sodium-acetate--anhydrous and Breast-Neoplasms

It is hypothesized that a novel crystalline solid dispersion (CSD) of docetaxel (C-DXT) can be engineered by dispersing native docetaxel (DXT, a BCS class II drug) in sodium acetate crystal (SA). DXT is dissolved in glacial acetic/SA solution and freeze-dried. The resulting C-DXT is characterized by differential scanning calorimetry (DSC), powder X-ray analysis (PXRD), LC-MS/MS, scanning electron microscopy (SEM), transmission electron microscopy (TEM), Quartz crystal microbalance with dissipation monitoring (QCM-D) and dynamic light scattering (DLS). Its cytotoxicity on model cancerous (MCF-7, MDA-MB-468) and normal breast cells (MCF-10A) is assessed by MTS assay. SEM/TEM data and the absence of the characteristics peaks of DXT on the DSC curve (at 193.4 °C) and the XRD scan (at 2θ = 15.31 °C and 23.04 °C) confirm the presence of C-DXT in SA. The LC-MS/MS data indicates the chemical stability of DXT. The yield and C-DXT loading are 95.2% and 6.52% w/w, respectively. The C-DXT rapidly forms an aqueous non-rigid nanosuspension with a faster drug dissolution rate compared to native DXT. Unlike, control Tween 80/ethanol, SA is noncytotoxic to normal cells. However, C-DXT's cytotoxicity is time and dose dependent for all diseased cells. This unique CSD process might be applicable to other hydrophobic bioactive agents to enhance their safety and efficacy.

Topics: Antineoplastic Agents; Breast Neoplasms; Calorimetry, Differential Scanning; Cell Survival; Chromatography, Liquid; Crystallization; Crystallography, X-Ray; Docetaxel; Dose-Response Relationship, Drug; Drug Compounding; Dynamic Light Scattering; Female; Humans; Hydrophobic and Hydrophilic Interactions; Kinetics; MCF-7 Cells; Microscopy, Electron, Scanning; Microscopy, Electron, Transmission; Particle Size; Powder Diffraction; Sodium Acetate; Solubility; Tandem Mass Spectrometry; Taxoids; Technology, Pharmaceutical; Water