Erythromycin acistrate

Riippi, M., Antikainen, O., Niskanen,T., and Yliruusi, J. (1998),The effect of compression force on surface structure, crushing strength, friability, and disintegration time of erythromycin acistrate tablets, Eur. J. Pharm. Biopharm., 46, 339-345. 

Non-contact laser profilometry has been used to obtain roughness parameters and surface fractal dimension (Ds) of erythromycin acistrate tablets It was expected that tablet surface fractal dimension (Ds) will depend on the compression force used for tabletting. However, tablet surface fractal dimension was found independent of the compression force ranging from 4 to 22 kN. Instead, a surface roughness parameter Rp, which is the maximum distance between the highest point and the average height of the surface profile, indicated the variation of tablet friability as a function of compression force (Fig. 7). 

Ester derivatives of erythromycin, shown in Table 4, were synthesized soon after its discovery (124—126). They are readily prepared by acylation of the 2-hydroxyl group the neighboring 3r-dimethylamino group directs acylation to this site. Commonly used esters of erythromycin are propionate, acetate, ethyl succinate, and ethyl carbonate (30). 2r-Esters do not bind bacterial ribosomes, however, and consequently must be hydrolyzed back to the parent to exert antibacterial activity (127). Ester derivatives are still being prepared (128,129). 2,-0-Acetylerythromycin stearate, also known as erythromycin acistrate, is an example undergoing clinical trial (11,130,131). Two salts of 2,-0-propionyl-erythromycin, N-acetylcysteinate (erythromycin stinoprate) and mercaptosuccinate, were prepared to combine antibiotic and mucolytic properties in a single agent (132—134). 

Combinations of a 2 -ester and a lipophilic acid-addition salt have also been extensively employed. Erythromycin estolate (2 -propionate, lauryl sulphate salt) has been widely used due to its better oral absorption than other forms of erythromycin [62, 67, 68]. Similar results have been found with erythromycin acistrate (2 -acetate, stearate salt) [69, 70], which is reported to be less hepatotoxic in animals than other forms of erythromycin [71], Two salts of 2 -propionylerythromycin,A-acetyIcysteinate (erythromycin stinoprate) and mercaptosuccinate, are being investigated as combinations of an antimicrobial and mucolytic agent [72-74],... 

Erythromycin exhibits low oral bioavailability, low serum concentrations, a short in vivo half-life, and a high degree of intra- and inter-subject variability. Crystalline forms of erythromycin were found to be more bioavailable than amorphous forms [245]. TTie bioavailabilities of dirithro-mycin and erythromycin acistrate are increased by adding a basic substance such as a carbonate salt to the tablet or capsule [246, 247]. 

Ac, octadecanoate salt Erythromycin acistrate, INN. Erasis. Gallimycin iV. Matachron [96128-89-1]... 

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