Erythromycin formulations

Topical erythromycin formulations include a gel, lotion, solution, and disposable pads that are usually applied twice daily. 

Erythromycin formulations are highly irritant if administered by i.m. injection and are not used in horses. Many p.o. preparations of erythromycin are enteric coated to allow passage into the small intestine, where absorption is higher because of the higher pH. In horses, erythromycin stearate and erythromycin phosphate produce peak plasma concentrations faster than the ester formulations following p.o. administration. 

The ester and ester salts of erythromycin are variably absorbed (18-45%) from the small intestine into the systemic circulation. Overall, erythromycin bioavailability depends upon the formulation administered with greatest bioavailability observed with the esto-late salt (Ilosone brand) and the least is observed with the base formulation. The bioavailability of the ethylsuccinate salt is highly variable. The majority of erythromycin formulations are more completely absorbed when administered in the fasting state whereas the ethylsuccinate salt is better absorbed... 

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. 

Exchanges between pharmacopoeias are co-ordinated by the Pharmacopoeial Discussion Group (PDG) (International Harmonisation 1995) and it is frequent that one pharmacopoeia participates in a collaborative study organized by another pharmacopoeia, or that several pharmacopoeias share the same batch of reference substance to be used in their respective monographs nevertheless, in this case the reference substance can not be considered as harmonized. A new batch of erythromycin was shared between the United States Pharmacopoeia and the European Pharmacopoeia and was established in a common coEaborative study both for the microbiological assay (used in the USP for formulations) and the liquid chromatographic assay (used in the Ph. Eur. and USP for bulk material). 

Clindamycin 1% and erythromycin 2% preparations, applied once or twice daily, have similar effects and are the most commonly prescribed topical antibacterial agents.17 These agents, as well as sodium sulfacetamide, are available in various formulations for the treatment of acne. 

The complete degradation of sulfamethoxazole was also reported within 14 days with P. chrysosporium, Bjerkandera sp. R1 and B. adusta [4], although, contrary to the reports of enzymatic transformation, metabolites were not identified. Partial removal (from 30% to 55%) of sulfamethoxazole from activated-sludge-mixed liquor and the effluent of a WWTP was demonstrated at bench scale within 5 days with P. chrysosporium propagules entrapped in a granular bioplastic formulation [25]. This approach was also successful in the partial elimination of other kinds of antibiotics, eg., ciprofloxacin (see below) and the macrolide erythromycin. 

Erythromycin P. chrysosporium Inoculation of granular bioplastic formulation entrapping propagules of P. chrysosporium in wastewater 10 pg mL-1 98% after 30 days. [25]... 

Bulk erythromycin raw material is treated the same as the standard. Formulations are made up to the same concentration as the standard in methanol and buffer and 10 ml. aliquots used for chromophore development. 

The U. S. Dispensatory26 reports maximum serum levels of 0.2 ijg./ml. 1 hour after administration of a 250 mg. dose, 0.6 (ig./ml. 2 hours after a 500 mg. dose, and 1.2 ug./ml. 2 hours after a 1 g. dose. Higher blood levels are achieved on a multiple dosage schedule. Since it is acid labile, a resistant coating is used in tablet formulations to overcome the deleterious effect of gastric fluid on erythromycin base or the stearate salt is prepared which does not dissolve readily in the stomach. 

Specialized antibiotic formulations have been developed for DCT, with physicochemical properties chosen to confer prolonged retention in the mammary secretions (21,, ). Ziv ( ) has summarized the desirable kinetic and other properties of such a product. The following antibiotic formulations are presently approved by the U.S. Center for Veterinary Medicine, FDA for infusion into the dry mammary gland erythromycin (300 mg), oxytetracycline-HCl (426 mg), benzathine cloxacillin (500 mg), cephapirin benzathine (300 mg), novobiocin (400 penicillin (200,000 lU) novobiocin (400 mg), penicil-... 

Cholestatic hepatitis may occur when drug therapy lasts longer than 10 days or repeated courses are prescribed. The hepatitis is characterized by fever, enlarged and tender liver, hyperbilirubinemia, dark urine, eosinophilia, elevated serum bilirubin, and elevated transaminase levels. Hepatitis has been associated with the estolate salt of erythromycin but not with other formulations. Although the hepatitis usually occurs 10 to 20 days after the initiation of therapy, it can occur within hours in a patient who has had such a reaction in the past. The hepatitis is believed to be the result of both a hepatotoxic effect and a hypersensitivity reaction this latter effect is reversible on withdrawal of the drug. Erythromycin and derivatives induce hepatic microsomal enzymes and interfere with the actions of various drugs, including theophylline and carbamazepine. 

A 500-mg dose of clarithromycin produces serum concentrations of 2-3 mcg/mL. The longer half-life of clarithromycin (6 hours) compared with erythromycin permits twice-daily dosing. The recommended dosage is 250-500 mg twice daily or 1000 mg of the extended release formulation once daily. Clarithromycin penetrates most tissues well, with concentrations equal to or exceeding serum concentrations. 

To decrease the likelihood of irritation, application should be limited to a low concentration (2.5%) once daily for the first week of therapy and increased in frequency and strength if the preparation is well tolerated. Fixed-combination formulations of 5% benzoyl peroxide with 3% erythromycin base (Benzamycin) or 1% clindamycin (BenzaClin) appear to be more effective than individual agents alone. 

Erythromycin estolate is usually not recommended for adults because of the increased risk of cholestatic hepatitis. In children, however, this derivative rarely causes hepatitis, and some pediatric specialists prefer this formulation because of better availabihty. 

Examples of commercial enteric-coated formulations include Ery-Tab (erythromycin Abbott), Prilosec (omeprazole Astra Merck), Pancrease ... 

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