Continued Development and Testing of a Sustained Release System for the Prevention of Malaria.
Abstract
The major effort has been the preparation and evaluation of a matrix for simultaneous delivery of tritiated sulfadiazine (WR-7557) and carbon-14 labeled 2,4-diamino-6-(2-naphthylsulfonyl)quinazoline (WR-158122). Fabrication involved blending of two matrices, each consisting of 50 w/w% of the appropriate drug, in a weight ratio of ten parts of the WR-7557 matrix to one part of the WR-158122 matrix. This blend (sample 27392-A) was injected intramuscularly into three Rhesus monkeys (macaca mulata). A fourth monkey, serving as a control, received an equivalent dose of a ten-to-one ratio of pure drugs. Carbon-14 labeled materials derived from WR-158122 were found to be excreted at a uniform rate from the pure drug mix at approximately 50 microgram/day from week three to week 13, and from the drug polymer matrix at an essentially zero order rate of approximately 2.6 microgram/day during this period. Comparison of sulfadiazine excretion with results of WR-7557 experiments with mice shows wide variation. Initial release (first two weeks) from rods, beads, and powders apparently depends on specific external surface area. Excretion of labeled materials were all low and about the same; on autopsy the rods and beads were shown to be encapsulated by a thin clear film, and although this was not apparent in the powdered samples, the low continuous release suggested its presence.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 03, 1977
- Accession Number
- ADA046360
Entities
People
- D. L. Wise
- Joseph D. Gresser