Relationship between quality and serum level after the oral administration of commercial erythromycin tablets in man (author's transl)

Abstract

Disintegration of erythromycin tablets was compared by the disintegration test method in Japanese Pharmacopoeiae VIII and by the Erweka Disintegration Tester, using commercial erythromycin tablets (200 mg/tablet) manufactured by 16 firms and marketed in Japan during June to September, 1975. From the result of these tests, four kinds of tablets that required the longest time for disintegration and a kind of standard tablet that required the shortest time were selected. These tablets were alloted to 20 female subjects at a time (making a total of 100 test subjects) by the Latin square design method. The subjects took the tablets before breakfast and serum level of erythromycin was measured by the bioassay method 2, 4, 6, 9, and 12 hr later to examine bioavailability in humans. According to its result, two of these five products were bioinequivalent and, especially, one of them showed a maximum serum level and AUC of only 4% and 3.8%, respectively, of the values obtained from the product giving the highest values. In order to find the reason for such bioinequivalence and to detect such a product, dissolution rate of these tablets was examined by four methods ; J.P. VIII, U.S. Pharmacopoeia XIX, Sartorius SS, and Erweka Tester. It was thereby found that one of the bioinequivalent products did not undergo disintegation or dissolution in a solution of below pH 6.5, and this was thought to be the reason for its poor absorption from the digestive tract. In the other product, dissolution at pH 5.0-5.5 seemed to be related to the serum level of the ingredient but this point requires further examinations.