Design of a slow-release capsule using laser drilling.

Conventional hard gelatin capsules were made GI-tract resistant by formalin vapor treatment. The residual formalin content was 80 micrograms/capsule 24 h after treatment, which decreased with increased storage time. An in vitro GI-tract resistance test was performed by exposing the capsules to simulated gastric fluid for 4 h and then to simulated intestinal fluid for 4 h at 37 degrees C. The resistance was further confirmed by in vivo X-ray studies in human volunteers. Minute pores were drilled on the hardened shells of the capsules with a carbon dioxide gas laser. This permitted the slow passage of the encapsulated tetracycline hydrochloride when subjected to 0.1 M HCl in in vitro dissolution studies. In vitro drug release from these capsules followed zero-order kinetics after an initial lag period of 30 min. The factors influencing the in vitro release rate of tetracycline hydrochloride from these capsules are discussed.