Curcuma longa L. is a traditional medicinal and spice plant containing a variety of lipophilic active substances with promising therapeutic properties. In this work, the solvent properties of supercritical carbon dioxide in a pressure and temperature range of 75–425 bar and 35–75 °C were investigated when Curcuma longa rhizomes were extracted. The three main curcuminoids, namely curcumin, demethoxycurcumin, and bisdemethoxycurcumin, together with the three main constituents of the essential oil, i.e., ar-turmerone, α-turmerone, and β-turmerone, were analyzed in the resulting extracts. For statistical evaluation, experiments were performed employing a full factorial design, in which flow rate, extraction time, and drug load were kept constant. Within the given conditions, the experimental design revealed an optimum yield of all aforementioned substances, when supercritical carbon dioxide extraction was performed at 425 bar and 75 °C. For comparison, solvent extracts using methanol and n-hexane were prepared and their main components were characterized using LC-MS. The stability of the extracts was monitored upon storage for 6 months at 22 and 40 °C under protection from light. The decomposition of individual compounds was mainly observed in the presence of residual water in the extracts.
Hydrate formation is a phase transition which can occur during manufacturing processes involving water. This work considers the prevention of hydration of anhydrous olanzapine and hydrate conversions in the presence of water and polymers (polyethyleneglycol; hydroxypropylcellulose; polyvinylpyrrolidone) in forming pellets by wet extrusion and spheronisation. Anhydrous olanzapine was added to water with or without those polymers prior to extrusion with microcrystalline cellulose. Assessment of olanzapine conversion was made by XRP-Diffraction; FTIR spectroscopy; calorimetry (DSC) and microscopy (SEM for crystal size and shape). The addition of water converted the anhydrous form into dihydrate B and higher hydrate; whereas polyethyleneglycol promoted a selective hydrate conversion into the higher hydrate olanzapine form. Both polyvinylpyrrolidone and hydroxypropylcellulose prevented the hydrate transformations of the anhydrous drug; the latter even in the presence of hydrate seeds. This may be explained by the higher H-bond ability; higher network association and higher hydrophobicity of hydroxypropylcellulose by comparison with polyethyleneglycol and polyvinylpyrrolidone; which could contribute to its higher affinity to the crystal surfaces of the hydrate nuclei/initial crystals and promoting steric hindrance to the incorporation of other drug molecules into the crystal lattice; thus, preventing the crystal growth. The addition of microcrystalline cellulose needed for the pellets production (final product) did not eliminate the protector effect of both hydroxypropylcellulose and polyvinylpyrrolidone during pellets’ processing and dissolution evaluation.
1 October 2008 in Journal of Pharmaceutical Sciences