Surface energy of microcrystalline cellulose determined by capillary intrusion and inverse gas chromatography.

Surface energy data for samples of microcrystalline cellulose have been obtained using two techniques: capillary intrusion and inverse gas chromatography. Ten microcrystalline cellulose materials, studied using capillary intrusion, showed significant differences in the measured surface energetics (in terms of total surface energy and the acid-base characteristics of the cellulose surface), with variations noted between the seven different manufacturers who produced the microcrystalline cellulose samples. The surface energy data from capillary intrusion was similar to data obtained using inverse gas chromatography with the column maintained at 44% relative humidity for the three samples of microcrystalline cellulose studied. This suggests that capillary intrusion may be a suitable method to study the surface energy of pharmaceutical samples.

Interaction of moisture with sodium starch glycolate.

The relationship between the apparent moisture content and moisture sorption of modified starches was investigated. Samples of sodium starch glycolate (SSG), pregelatinized starch (PGS) and potato starch (PS) were stored for various times at 44% or 75% relative humidity (RH) to produce samples with moisture contents of up to 14%, as determined by loss on drying (LOD). Evaluation of LOD and mass gain data suggested that measured mass gain equated to predicted LOD values for PGS and PS. However, in SSG there was a nonstoichiometric relationship between mass gain and predicted LOD. In addition, samples of SSG displayed hysteresis during dynamic vapor sorption (DVS) cycling in that an apparent mass loss of about 2-3% was observed for two of the SSGs, with PS and PGS exhibiting reversibility. In some cases, SSG exhibited an apparent mass loss during the DVS cycle at with 50% RH. These observations suggest that one or more of the components of SSG "interact" with moisture. Because X-ray diffraction suggested there was no dramatic change in the crystallinity of SSG, an exchange of residual SSG solvent, alcohol, with moisture may, in part, explain the moisture sorption behavior of SSG.

Effect of moisture on the compressibility and compactibility of sodium starch glycolate.

The relationship between the apparent moisture content and compactibility of sodium starch glycolate was compared to similarly obtained data for pregelatinized starch. Samples of sodium starch glycolate (SSG) and pregelatinised starch (PGS) were stored at 44% or 75% relative humidity (RH), producing samples exhibiting moisture contents of up to 14% w/w, as determined by loss on drying (LOD). Increasing the moisture content of SSG and PGS resulted in an increase in compressibility and compactibility for both materials. However, the effect was more dramatic for SSG with unlubricated compactibilities of 2.0 MPa and 0.9 MPa at approximately 11.5% LOD for SSG and PGS, respectively, which was further exemplified in the compactibility of lubricated materials and in blends with microcrystalline cellulose. These results suggested that moisture content had a greater effect on the compactibility of SSG compared with PGS and that the interactions of water with the components of the SSG starch granules may be different from those within the PGS starch granules at comparable LOD values.

Dynamic vapor sorption properties of sodium starch glycolate disintegrants.

Dynamic vapor sorption (DVS) was used to determine the moisture sorption properties of sodium starch glycolates. The results were compared to similarly obtained data for potato starch, pregelatinized starch, microcrystalline cellulose (MCC), and crystalline lactose. As expected, sodium starch glycolates exhibit a large mass gain at 90% relative humidity (RH), compared to the other anhydroglucose-based excipients. However, the sorption capacities of potato starch and the modified starches between 10%-70% RH were similar. Analysis of the DVS data using the Brunauer-Emmett-Teller (BET) and Guggenheim, Anderson, and deBoer (GAB) theories to obtain the so-called monolayer (Xm), as expected, showed that there was an increasing Xm with apparent mass gain that is probably related to crystallinity, purity, and surface area and represents the number and accessibility of amorphous anhydroglucose units present. The value of x(m) was related to the degree of crystallinity or order as determined by X-ray diffraction, suggesting that x(m) can be used to further describe the amorphous nature of semi-crystalline polymers containing anhydroglucose units, in particular the chemically modified sodium starch glycolate. Additionally, it appears that the sorption capacity between 10%-70% RH is not dramatically affected by the presence or type of cross-linking and sodium carboxymethylation (in sodium starch glycolates) and gelatinization (in pregelatinized starch) and that the superdisintegrant properties of the sodium starch glycolates are a consequence of some water-structure interaction that is well beyond the available number of hydration sites, as represented by x(m). Further evaluation of the structure and sorption properties of excipients may aid the development of disintegrants for solid dosage forms.

Physicochemical and mechanical evaluation of a novel high density grade of silicified microcrystalline cellulose.

High density microcrystalline cellulose (MCC) is a relatively free flowing grade of MCC that finds use in direct compression tableting and hard gelatin capsule filling applications. Silicified high density microcrystalline cellulose has recently been introduced. This material has been compared to other grades of MCC and previously silicified microcrystalline cellulose (SMCC). The results suggest that, as observed for other grades of SMCC, the material exhibits no detectable chemical or polymorphic differences to standard material, some improvement in flow characteristics, but shows considerably enhanced mechanical properties.

The potential use of Raman mapping to investigate in vitro deposition of combination pressurized metered-dose inhalers.

Scanning near-infrared Raman microscopy has been used to map aerosol particulate deposits produced from pressurized metered-dose inhalers (pMDI). A commercially available combination asthma therapy pMDI (Ventide, Allen and Hanbury, UK), containing salbutamol and beclometasone dipropionate, was analyzed by conventional in vitro quantitative analysis and scanning Raman microscopy. Raman maps, taken from Andersen cascade impactor plate stages 3 and 5 (over 100 x 100 microm areas) suggested good correlation with chemical analysis of the respective stages. Scanning Raman microscopy allows visual differentiation between formulation components (not possible using conventional imaging techniques), while potentially allowing chemical quantification.

Adsorption of an amine drug onto microcrystalline cellulose and silicified microcrystalline cellulose samples.

The adsorption of a model amine drug (tacrine hydrochloride) from aqueous solution onto 21 microcrystalline cellulose (MCC) based samples has been investigated. The MCC source (manufacturer) affected adsorption. The adsorption appeared to be fully reversible. Adsorption was reduced by the use of high-density grade MCC, high-energy milling, and silicification. Adsorption of the model drug was not affected by the particle size of the MCC. Significant variations of the adsorption characteristics between batches of certain MCC products were found. The primary mode of adsorption was by ion exchange.