Codeine solubility

From what we see on the next page (properties) we can tell that codeine is not very soluble, so it stands to reason that this will be the last substance that will be eluted from the column. Acetaminophen looks the most soluble, so lets get rid of it first. Acetone looks like a good choice, but its hard to tell because the Merck Index did not say if the other substances are soluble or insoluble in acetone. Try a little and see what types of crystals appear upon evaporating off the solvent, test the melting point and see if it is exactly as stated for acetaminophen. If there are only two types of crystals then it may be easier to go ahead and elute these and then separate... 

Soaking plants parts in alcohol (ethanol) creates a tincture. In this process, pharmacologically active constituents of the plant are extracted by the alcohol. Tinctures do not contain the complete spectrum of substances that exist in the plant or crude drug, only those that are soluble in alcohol. In the case of opium tincture, these ingredients are alkaloids (i.e., basic substances of plant origin) including morphine, codeine, narcotine = noscapine, papaverine, narceine, and others. 

Nabitan (39) is a cannabis-inspired analgesic whose nitrogen atom was introduced in order to improve water solubility and perhaps to affect the pharmacological profile as well. The phenolic hydroxyl of benzopyran synthon is esterified with 4-(l-piperidino)butyric acid under the influence of dicyclohexyl carbodi mi de. In addition to being hypotensive and sedative-hypnotic, nabitran (39) is a more potent analgesic than codeine. The preparation of synthon begins with aceto-... 

Codeine, also known as methylmorpliine, C H2 NOt H20, is a colorless white crystalline substance, mp 154.9 C, slightly soluble in water, soluble in alcohol and chloroform, effloresces slowly in dry air. Codeine is derived from opium by extraction or by the methylation of morphine. For medical use, codeine is usually offered as the dichlotide, phosphate, or sulfate. Codeine is habit forming. Codeine is known to exacerbate urticaria (familiarly known as hives). Since codeine is incorporated in numerous prescription medicines for headache, heartburn, fatigue, coughing, and relief of aches and pains, persons with a history of urticaria should make this fact known to their physician. Codeine is sometimes used ill cases of acute pericarditis to relieve severe chest pains in early phases of disease. Codeine is sometimes used in drug therapy of renal (kidney) diseases. 

Opium alkaloids such as codeine, thebaine, papaverine, and noscapine exhibit high solubility (0.09-0.9 mg/g) in supercritical fluids including CO N,0, CHF, [37]. However, in spite of their high solubilities, they were not extracted from plant material by pure CO, to the degree expected [29], possibly because these alkaloids exist as their salt forms in plant tissue. In this chapter, the examples that show the difference of the solubilities between alkaloidal free bases and salts are presented. For this comparison, the solubilities of the free bases of hyoscyamine (1), scopolamine (2), pseudoephedrine (6) were measured and compared with those of their hydrochloride salts (Figures 3 and 4). 

Rapaport and Solyanik (168) have developed a rapid method of refractometric determination of 23 mixtures containing anesthesin, barbamyl, bromcamphor, bro-misoval, camphor, antipyrine, amidopyrine, acetalsali-cylic acid, barbital, codeine, salol, terpin hydrate, hexamethylenetetramine, and phenobarbital. The method described is suitable for analysis of pharmaceutical mixtures containing compounds which are insoluble in water and soluble in ethanol. A mixture of 2 pharmaceuticals (0.1 g) is dissolved in 1 ml. ethanol and np of this solution is determined. One component is... 

In the process of preparing a tincture, some pharmacologically active constituents of the plant are extracted by the alcohol. Although not all substances are soluble in alcohol, those that are include the alkaloids. In the case of a tincture of raw opium, the soluble alkaloids include morphine, codeine, noscapine, and papavarine. Such tinctures of opium were the infamous laudanum preparations of the late 1800s (see Appendix). 

In the same way, organic bases such as amines can be dissolved by lowering the pH. Codeine (7,8-didehydro-4,5-epoxy-3-methoxy-17-methylmorphinan-6-ol) is a commonly used painkiller. Codeine itself is not very soluble in water but it does contain a basic nitrogen atom that can be proto-nated to give a more soluble salt. It is usually encountered as a phosphate salt. The structure is com-... 

