Codeine formulations

Brand Ingredients other than codeine Formulation Use... 

Opium is the dried, powdered sap of the unripe seed pod of Papaver somniferum, a poppy plant indigenous to Asia minor. Theophrastus described its medical properties in the third century BC, but the Sumerians, ca BC 4000, probably perceived its utility. Arab physicians knew of the dmg, and Arab traders carried it to the Orient where it was used as a treatment for dysentery. Paracelsus is credited with repopularizing the dmg in western Europe in the early sixteenth century by formulating opium into "laudanum", which is still in use. More than 20 different alkaloids (qv) of two different classes comprise 25% of the weight of dry opium. The benzylisoquinolines, characterized by papaverine [58-74-2] (1.0%), a smooth muscle relaxant, and noscapine [128-62-1] (6.0%), an antitussive agent, do not have any analgesic effects. The phenanthrenes, the second group, are the more common and include 10% morphine (1, = R = H), 0.5% codeine [76-57-3], C gH2 N03, (1, R = H, R = CH3), and 0.2 thebaine [115-37-7], C 2H2 N03, (2). 

An MEKC method for the determination of ibuprofen, codeine phosphate hemihydrate, their nine potential degradation products, and impurities in a commercial tablet formulation was developed, optimized, and fully validated according to ICH guidelines and submitted to the regulatory authorities. The optimized system containing ACN as organic modifier allowed baseline separation of ibuprofen, codeine, and nine related substances within 12 min. 

Although codeine is manufactured in formulations in which it is the sole active ingredient (codeine phosphate oral... 

The opioid derivatives most commonly used as antitussives are dextromethorphan, codeine, levopropoxyphene, and noscapine (levopropoxyphene and noscapine are not available in the USA). They should be used with caution in patients taking monoamine oxidase inhibitors (see Table 31-5). Antitussive preparations usually also contain expectorants to thin and liquefy respiratory secretions. Importantly, due to increasing reports of death in young children taking dextromethorphan in formulations of over-the-counter "cold/cough" medications, its use in children less than 6 years of age has been banned by the FDA. Moreover, due to variations in the metabolism of codeine, its use for any purpose in young children is being reconsidered. 

Y. Shih, J.-M. Zen and H.-H. Yang, Determination of codeine in urine and drug formulations using a clay-modified screen-printed carbon electrode, J. Pharm. Biomed. Anal., 29 (2002) 827-833. 

Papaveretum is a mixture of purified opium alkaloids, as their hydrochlorides, and is now formulated to contain only morphine (85.5%), codeine (7.8%), and papaverine (6.7%). It is used for pain relief during operations. 

Codeine (Figure 31-1), oxycodone, dihydrocodeine, and hydrocodone are all somewhat less efficacious than morphine (they are partial agonists) or have adverse effects that limit the maximum tolerated dose when one attempts to achieve analgesia comparable to that of morphine. These compounds are rarely used alone but are combined in formulations containing aspirin or acetaminophen and other drugs. 

SCHEDULE II Certain barbiturates, cocaine, codeine, codeine + acetaminophen (depends on dose and formulation), fentanyl (depends on dose), hydrocodone, hydromorphone, meperidine, methadone, morphine (depends on combination with other pain relievers), oxycodone, propoxyphene... 

SCHEDULE V Codeine + acetaminophen (depends on dose and formulation)... 

Papaver somniferum (opium poppy) contains a variety of opioid and related alkaloids, including codeine, morphine, noscapine, papaverine, and thebaine. Crude opium is the air-dried latex obtained by incising the unripe capsules of P. somniferum. Paregoric is ammoniated tincture of opium (Scotch paregoric) or camphorated tincture of opium (English paregoric). The use of these formulations has largely been replaced by use of the purified compounds. 

Many examples of the effects of tablet excipients on dmg decompositions are reported in the pharmaceutical literature. Chemical interaction between components in solid dosage forms may lead to increased decomposition. Replacement of the phenacetin in compound codeine and ARC tablets by paracetamol in NHS formulations in Australia in the 1960s (because of the undesirable side-effects of phenacetin), led to an unexpected decreased stability of the tablets. The cause was later attributed to a transacetylation reaction between aspirin and paracetamol and also a possible direct hydrolysis of the paracetamol (Scheme 4.15). 

As for codeine, oxycodone is frequently formulated in combination with aspirin (Percodan) or acetaminophen (Percocet and Tylox). Therefore the detection of either salicylate or acetaminophen along with codeine or oxycodone in the urine of patients who display an opiate toxidrome should lead to the measurement of salicylate or acetaminophen in serum to assess their toxicity (see Salicylate and Acetaminophen sections). Alternatively, empiric quantitive serum acetaminophen and salicylate determinations are... 

The facts that the degradation of the morphine alkaloids to fully aromatic phenanthrene derivatives is always accompanied by loss of the whole of the basic side-chain, and that loss of the latter is never observed independently of formation of such an aromatic derivative, led Gulland and Robinson [1, 118] to perceive that the nitrogen-containing side-chain must be so located that its extrusion is a necessary part of aromatization. The only positions for the attachment of the carbon end of the side-chain on this assumption are C-13 and C-14 of the phenanthrene skeleton, and the formulae [cxi] for codeine and [cxn] for thebaine were accordingly advanced [1], later being modified to [cxm] and [oxiv] respectively [118]. Such formulations allow the construction of plausible mechanisms for the degradation of the morphine alkaloids to phenanthrene derivatives. 

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