1.
Heidarian, Mina, et al.
(författare)
Influence of water-cellulose binding energy on stability of acetylsalicylic acid
2006
Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 323:1-2, s. 139-145
Tidskriftsartikel (refereegranskat) abstract
The aim of the present study was to investigate how the energies of water binding in cellulose tabletting excipients influence the availability of moisture to induce hydrolysis of acetylsalisylic acid (ASA). Cellulose powders of varying degree of order, denoted as low-crystallinity cellulose (LCC) and high-crystallinity cellulose (HCC), were produced by treating ordinary microcrystalline cellulose (MCC) in ZnCl2 solutions of varying concentrations. Microcrystalline cellulose (MCC) and lactose monohydrate were used as reference excipients. The samples were then studied by X-ray diffraction, scanning electron microscopy, and differential scanning calorimetry (DSC). Different ratios of each excipient mixed with ASA were stored at 40% RH and 50 degrees C for 35 days to investigate the hydrolytic stability of the mixtures. Stability studies indicated that as concentration of HCC and MCC in binary mixtures with ASA was raised from 1 to 50% (w/w), ASA became increasingly unstable with respect to hydrolysis. Although LCC contained more moisture than the other celluloses, no such trend was observed in the LCC and lactose samples. DSC analysis revealed that each water molecule on the average was bound by more than three hydrogen bonds in the LCC and lactose structures and therefore remained predominantly unavailable to induce hydrolysis. The current study elucidates the necessity of evaluating the energy of water bindings in a pharmaceutical excipient when predicting the excipient's performance in mixtures comprising moisture-sensitive drugs.
2.
Nilsson, Martin, et al.
(författare)
Mesopore structure of microcrystalline cellulose tablets characterized by nitrogen adsorption and SEM : The influence on water-induced ionic conduction
2006
Ingår i: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 110:32, s. 15776-15781
Tidskriftsartikel (refereegranskat) abstract
Tablets of microcrystalline cellulose were formed at different compaction pressures and physical properties, such as pore size distribution, surface area, and pore surface fractality, were extracted from N-2 adsorption isotherms. These properties were compared to previously published data on the water-induced ionic conductivity of the tablets. The conduction process was shown to follow a percolation model with a percolation exponent of 2 and a porosity percolation threshold of similar to 0.1. The critical pore diameter for facilitated charge transport was shown to be in the 5-20 nm range. When the network of pores with a diameter in this interval is reduced to the point where it no longer forms a continuous passageway throughout the compact, the conduction process is dominated by charge transport on the surfaces of individual microfibrils mainly situated in the bulk of fibril aggregates. A fractal analysis of nitrogen adsorption isotherms showed that the dominant interface forces during adsorption is attributed to surface tensions between the gas and the adsorbed liquid phase. The extracted fractal dimension of the analyzed pore surfaces remained unaffected by the densification process at low compaction pressures (< similar to 200 MPa). At increased densification, however, pore-surface structures smaller than similar to 100 nm become smoother as the fractal dimension decreases from similar to 2.5 at high porosities to similar to 2.3 for the densest tablets under study.
