Pulsatile once-a-day delivery systems for minocycline

An improved pharmaceutical delivery system adapted to provide a therapeutically effective blood concentration level of 7-dimethylamino-6-deoxy-6-demethyltetracycline or a non-toxic acid addition salt thereof for a sustained period of time of up to about twenty-four hours comprising:

• (A) from 51 to 80 parts by weight per 100 parts by weight of (A) and (B) combined of an initial loading therapeutically effective number of quick release granules which comprise
• (a) (i) an effective amount of at least one pharmaceutically acceptable excipient;
• and
• (ii) an effective antibacterial amount of 7-dimethylamino-6-deoxy-6-demethyltetracycline or a non-toxic acid addition salt thereof, on or in said quick release granules;
• said quick release granules being adapted to release substantially completely said tetracycline or salt thereof in a medium having a pH of less than about 3.9;
• and
• (B) from 20 to 49 parts by weight per 100 parts by weight of (A) and (B) combined of a secondary loading therapeutically effective number of blended polymer coated spherical granules which comprise
• (a) (i) an independent effective amount of at least one pharmaceutically acceptable excipient which may be the same as or different than (A)(a)(i);
• and
• (ii) an independent effective antibacterial amount of 7-dimethylamino-6-deoxy-6-demethyltetracycline or a non-toxic acid addition salt thereof, on or in said coated spherical granules;
• and
• (b) a substantially uniform pH sensitive coating comprising a blend of at least two polymers on said coated spherical granules (B) one of which is non pH-sensitive and rapidly erodible in water and the other of which is pH-sensitive and erodible in a medium having a pH in the range of from about 4.5 to about 6.5;
• said coated spherical granules thereby being adapted to release some of said tetracycline or salt thereof in a medium having a pH in the range of from about 1.0 to about 3.0 and the remainder rapidly in a medium having a pH in the range of from about 4.5 to about 6.5.