Chlorpromazine solubility

The results of a pH 4-9.5 solubility assay of chlorpromazine are shown in Fig. 6.10. The horizontal line represents the upper limit of measurable solubility (e.g., 125 pg/mL), which can be set by the instrument according to the requirements of the assay. When the measured concentration reaches the line, the sample is completely dissolved, and solubility cannot be determined. This is automatically determined by the instrument, based on the calculated value of R. When measured points fall below the line, the concentration corresponds to the apparent solubility Sapp. 

Figure 6.10 High-throughput solubility-pH determination of chlorpromazine. The horizontal line indicates the set upper limit of solubility, where the compound completely dissolves and solubility cannot be specified. The points below the horizontal line are measured in the presence of precipitation and indicate solubility. The solubility pH curve was collected in the presence of 0.5 vol% DMSO, and is affected by the cosolvent (see text). [Avdeef, A., Cun Topics Med. Chem., 1, 277-351 (2001). Reproduced with permission from Bentham Science Publishers, Ltd.]...

An oral suspension of chlorpromazine has the following composition and must be extracted so that excipients are removed prior to analysis by UV spectrophotometry Chlorpromazine 0.025% w/v, parahydroxybenzoic acid methyl ester 0.1 % w/v, neutral water soluble dye, lipophilic flavouring agent, sodium lactate buffer. 

Chlorpromazine is practically insoluble in water, soluble to the degree of 1 part in 2 parts of alcohol, 1 part in less than 1 part of chloroform, and 1 part in 1 part of ether [4]. 

Once first-pass metabolism has occurred, metabolites are excreted into the bile and then the small bowel. Those that are lipid soluble are reabsorbed into the portal circulation, eventually entering the systemic circulation. These metabolites may have a similar or substantially different pharmacological profile from their parent drug. For example, chlorpromazine undergoes extensive hepatic biotransformation and has 168 theoretical metabolites, 70 of which have been identified in plasma and... 

Most substances have at least some degree of solubility in water and while they may appear to be insoluble by a qualitative test, their solubility can be measured and quoted precisely. In aqueous media at pff 10, chlorpromazine base has a solubility of 8 x 10 mol dm, that is it is very slightly soluble, but it might be considered to be insoluble if judged visually by the lack of disappearance of solid placed in a test-tube of water. 

For some time, we ve known that antibiotics like tetracycline and erythromycin destroy bowel bacteria and block vitamins K, Bj2, and other B vitamins produced by beneficial bowel bacteria. Antidepressants, such as imipramine, and antipsy-chotics, such as chlorpromazine, interfere with the B vitamin riboflavin. Seniors who take mineral oil as an aid to regularity are wiping out fat-soluble vitamins such as A, D, E, and K. 

The vast majority of salt forms are developed to enhance the aqueous solubihty of drug substances. In some cases, a salt may be preferred with reduced solubihty for use in suspension formulations where solubihty as low as possible is optimum to prevent Ostwald ripening, for taste masking or to prepare a sustained release product. Chlorpromazine is marketed as a tablet and syrup using the hydrochloride salt but the insoluble embonate salt is used in suspension formulations to extend the duration of achon and minimize taste problems. Occasionahy the selection of a salt with only modest aqueous solubihty may be more suitable for use in tablet products prepared by wet granulation. For example, prochlorperazine maleate is used in Stemehl tablets rather than the highly soluble mesylate salt. 

Much of the beneht in solubihty enhancement from salt formation is attributable to the change in solution pH caused by the presence of the counterion. This occurs because the ionization and solubility of acidic drugs (such as barbiturates and non-steroidal anti-inflammatory drugs) increases in basic conditions but decreases in acidic conditions. This behavior is exemplified by derivations of the Henderson-Hasselbalch equations (37.2) and (37.3). The opposite situation occurs for basic drugs such as chlorpromazine, morphine and codeine, which are more soluble in acidic conditions. 

Control of solubility Itraconazole/p-CD oral delivery form (improved solubility) glibomuride/p-CD testosterone (progesterone)/branched CD lotepredrol/a-CD (nasal delivery form) flufenamic acid/triacetyl-P-CD complex (limited solubility) hydrocortisone, digitoxin, diazepam, indomethacin, chlorpromazine. 

The phenothiazine bases can be set free horn acid solution with 5% sodium hydroxide solution and extracted with ether. Buffer solutions of pH 10 are better since, e. g., chlorpromazine decomposes already in normal alkali solutions [51]. It is imperative to use peroxide-free ether in order to avoid oxidation. The phenothiazine hydrochlorides may be extracted directly from hydrochloric acid solution with chloroform, in which they are easily soluble [46]. Since phenothiazines easily imdergo change in daylight or UV light, especially in acid solution [101, 150], they must be protected against this influence. 

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