title: Simultaneous quantification of polymeric and surface active stabilizers of nanosuspensions by using near-infrared spectroscopy.
abstract: Nanosuspension technology is an attractive approach for the formulation and solubility enhancement of poorly water-soluble drug compounds. The technology requires adequate excipients for stabilizing the suspensions during nanogrinding and storage. This study aimed at establishing a near-infrared (NIR) method for assaying simultaneously the two nanoparticle stabilizers, sodium dodecyl sulphate (SDS) and hydroxypropylcellulose (HPC), in miconazole nanosuspensions. Second derivative of NIR signals was used to establish calibration curves in concentration ranges of interest of SDS (0.03-0.3%) and HPC (0.75-7.5%). The suitability and applicability of the NIR method was verified by evaluating the linearity, accuracy, precision, and specificity of the obtained data. The method was then used to quantify indirectly the amount of SDS and HPC adsorbed onto miconazole nanoparticles. Within the concentration range of interest, SDS adsorption increased up to 122 µg/m(2) (4.2 × 10(-7) mol/m(2)) with increasing SDS concentration, and HPC adsorption was in the range of 800-1000 µg/m(2) (21-27 × 10(-7) mol/m(2)) for nanosuspensions containing nominally 5% HPC and 12.5% or 20% miconazole. Interestingly, some of the adsorbed HPC was displaced upon increase of SDS concentration and adsorption. The data were also confirmed by surface tension measurements of aqueous solutions of SDS and HPC and nanosuspension supernatants. The availability of a fast and nondestructive method for quantifying simultaneously the adsorption of two stabilizers onto nanoground particles may not only speed up nanosuspension development, but also provide insight into the mechanisms of nanoparticle stabilization regarding competitive adsorption and electrostatic versus steric stabilization.
authors.affiliation: Cilag AG, Schaffhausen, Switzerland.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Cerdeira
authors.forename: Irmgard A
authors.initials: IA
authors.lastname: Werner
authors.forename: Marco
authors.initials: M
authors.lastname: Mazzotti
authors.forename: Bruno
authors.initials: B
authors.lastname: Gander
mesh_terms: D000935:Antifungal Agents / Q000737:chemistry*; D002482:Cellulose / Q000031:analogs & derivatives* / Q000032:analysis; D004355:Drug Stability; D004356:Drug Storage; D005079:Excipients / Q000032:analysis*; D008825:Miconazole / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*; D036103:Nanotechnology; D010316:Particle Size; D012967:Sodium Dodecyl Sulfate / Q000032:analysis*; D012995:Solubility; D019265:Spectroscopy, Near-Infrared; D013499:Surface Properties; D013501:Surface-Active Agents / Q000032:analysis*; D013678:Technology, Pharmaceutical
chemical_list: D000935:Antifungal Agents; D005079:Excipients; D013501:Surface-Active Agents; D012967:Sodium Dodecyl Sulfate; D008825:Miconazole; D002482:Cellulose; C008079:hydroxypropylcellulose