Solid basic drugs

Ghen X-H, Franke J-P, Wijsbeek J, de Zeeuw RA. 1994. Determination of basic drugs extracted from biological matrices by means of solid-phase extraction and wide-bore capillary gas chromatography with nitrogen-phosphorus detection. 

Huang Z-P, Chen X-H, Wijsbeek J, Franke J-P, de Zeeuw RA. 1996. An enzymic digestion and solid-phase extraction procedure for the screening for acidic, neutral, and basic drugs in liver using gas chromatography for analysis. J Anal Toxicol 20 248. 

It is common practice in pharmaceutical industry to generate salt forms of a drug substance to improve solid-state properties and solubility. CE has proven its ability to analyze reliably organic acids (direct, indirect detection) and alkaline/earth alkaline metals and basic amino acids. For basic drugs, a non-toxic organic acid or inorganic acid is chosen as counterion. Acidic drug substances will usually be deprotonated by alkaline and earth alkaline... 

Mallet, C. R., Mazzeo, J. R., and Neue, U. (2001). Evaluation of several solid phase extraction liquid chromatography/tandem mass spectrometry on-line configurations for high-throughput analysis of acidic and basic drugs in rat plasma. Rapid Commun. Mass Spectrom. 15 1075-1083. 

V. Marko, L. Soltes, and I. Novak, Selective solid-phase extraction of basic drugs by Cl8-silica. Discussion of possible interactions, J. Pharm. Biomed. Anal., 5 297-301 (1990). 

E. Zannou, Q. Ji, A. Serajnddin, and Y. Joshi, Stabilization of maleate salt of a basic drug in solid dosage form by microenvrromental pH adjnstment. Inti. J. Pharmaceutics (Oct 2006), snbmitted. 

This chapter is divided into three sections. In Section 4.2, the two most relevant physicochemical properties for drug delivery, solubility and stability, are discussed. In addition to providing a basic understanding of the importance of solubility and stability to drug delivery, methods to enhance solubility and physical and chemical stability are described. Section 4.3 focuses on the processes required for the proper drug formulation. Since most drugs are administered in the solid state, the formulation process for tablets is described in detail. Finally, Section 4.4 discusses some of the basic drug delivery methods, with an emphasis on the physicochemical properties that impact those methods. 

Many synthetic substances to be used in solid dosage form are too limited in solubility to be therapeutically effective. The desirable solubility for an oral solid is suggested to be more than 1 mg/ml (0.1%). To increase solubility, a weak basic drug such as an amine may react with respective mineral acids to form salts, that is, hydrochloride (more than 40% of the salt marketed), sulfate, or phosphate. For an amine with two functional groups, a mono- or dihydrochloride salt may be formed, depending on the condition and amount of hydrochloric acid added. For an organic acid, a salt with sodium or potassium can easily be formed. Because a molecule of salt is polar, it should be freely soluble in water, reaching a therapeutic solubility level. The other types of acids commonly used for salt formation with a weak base are sulfonic acids and carboxylic acids. 

Mallet, C.R. Mazzeo, J.R. Neue, U. Evaluation of Several Solid Phase Extraction Liquid Chromatography/Tandem Mass Spectrometry On-line Configurations for High-throughput Analysis of Acidic and Basic Drugs in Rat Plasma," Rapid Commun. Mass Spectrom. 16,421 26 (2002). 

Marko, V, Soltes, L., and Radova, K. 1990. Polar interactions in solid-phase extraction of basic drugs by octadecylsilanized silica, J. Chromatog. Sci., 28 403-406. 

Ruane, R. J. and Wilson, I. D. 1987. The use of Cl 8 bonded silica in the solid-phase extraction of basic drugs—possible role for ionic interactions with residual silanols, J. Phamaceut. Biomed. Anal., 5 723-727. 

Logan, B. K., Stafford, D. T., Tebbett, I. R., and Moore, C. M. 1990. Rapid screening of 100 basic drugs and metabolites in urine using cation exchange solid-phase extraction and high-performance liquid chromatography with diode array detection, J. Anal. Toxicol., 14 154-159. 

Musch, G. and Massart, D. L. 1988. Isolation of basic drugs from plasma using solid-phase extraction with a cyanopropyl-bonded phase, 7. Chromatog., 432 209-222. 

Chen, X. H., Franke, J. P, Wijsbeek, J., and de Zeeuw, R. A. 1992. Isolation of acidic, neutral, and basic drugs from whole blood using a single mixed-mode solid-phase extraction column, J. Anal. Toxicol., 16 351-355. 

Whelpton, R. Hurst, P.R. Metcalfe, R.F. Saunders, S.A. Liquid chromatographic determination of hy-oscine (scopolamine) in urine using solid phase extraction. Biomed.Chromatogr, 1992, 6, 198-204 Achari, R.G. Jacob, J.T. A study of the retention behavior of some basic drug substances by ion-pair HPLC. J.Liq.Chromatogr., 1980, 3, 81-92 [also N-acetylprocainamide, antazoline, atropine, caffeine, chlorpheniramine, codeine, ephedrine, epinephrine, naphazoline, papaverine, pheniramine, phenylephrine, phenylpropanolamine, procainamide, quinidine, xylocaine]... 

Lombardo F, Obach RS, Shalaeva MY and Gao F, Prediction of human volume of distribution values for neutral and basic drugs. 2. Extended data set and leave-class-out statistics, /. Med. Chem., 47, 1242-50 (2004). Ref. 299 = Hogberg T, Ramsby S, de Paulis T, Stensland B, Csorre I and Wagner A, Solid state conformations and antidopaminergic effects of remoxipride hydrochloride and a closely related salicylamide, FLA797, in relation to dopamine receptor models. Mol. Pharmacol., 30, 345-351 (1986). 

Fan, Y. Feng, Y. Da, S. Shi, Z. Poly(methacrylic acid-ethylene glycol dimethacrylate) monolithic capillary for in-tube solid phase microextraction coupled to high performance liquid chromatography and its application to determination of basic drugs in human serum. Analyriica Chimica Acta 2004, 523, 251-258. 

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