Layer bonding of solvent-cast thin films for pharmaceutical solid dosage forms

Abstract

In the pharmaceutical industry, the conventional tablet manufacturing process, a batch-based process based on solid powder handling, presents challenges such as inhomogeneous blending between Active Pharmaceutical Ingredients (APIs) and excipients, low yield, and low production rate. These difficulties can be resolved by the realization of a continuous manufacturing process through co-processing of APIs and excipients in the liquid-phase solution. A solvent-cast thin film, produced from liquid solution, can then be manufactured into tablets by way of a folding process. In order to design detailed compaction processes and machines, required compression pressure for layer bonding and mechanical properties of materials should also be investigated. The bonding strength of solvent-cast thin film layers was quantitatively measured by lap shear test. Based on this measurement, bonding threshold pressure was proposed as an indicator showing degree of bonding. At the same time, the layer bonding mechanism of solvent-cast thin films was interpreted as an interdiffusion of amorphous polymer chain end segments. In this context, relative contact area, polymer mobility, which is measured by glass transition temperature, and dwell time were proposed as critical factors in determining bonding threshold pressure. The relationships between those critical factors and process parameters such as surface roughness, residual water and excipient concentration, and compression rate were investigated. The mechanical and viscoelastic properties of solvent-cast thin films were also characterized. Solvent-cast thin films showed ductile-brittle transition, i.e., change of indentation hardness and strength factors among tensile properties with respect to residual water concentration. Changes of creep modulus and tensile properties at various stress levels and strain rates were also observed.