Erythromycin taste

The acid-instabihty of erythromycin makes it susceptible to degradation in the stomach to intramolecular cyclization products lacking antimicrobial activity. Relatively water-insoluble, acid-stable salts, esters, and/or formulations have therefore been employed to protect erythromycin during passage through the stomach, to increase oral bioavakabihty, and to decrease the variabiUty of oral absorption. These various derivatives and formulations also mask the very bitter taste of macroHdes. 

IMATINIB 1. ANTIBIOTICS - clarithromycin, erythromycin 2. ANTIFUNGALS -fluconazole, itraconazole, ketoconazole voriconazole 3. ANTIVIRALS -efavirenz, ritonavir 4. GRAPEFRUIT JUICE 5. H2 RECEPTOR BLOCKERS - cimetidine t imatinib levels with t risk of toxicity (e.g. abdominal pain, constipation, dyspnoea) and of neurotoxicity (e.g. taste disturbances, dizziness, headache, paraesthesia, peripheral neuropathy) Due to inhibition of CYP3A4-mediated metabolism of imatinib Monitor for clinical efficacy and for the signs of toxicity listed, along with convulsions, confusion and signs of oedema (including pulmonary oedema). Monitor electrolytes and liver function, and for cardiotoxicity... 

Taste acceptability is a particular issue with oral liquid dosage forms, lozenges, and chewable tablets. The problem may be overcome by the preparation of poorly soluble salts. Thus the bitterness of erythromycin and of bacitracin may be ameliorated by use of the estolate (lauryl sulfate) and zinc salts, respectively. Propoxaphene may be taste masked by forming the napsylate, the solubility of which may be further reduced and the taste improved by adding a common-ion salt such as sodium or calcium napsylate. 

Erythromycin estolate differs from other forms of erythromycin in that it is extremely stable to acid hydrolysis.5 Erythromycin liberated from the ester by mild alkaline hydrolysis is subject to rapid decomposition in strongly acid solutions. Kavanagh has stated that deterioration of erythromycin increases with an increase in temperature and decreases with an increase in pH up to 8.0. Buffered aqueous solutions of erythromycin base are quite stable at this pH. Acetone solutions of the ester form are stable, while acetone solutions of the propionyl erythromycin lauryl sulfate preparation are not. Powders and dry formulations are stable for at least five years. Liquid preparations become unacceptable after 2 years due to undesirable taste. 

Oral drugs with a markedly bitter taste may lead to poor patient compliance if administered as a solution or syrup. The prodrug approach has been used to improve the taste of chloramphenicol (20), clindamycin, erythromycin, and metronidazole.19 A prodrug such as chloramphenicol palmitate (21), with LogP of around 10, does not dissolve in an appreciable amount in the mouth and, therefore, does not interact with the taste receptors. 

Erythromycin ethyl succinate is a mixed double ester pro-drug in which one carboxyl of succinic acid esterifies the C-2 hydroxyl of erythromycin and the other ethanol (Fig. 38.28). This pro-drug frequently is used in an oral suspension for pediatric use largely to mask the bitter taste of the drug. Film-coated tablets also are used to deal with this. Some cholestatic jaundice is associated with the use of EES. 

Esters of the 3-carboxylic acid group of ampicillin (Section 13.1) are used as pro-drugs, e.g. bacampicillin, talampicillin, and pivampicillin. Their more lipophilic properties ensure better oral absorption. The active drug is liberated by the non-specific esterases of the bloodstream. Esters of erythromycin 4.47)., such as the stearate or ethyl succinate, survive the stomach s acidity, which erythromycin does not, but are hydrolysed back to the true drug in the duodenum. Children, who intensely dislike the bitter taste of chloramphenicol, are given the succinate ester. In both cases, hydrolysis liberates the true drug. 

Esters have also been used in a number of instances to mask unpleasant tastes. Examples include chloramphenicol palmitate, dindamydn palmitate and erythromycin ethyl succinate where in each case the free dmg tastes extremely unpleasant but its estetified form is tasteless. 

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