Discrete particle modeling and micromechanical characterization of bilayer tablet compaction.

A mechanistic particle scale model is proposed for bilayer tablet compaction. Making bilayer tablets involves the application of first layer compaction pressure on the first layer powder and a second layer compaction pressure on entire powder bed. The bonding formed between the first layer and the second layer particles is crucial for the mechanical strength of the bilayer tablet. The bonding and the contact forces between particles of the first layer and second layer are affected by the deformation and rearrangement of particles due to the compaction pressures. Our model takes into consideration the elastic and plastic deformations of the first layer particles due to the first layer compaction pressure, in addition to the mechanical and physical properties of the particles. Using this model, bilayer tablets with layers of the same material and different materials, which are commonly used pharmaceutical powders, are tested. The simulations show that the strength of the layer interface becomes weaker than the strength of the two layers as the first layer compaction pressure is increased. The reduction of strength at the layer interface is related to reduction of the first layer surface roughness. The reduced roughness decreases the available bonding area and hence reduces the mechanical strength at the interface. In addition, the simulations show that at higher first layer compaction pressure the bonding area is significantly less than the total contact area at the layer interface. At the interface itself, there is a non-monotonic relationship between the bonding area and first layer force. The bonding area at the interface first increases and then decreases as the first layer pressure is increased. These results are in agreement with findings of previous experimental studies.

Evolution of the microstructure during the process of consolidation and bonding in soft granular solids.

The evolution of microstructure during powder compaction process was investigated using a discrete particle modeling, which accounts for particle size distribution and material properties, such as plasticity, elasticity, and inter-particle bonding. The material properties were calibrated based on powder compaction experiments and validated based on tensile strength test experiments for lactose monohydrate and microcrystalline cellulose, which are commonly used excipient in pharmaceutical industry. The probability distribution function and the orientation of contact forces were used to study the evolution of the microstructure during the application of compaction pressure, unloading, and ejection of the compact from the die. The probability distribution function reveals that the compression contact forces increase as the compaction force increases (or the relative density increases), while the maximum value of the tensile contact forces remains the same. During unloading of the compaction pressure, the distribution approaches a normal distribution with a mean value of zero. As the contact forces evolve, the anisotropy of the powder bed also changes. Particularly, during loading, the compression contact forces are aligned along the direction of the compaction pressure, whereas the tensile contact forces are oriented perpendicular to direction of the compaction pressure. After ejection, the contact forces become isotropic.

Release of chlorpheniramine maleate from fatty acid ester matrix disks prepared by melt-extrusion.

Chlorpheniramine maleate was incorporated into disks consisting of glyceryl fatty acid esters, polyethylene glycol fatty acid esters or a combination of the two. A melt-extrusion process was used to prepare the matrix disks containing the drug. The release of the drug into distilled water, pH 1.2 buffer, and pH 7.5 buffer showed the expected square root of time dependence. An increase in the fatty acid ester hydrophilic-lipophilic balance (HLB) from 1 to 14 resulted in a 10-fold increase in the drug release rate from 0.25 +/- 0.01 to 25.84 +/- 1.29 mg cm-2 h-1/2. The maximum release rate was seen from the fatty acid ester with a melting point of 44 degrees C. The pH of the dissolution medium had a small impact on the rate of drug release, but the rate of agitation had no significant influence on the rate of drug release. By blending a fatty acid ester of a high melting point (64 degrees C) and a low HLB value of 2 with esters of lower melting points (33 to 50 degrees C) or higher HLB values (10 to 14), it was possible to modify the release from 10.0 +/- 0.70 to 21.5 +/- 0.57 mg cm-2 h-1/2.

Permeability of cellulose polymers: water vapour transmission rates.

The water vapour transmission rates (WVTR) through solvent cast polymer films prepared from cellulose acetate, cellulose acetate propionate, and cellulose acetate butyrate have been determined. They were influenced by the relative humidity, the substituent type and the extent of substitution. Increasing the relative humidity from 32 to 90% increased the WVTR 3 to 5 times depending on the polymer used. The WVTR increased in the order of butyrate less than propionate less than acetate. An increase in the extent of substitution with acetyl and/or butyryl groups resulted in an exponential decline in the WVTR.