction of human volume of distribution values for neutral and basic drugs. 2. Extended data set and leave-class-out statistics. J. Med. Chem. 2004, 47,1242-1250. 

QSAR studies of the pH-dependent partitioning of acidic and basic drugs into liposomes [64] yielded following equations ... 

Schaper, K.-J., Zhang, H., Raevsky, 0. A. pH-dependent partitioning of acidic and basic drugs into liposomes - a quantitative structure-activity relationship. Quant. Struct.-Act. Relat. 2001, 20, 45-54. 

Reymond, F., Steyaert, G., Carrupt, P. A., Testa, B., Girault, H. H. 10. Mechanism of transfer of a basic drug across the water/l,2-dichloroethane interface the case of quinidine. Helv. Chim. Acta 1996, 79, 101-117. 

However, the half-wave transfer potential is not a constant when ionizable compounds are eoneerned, beeause their transfer behavior depends on their degree of disso-eiation and henee on the pH of the aqueous phase. For instance, with a basic drug B that can be protonated onee to give BH, it has been shown [230] that Agy-... 

Bovine serum albumin covalently bonded to silica and a-acid glycoprotein immobilized on silica have been used to resolve a wide range of acidic and basic drugs and amino acid derivatives [807-810]. Because of their complex structures, however, the... 

Applications APCI-MS is often more widely applicable than ESI-MS to the analysis of classes of compounds with a low molecular weight, such as basic drugs and their metabolites, antibiotics, steroids, oestrogens, benzodiazepines, pesticides, surfactants, and most other organic compounds amenable to El. LC-APCI-MS has been used to analyse PET extracts obtained by a disso-lution/precipitation procedure [147]. Other applications of hyphenated APCI mass spectrometric techniques are described elsewhere LC-APCI-MS (Section 7.33.2) and packed column SFC-APCI-MS (Section 73.2.2) for polar nonvolatile organics. 

By comparing gastric absorption at pH 3 and pH 6 where surface area and factors other than pH are constant, one sees that the general principle is supported acid drugs are more rapidly absorbed from acidic solution, whereas basic drugs are more rapidly absorbed from relatively alkaline solution. 

At the same pH (i.e., pH 6) acidic and basic drugs are more rapidly absorbed from the intestine compared to the stomach, by virtue of the larger intestinal surface area. 

If the solubility of a drug is to be reduced to enhance stability or to prepare a suspension, the for-mulator may prepare water-insoluble salts. A classic example is procaine penicillin G, the decreased solubility (7 mg/mL) of which, when compared with the very soluble penicillin G potassium, is utilized to prepare stable parenteral suspensions. Another alternative to preparing an insoluble drug is to use the parent acidic or basic drug and to buffer the pH of the suspension in the range of minimum solubility. 

Wagner, J. G. Sedman, A. J., Quantitation of rate of gastrointestinal and buccal absorption of acidic and basic drugs based on extraction theory, J. Pharmacokinet. Biopharm. 1, 23-50 (1973). 

II. DISSOLUTION OF ACIDIC AND BASIC DRUGS IN UNBUFFERED MEDIA... 

The convective diffusion approach for weak basic drugs dissolving in acidic media was previously derived by Litt and Serad [9] and, as shown by McNamara and Amidon, could be applied to dissolution of the free base of papaverine. 

The accelerated dissolution of soluble pure acidic or basic drugs, through the addition of acidic or basic components to the dissolution media, becomes significant when the concentration of added components approaches the intrinsic solubility of the drug. 

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