Crystal habit modifications of ibuprofen and their physicomechanical characteristics.

Ibuprofen was crystallized from methanol, ethanol, isopropanol, and hexane at similar conditions. Marked differences in crystal habit of the samples obtained from these solvents were observed. The samples crystallized from methanol and ethanol had a polyhedral crystal habit, while those from hexane were needlelike. Those from isopropanol were elongated crystals. X-ray powder diffraction (XPD) and diferential scanning calorimetry (DSC) studies confirmed that these samples were structurally similar, therefore, polymorphic modifications were ruled out. The results showed that crystal habit modification had a great influence on the mechanical properties (compressibility, flow rate, and bulk density) of ibuprofen crystals. Samples obtained from methanol and ethanol exhibited the highest bulk density and the best flow rate, while those from hexane showed the lowest bulk density and the worst flow rate. The samples obtained from ethanol exhibited the best compression force/hardness profiles, and those obtained from hexane produced the softest tablets.

Effect of compression force, compression speed, and particle size on the compression properties of paracetamol.

The compression characteristics of two particle size fractions (< 90 microm, 105-210 microm) of paracetamol were examined. Each fraction produced extremely weak tablets and displayed a high tendency to cap. Low correlation coefficients of the initial parts of the Heckel plots, a low strain rate sensitivity, and an increase in mean yield pressure (from 34.2 to 45.5 MPa) with decrease in particle size all confirmed that the main mechanism during the compaction of paracetamol was fragmentation. The 105-210-microm particles underwent more fragmentation than the less than 90-microm powder. Heckel analysis confirmed that the larger size fraction of paracetamol produced denser compacts than the smaller fraction. The 105-210-microm fraction resulted in tablets with lower elastic recoveries and elastic energies. The elastic, plastic energy ratios indicated that the majority of energy involved during the compaction of paracetamol was utilized as elastic energy, indicative of massive elastic deformation of paracetamol particles under pressure.

Highly compressible paracetamol: I: crystallization and characterization.

It was found that polyvinylpyrrolidone (PVP) is an effective additive during crystallization of paracetamol and significantly influenced the crystallization and crystal habit of paracetamol. These effects were attributed to adsorption of PVP onto the surfaces of growing crystals. It was found that the higher molecular weights of PVP (PVP 10000 and PVP 50000) were more effective additives than lower molecular weight PVP (PVP 2000). Paracetamol particles obtained in the presence of 0.5% w/v of PVP 10000 or PVP 50000 had near spherical structure and consisted of numerous rod-shaped microcrystals which had agglomerated together. Particles obtained in the presence of PVP 2000 consisted of fewer microcrystals. Differential scanning calorimetry (DSC) and X-ray powder diffraction (XPD) experiments showed that paracetamol particles, crystallized in the presence of PVP, did not undergo structural modifications. By increasing the molecular weight and/or the concentration of PVP in the crystallization medium the amount of PVP incorporated into the paracetamol particles increased. The maximum amount of PVP in the particles was 4.32% w/w.

Highly compressible paracetamol - II. Compression properties.

Paracetamol particles crystallized in the presence of polyvinylpyrrolidone (PVP) exhibited an obvious improvement in their compression properties compared to untreated paracetamol. Paracetamol particles crystallized in the presence of 0.5% w/v PVP 10000 or PVP 50000 produced tablets with improved crushing strength with no tendency to cap even at high compression speeds. The very low values of strain rate sensitivity (SRS) and the lack of reduction in crushing strength with increasing compression speed for these particles, were indicative of a high degree of fragmentation during compression. The results of elastic recoveries and elastic energies of tablets were indicative of much less elastic behaviour of these particles than untreated paracetamol. The low elastic energy/plastic energy (EE/PE) ratio for paracetamol crystallized in the presence of PVP indicated that, contrary to untreated paracetamol, a minor portion of compression energy was utilized as elastic energy.

Formation and compression characteristics of prismatic polyhedral and thin plate-like crystals of paracetamol.

Prismatic polyhedral crystals of paracetamol were prepared by cooling an aqueous saturated solution of paracetamol from 65 to 25 degrees C. Thin plate-like crystals were prepared by adding a concentrated solution of paracetamol in hot ethanol to water at 3 degrees C. Infrared (IR), X-ray powder diffraction (XPD) and differential scanning calorimetry (DSC) studies confirmed that these two forms of crystals were structurally similar, therefore polymorphic modifications were ruled out. The crystal habit influenced the compression properties during axial compression of paracetamol at different constant rates in a compaction simulator, the Heckel plots and their associated constants being dependent on the habits. The correlation coefficient of the initial part of the Heckel plots, and also the values of strain rate sensitivity (SRS), were lower for thin plate-like crystals, indicative of greater fragmentation for the thin plate-like as compared to polyhedral crystals. Compacts made from thin plate-like crystals exhibited higher elastic recoveries and elastic energies indicating that these crystals underwent less plastic deformation during compression than the polyhedral crystals.