Kunihito Saito

Addition of Sugar Fatty Acid Esters to Digoxin Suppository and Its Prolonged Action

Rectal suppositories of digoxin were prepared from cacao butter containing 5 % of polysorbate 60 and 1, 2, or 5 % of sucrose fatty acid esters with HLB value of approximately 11 and 15 (SFAE-11, SFAE-15). Physical properties such as melting point, dissolution time and hardness of these suppositories were determind. Blood samples of rabbits were collected at 0.5, 1.5, 3.0, 4.5, 7.0 and 9.0 hours after rectal administration of digoxin (0. 3mg/kg). The plasma digoxin levels were determined by a radioimmunoassay method. Long lasting effect for digoxin suppositories containing SFAE-11 and SFAE-15 was estimated from the relative areas under the concentration-time curve over 0 to 9 hours, and the ratios between 0.5 hour value and 1.5 hour value of plasma digoxin concentration-time curve for digoxin suppositories containing 1, 2, or 5 % of SFAE-15 were 1.52, 2.14 and 2.23, respectively. The ratios for the suppositories containing 1, 2, or 5 % of SFAE-11, as determined by Formula 1 as standard, were 0.67, 0.87, and 1.23, respectively. The ratios between 0.5 hour value for Formula 1 to 7 was 0.55, 0.54, 0.70, 0.89, 0.77, 0.91, and 0.94, respectively.

Identification of Coating Materials for Enteric Coated Preparations

Enteric coating substances were tested in terms of disintegration time of the preparations. The samples used are 8 brands of multiple digestive enzyme capsules containing enteric coated granules and 5 of enteric coated granules (2 anti-inflammatory enzyme preparations and 1 each preparation of an antipyretic, kallidinogenase and ATP). The dissolution test was also conducted on the digestive enzyme preparations. Although all the samples passed the disintegration test of J. P. IX, the disintegration time of all the samples delayed when pH of the test solution was less than 6.0. After detailed observation, the samples were classified into two groups: group 1 in which disintegration time delayed at 5.25 and stopped at pH 5.0, and group 2 in which the time delayed at pH 5.5 and stopped at pH 5.25. The delayings were also found in the dissolution profiles of active ingredients from the sample preparations. In the analysis of the enteric coating substances by infrared spectra, the substances in group 1 were identified with hydroxypropyl methyl cellulose phthalate and those in group 2 with cellulose acetate phthalate. It is concluded that enteric coating substances used in pharmaceutical preparations are identified by the disintegration time and infrared spectra.