Abstract

A pharmaceutical oral controlled release multiple-units formulation in which individual units comprise cross-sectionally substantially homogeneous cores containing particles of a sparingly soluble active substance, the cores being coated with a coating which is substantially resistant to gastric conditions, but which is erodable under the conditions prevailing in the small intestine, in particular an enteric coating which is substantially insoluble at a pH below 7 such as Eudragit.RTM. S (an anionic polymerizate of methacrylic acid and methacrylic acid methyl ester), is prepared by a process comprising comminuting an active substance together with a substance which is readily soluble in intestinal fluids such as an anionic detergent to obtain particles containing the active substance in intimate admixture with the readily soluble substance, combining the resulting particles into cross-sectionally substantially homogeneous cores together with components which accelerate the disintegration of the cores and intestinal fluids such as talc and saccharose, coating the individual cores with an erodable coating, and combining a multiplicity of the coated cores into a capsule or tablet formulation.Such a coating may also be used when the active substance is a substance which exerts an irritating effect on the gastric mucosa and/or is unstable in an acidic environment.

Other References

• Yamanouchi, C.A., 94, #127362r (1981)
• Hazler, C.A., 91, #181467e (1979)
• Martin, C.A., 93, #245473e (1980)
• Elgindy, C.A., 96:11599k (1982)
• Lindberg, C.A., 77, #66167f (1972)
• Porebski, C.A., 75, #25335z (1971)
• Borzunov, C.A., 75, #121361a (1971)
• Biosrame, C.A., 97, #44255u (1982)
• Toyo, C.A., 97, #44326t (1982)
• Bogentoft, C.A., 96, #57792n (1982)
• Dreher, C.A., 94, #109115h (1981)
• Biosrame, C.A., 91, #181383z (1979)
• Lehmann, C.A., 91, #9441f (1979)
• El-Sayed, C.A., 89, #204156v (1978)
• Lehmann, C.A., 84, #95546d (1976)
• Lehmann, C.A., 81, #111411b, #68497v, #964404f (1974)
• Dittgen, C.A., 85, #198123p (1976)
• Kach, C.A., 86, #60497c (1977)
• Dittgen, C.A., 87, #11555g, (1977)
• Dittgen C.A. 87 #189376n (1977)
• Baggensen, S. et al (1981) Pharm. Acta Helv., 56, 85-92
• Bechgaard et al (1978) Drug Develop. Ind. Pharm. 4, 53-67
• Bechgaard et al (1978) J. Pharm. Pharmacol., 30, 690-692
• Bechgaard et al (1980) J. Pharma. Sci., 69, 1327-1330
• Bogentoft, et al (1978) Eur. J. Clin. Pharmacol., 14, 351-355
• Green, DM (1966) J. New Drugs, 6, 294-303
• McDonald et al (1977) J. Clin. Pharmacol., 17, 601-606
• Snedecor et al (1967) Iowa State University Press, Iowa, 271-275