Controlled release medicament beadlet formulation - comprising non-lipophilic, non-fat binder and carboxylic acid to impart hardness and reduce particle size distribution

摘要

Formulation comprises a beadlet comprising: (a) 3-60 wt.% medicament(s) (I); (b) 5-50 wt.% carboxylic acid (II) to facilitate spheronisation, to impart hardness to the beadlet and aid in obtaining a desired narrow particle size distribution; and (c) a non-lipophilic, non-fat binder. (II) is malic, tartaric, maleic, fumaric, succinic or esp. citric acid. The ACE inhibitor is a substd. proline deriv., an ether or thioether mercaptoacyl proline, a carboxyalkyl dipeptide deriv., a phosphinylalkanoyl proline deriv., a phosphonamidate deriv., a phosphonate deriv. or a prolyl-amino acid deriv. The beta-blocker is used alone or together with a calcium channel blocker. Esp. the beta-blocker is nadolol, propanolol or atenolol and the calcium channel blocker is diltiazem, nifedipine, verapamil or trapamil. The calcium channel blockers above may also be used alone or together with an ACE inhibitor. A prefd. combination is captopril and diltiazem. The ACE inhibitor may be used together with a diuretic, esp. hydrochlorothiazide. The binder is pref. microcrystalline cellulose or a hydrocolloid, pref. a cellulose ether, esp. hydroxypropylmethyl cellulose.