• Elucidation of the nature of the plug formation process and its implications in a dosing disk machine using an instrumented Hofliger Karg GKF 330 capsule filling machine

      Cropp, John Worth; Augsburger, Larry L. (1992)
      Particle deformation, stress transmission, and bonding in compacts have been studied extensively at higher force levels such as those associated with tableting equipment. However, fundamental questions exist regarding the nature of particle behavior during compaction at low forces, such as seen with the dosator and dosing-disk type automatic capsule filling machines. There are published reports in the literature citing unusual dissolution behavior of finished capsule dosage forms for which no explanation is available. An Hofliger Karg GKF 330, a dosing-disk machine, previously instrumented to monitor tamping force, was further modified to allow for simultaneous monitoring of brass ring movement and movement of individual tamping pins. These data were used to determine powder displacement. Powder displacement data were combined with tamping force data to determine work of compaction and perform Heckel analysis. Model formulations, exhibiting classic brittle or plastically deforming type behavior, were evaluated using the instrumented Hofliger Karg GKF 330 by varying overload spring type, pin penetration setting, and number of tamps. Capsule plugs were examined for evidence of particle deformation, plug strength, plug weight, and release of a slightly soluble drug, hydrochlorothiazide. Plugs were evaluated using scanning electron microscopy, BET gas adsorption surface area, and mercury intrusion porosimetry to provide detailed information to the behavior of materials when compacted at low forces. Microcrystalline cellulose based plugs exhibited minimal particle deformation whereas anhydrous lactose based plugs exhibited evidence of fracture. Both formulations exhibited increased plug strength and weight with higher tamping forces which resulted from the use of a larger wire diameter overload spring, increased pin penetration setting, or both. No effect upon the release of hydrochlorothiazide was observed as a result of varying number of tamps or tamping force.