C7H4O C]4H802 95. a. 303 9 g/mol b. No, codeine could not be eliminated since its molar mass is in the possible range including the uncertainty c. We would like the uncertainty to be 1 g/mol. We need the freezing-point depression to be about 10 times what it was in this problem. Two possibilities are (1) make the solution ten times more concentrated (may be solubility problem) or (2) use a solvent with a larger Kf value, e.g., camphor. 

Cobeine is the methyl-phenyl ether with the hydroxyl hydrogen in position 3 replaced by methyl. Both morphine and codeine are crystalline compounds reacting as tertiary mono-acid bases. Morphine is slightly soluble in water, codeine being more so, the former being more bitter in taste than the latter. The salts are soluble and in this form the alkaloids are used in medicine though codeine is also used as the free base. 

Morphine was first isolated as a pure substance about 1814 and its composition determined in 1831. The isolation of morphine and codeine is similar to that of quinine, by extracting the opium with warm water and then treating the extract with lime. The two are then separated by the different solubility of the free bases. 

Aspirin BP In fine powder form for preparation of Soluble Aspirin Tablets and Soluble Aspirin, Phenacetin and Codeine Tablets... 

It iK dirs as levorotatory. colorless, efflorescent crystals orasawhitc crystalline powder. It is light sensitive. Codeine U slightly soluble in water (1 120) and sparingly soluble in ether (1 50). It is freely soluble in alcohol (1 2) and very soluble in chloroform (1 0.5). Codeine is a monoacidic base and readily forms salts with acids, with the most important being the sulfate and the phosphate. The acetate and methyl-bntniide derivatives have been used to a limited extent in tough preparations. 

Codeine Sulfate, USP. Ctxleine sulfate is prepared by neutralizing an aqueous suspension of codeine with diluted sulfuric acid and then effecting crystallization. It cK Curs us white cry.stals. usually needle-like, or as a white cry.stalline powder. The salt is efflorescent and light sensitive. It is. soluble in water (1 30. 1 6.S at 80°). much less soluble in alcohol (1 1.280). and insoluble in ether or chloroform. This salt of codeine is prescribed frequently but is not as suitable os the pho.sphate for liquid preparations. Solutions of the sulfate and the phosphate are incompatible with alkaloidal reagents and alkaline sub.stances. 

Dihydrocodeine Bitartrate. Dihydrocodcine is ob-kiincd by the reduction of codeine. The bitaitrate salt occurs as white cry.stals that are soluble in water (1 4.5) and only slightly. soluble in alcohol. Subcutaneously, a dose of 30 mg of this drug is almost equivalent to 10 mg of morphine assn analgesic, with 1 a.ster oreset and negligible side effects. It has addiction liability. It is available in combination with aspirin or acetaminophen fur pain. 

Carbetapentane Citrate. Carhetapentane citrate. 2- 2-idiothylamino)-ethoxy ethyl l-phcnylcyclopcntanecarbox-clate citrate, is a white, odorless crystalline powder that is fiecly soluble in water (1 1). slightly soluble in alcohol, and insoluble in ether. It is reportedly equivalent to codeine as at antitussive. Introduced in 1956, it is well tolerated and has... 

Addition of dilute hydrochloric acid will ionise the codeine and form codeine hydrochloride. This salt will be water soluble and will partition into the aqueous (lower) phase. Removal of the aqueous phase and addition of fresh organic solvent and a strong base (such as sodium hydroxide) will liberate codeine base in the organic phase. Evaporation of the volatile solvent yields pure codeine. 

In general, drug metabolism serves to inactivate a substrate and increase water solubility of the substrate for excretion, bioactivate a substrate or prodrug (e.g., codeine and cyclophosphamide) to an active or mutagenic principle, or less commonly, extend the elimination half-life of a pharmacologically active or potentially toxic metabohte. Metabolic reactions are often divided into Phase I and Phase II categories, as depicted in Figure 43-1. 

---