Powder Compaction: Compression Properties of Cellulose Ethers

Effective development of matrix tablets requires a comprehensive understanding of different raw material attributes and their impact on process parameters. Cellulose ethers (CE) are the most commonly used pharmaceutical excipients in the fabrication of hydrophilic matrices. The innate good compression and binding properties of CE enable matrices to be prepared using economical direct compression (DC) techniques. However, DC is sensitive to raw material attributes, thus, impacting the compaction process. This article critically reviews prior knowledge on the mechanism of powder compaction and the compression properties of cellulose ethers, giving timely insight into new developments in this field

Effects of water vapor absorption on the physical and chemical stability of amorphous sodium indomethacin

This study reports on the effects that water absorbed into amorphous sodium indomethacin (NaIMC) can have on simultaneous tendencies to crystallize to its trihydrate form and to undergo base-catalyzed hydrolysis because of the plasticizing effects of water on molecular mobility. Measurement of water vapor absorption at 30°C and powder x-ray diffraction patterns as a function of relative humidity (RH) reveal that upon exposure to 21% RH, NaIMC does not crystallize over a 2-month period. Measurements of the glass transition temperature as a function of such exposure reveals a change in Tg from 121°C, dry, to 53°C at 21% RH, such that Tg at 21% RH is ≈13°C above the highest storage temperature of 40°C used in the study. At 56% RH and higher, however, crystallization to the trihydrate occurs rapidly; although over the 2-month period, crystallization was never complete. Assessment of chemical degradation by high-performance liquid chromatography analysis revealed significant instability at 21% RH; whereas at higher RH, the extent of chemical degradation was reduced, reflecting the greater crystallization to the more chemically stable crystalline form. It is concluded that when amorphous forms of salts occur in solid dosage forms, the simultaneous effects of enhanced water vapor sorption on crystallization and chemical degradation must be considered, particularly when assessing solid-state chemical degradation at higher temperatures and RH (eg, 40°C 75% RH)

The protective effect of lactose on lyophilization of CNK-20402

The goal of this research was to assess the feasibility of using lyophilization to stabilize an exploratory compound, CNK-20402, with a minimal amount of impurity (CNK-20193) formation. A mixed-level full factorial experimental design was used to screen excipients of glycine, mannitol, lactose monohydrate, and povidone K-12. Cryostage microscopy, powder X-ray diffraction, Karl Fischer titration, HPLC, and water vapor sorption were used to assess the formulations' physicochemical properties and stability. Initial physical characterization from powder X-ray diffraction revealed that the mannitol- and glycine-containing formulations were crystalline with the patterns of the pure excipient, whereas the remaining formulations were amorphous in structure. Chemically, the formulations stored at 50°C for 1 month had 2.36%, 1.05%, 0.81%, 0.79%, and 0.49% CNK-20193 for glycine, mannitol, drug alone, povidone K-12, and lactose formulations, respectively. The formulations containing drug-mannitol, drug alone, and druglactose were selected for accelerated stability study based on statistical analysis. Recovery of CNK-20193 in these formulations was 1.22%, 1.00%, and 0.55%, respectively, when stored at 40°C/75% relative humidity storage conditions for 3 months. Water vapor sorption analysis revealed weight gains of over 7%, 21%, and 24% for the mannitol, lactose, and drug alone formulations, respectively. Testing formulations with different concentrations of lactose by water vapor sorption indicated that CNK-20402 concentrations as low as 10% (wt/wt) could inhibit the recrystallization of lactose. The lactose-containing formulation exhibited the best stability among the formulations tested. The protective mechanism of lactose on the CNK-20402, based on water vapor sorption studies, is believed to be a result of (1) the drug-lactose interaction, and (2) competition between lactose and drug for the residual water in the formulation

γ-irradiation of PEGd,lPLA and PEG-PLGA Multiblock Copolymers: II. Effect of Oxygen and EPR Investigation

The purpose of this research was to evaluate how the presence of oxygen can affect irradiation-induced degradation reactions of PEGd,lPLA and PEG-PLGA multiblock copolymers submitted to gamma irradiation and to investigate the radiolytic behavior of the polymers. PEGd,lPLA, PEG-PLGA, PLA, and PLGA were irradiated by using a 60Co irradiation source in air and under vacuum at 25 kGy total dose. Mw and Mn were evaluated by gel permeation chromatography. The stability study was carried out on three samples sets: (a) polymer samples irradiated and stored in air, (b) polymer samples irradiated and stored under vacuum, and (c) polymer samples irradiated under vacuum and stored in air. The thermal and radiolytic behavior was investigated by differential scanning calorimetry and electron paramagnetic resonance (EPR), respectively. Samples irradiated in air showed remarkable Mw and Mn reduction and Tg value reduction due to radiation-induced chain scission reactions. Higher stability was observed for samples irradiated and stored under vacuum. EPR spectra showed that the presence of PEG units in multiblock copolymer chains leads to: (a) decrease of the radiolytic yield of radicals and (b) decrease of the radical trapping efficiency and faster radical decay rates. It can be concluded that the presence of oxygen during the irradiation process and the storage phase significantly increases the entity of irradiation-induced damage

Nanoscale characterisation and imaging of partially amorphous materials using local thermomechanical analysis and heated tip AFM

The purpose is to investigate the use of thermal nanoprobes in thermomechanical and heated tip pulsed force modes as novel means of discriminating between amorphous and crystalline material on a sub-micron scale. Indometacin powder was compressed and partially converted into amorphous material. Thermal nanoprobes were used to perform localised thermomechanical analysis (L-TMA) and heated tip pulsed force mode imaging as a function of temperature. L-TMA with submicron lateral spatial resolution and sub-100 nm depth penetration was achieved, allowing us to thermomechanically discriminate between amorphous and crystalline material at a nanoscale for the first time. The amorphous and crystalline regions were imaged as a function of temperature using heated tip pulsed force AFM and a resolution of circa 50 nm was achieved. We are also able to observe tip-induced recrystallisation of the amorphous material. The study demonstrates that we are able to discriminate and characterise amorphous and crystalline regions at a submicron scale of scrutiny. We have demonstrated the utility of two methods, L-TMA and heated tip pulsed force mode AFM, that allow us to respectively characterise and image adjacent amorphous and crystalline regions at a nanoscale. The study has demonstrated that thermal nanoprobes represent a novel method of characterising and imaging partially amorphous materials

Effects of physical properties for starch acetate powders on tableting

The aim of the study was to investigate particle and powder properties of various starch acetate powders, to study the effect of these properties on direct compression characteristics, and to evaluate the modification opportunity of physical properties for starch acetate powders by using various drying methods. At the end of the production phase of starch acetate, the slurry of starch acetate was dried using various techniques. Particle, powder, and tableting properties of end products were investigated. Particle size, circularity, surface texture, water content and specific surface area varied according to the particular drying method of choice. However, all powders were freely flowing. Bulk and tapped densities of powders varied in the range of 0.29 to 0.44 g/cm3 and 0.39 to 0.56 g/cm3, respectively. Compaction characteristics revealed that all powders were easily deformed under compression, having yield pressure values of less than 66 MPa according to Heckel analysis. All powders possessed a significant interparticulate bond-forming capacity during compaction. The tensile strength values of tablets varied between 10 and 18 MPa. In conclusion, physical properties of starch acetate could be affected by various drying techniques. A large specific surface area and water content above 4% were favorable properties by direct compression, especially for small, irregular, and rough particles