Biodegradable implants from poly-(alpha-hydroxy acid) polymers for isoniazid delivery.
METHODS
In vitro and in vivo study of an isoniazid (INH) drug delivery system.


OBJECTIVE
To develop a system for the treatment of tuberculosis using a subcutaneous polymer implant with a large drug load released slowly over a long period. INH delivery by biodegradable poly-(alpha-hydroxy acid) polymers was evaluated using ground polymer and compression molded implants.


METHODS
Rate of drug release and structural stability of the implant in an aqueous environment were measured, as were in vivo evaluations of the duration of measurable levels of INH in serum and urine.


RESULTS
Factors that influenced the suitability of an implant in an in vitro system included polymer molecular weight and crystallinity, polymer and drug particle size, drug loading dose, and press temperature and pressure. The implant characteristics that most closely approached optimal conditions include a polymer of 100% L-lactide with low intrinsic viscosity, polymer particle size <75 micron, and INH particle = 126-180 micron, INH loading dose not to exceed 46%, and press conditions of 70 degrees C and 345000 kPa. Studies of subcutaneous implants in rabbits and baboons show that INH is released from the implant for 15 to 26 weeks.


CONCLUSIONS
An INH-containing polymer was developed that was structurally stable in an aqueous environment and that released INH over a period of at least 15 weeks. Studies with infected animals will be necessary to determine the dose required for prophylaxis and treatment of active disease.
Hurley
L
L
West Side VA Medical Center and the University of Illinois College of Medicine, Chicago, USA.
Andersen
B R
BR
D000818:Animals; D000995:Antitubercular Agents / Q000008:administration & dosage*; D001673:Biodegradation, Environmental; D002850:Chromatography, Gel; D016503:Drug Delivery Systems; D007538:Isoniazid / Q000008:administration & dosage*; D010215:Papio; D010316:Particle Size; D011108:Polymers; D019736:Prostheses and Implants; D011817:Rabbits
D000995:Antitubercular Agents; D011108:Polymers; D007538:Isoniazid