Browsing by Subject "capsule"

In early clinical trials of drug development capsule is preferable compared with other solid dosage forms, including tablets, because of its simplicity and blinding capabilities. However a simple capsule formulation is not viable in large-scale production. Usually it's either switched to an economical tablet formulation or to another capsule formulation that can be manufactured on large-scale equipment. Tablets are nearly always formulated for commercialization if they're not technologically impossible to manufacture for a reason which could be bad compression or solubility of a drug. Tablet-pressing process sets more-demanding requirements for pharmaceutical powder properties than encapsulation process, because tablet-press uses larger compression forces and it measures the dose in a different way. The most common problems faced when switching from a capsule dosage form to tablet-pressing process are poor powder flow properties and weak mechanical strength, capping and lamination of tablets. The purpose of this work was to investigate the critical pharmaceutical and technical properties to succeed in switching from a capsule dosage form to a tablet dosage form and tablet-pressing process. The starting point of this work was a simple capsule formulation consisting of carbidopa, directcompressible mannitol and pregelatinized maize starch. The simple formulation was used to build up two mixture designs consisting of very different powder properties to study the critical powder properties and process variables involved in the switch. The capsules were filled on a dosating nozzle capsule-filling machine and the tablets were pressed on a pneumohydraulic tablet press. Weight variability, disintegration time, encapsulation and tabletability were used as the responses of the dosage forms. As a result of the study the automatic capsule-filling machine filled many different types of powders in capsules with low fill-weight variability. The most critical powder properties affecting the capsulefilling process were the particle size, bulk and tapped densities and cohesion of powder. Avicel PH200 improved the tabletability and flowability of the powders, but it also increased the fill-weight variability of the capsules. In this work single powder flow properties described only the flowability of a powder, but they did not determine the performance of a powder in the processes. Therefore, measuring various powder flow properties and correlating them to a manufacturing system is necessary to understand the process. Avicel PH102 was proved to work as an ideal reference material for evaluating the sufficiency of the flow properties of a powder in the tablet-pressing process.