SUSTAINED-RELEASE OF A DUAL ANTI-MALARIAL SYSTEM

The sustained release of a dual drug system in a biodegradable carrier was evaluated in rhesus monkeys and mice. The two drugs were sulphadiazine (WR‐7557) (3H‐labelled) and 2,4‐diamino‐6‐(2‐naphthylsulphonyl)quinazoIine (WR‐158122) (14C‐Iabelled). The carrier was a polymer of L‐lactide (90 parts by weight) and glycolide (10 parts), with a molecular weight of 46 000. The dual system injected was a blend of two preparations, each 50% (w/w) of the appropriate drug in the polymer, in a weight ratio of ten parts of the sulphadiazine system to one part of the WR‐158122 system. This blend, as cryogenically ground particles, was injected intramuscularly into three monkeys; a fourth monkey received an equivalent dose of a 10:1 mixture of the pure drugs. Excretion of radioactivity in urine and faeces was measured over 13 weeks. Similar studies were done with mice. In monkeys, 14C‐labelled material derived from WR‐158122 was excreted at a nearly uniform rate; expressed as WR‐158122, the rate of excretion from the pure drug mix was approximately 50 μg day−1 from week three to week 13, while the drug/polymer matrix released the drug at approximately 26 μg day−1 during this period. Recovery of tritiated materials derived from sulphadiazine was approximately 82% of the injected dose in the first three weeks and only a slight difference in release characteristics of the pure drug mix and the mixed drug/polymer matrices was observed. Results of studies with both mice and monkeys were generally consistent. 1979 Royal Pharmaceutical Society of Great Britain