title: Influence of spray drying and dispersing agent on surface and dissolution properties of griseofulvin micro and nanocrystals.
abstract: The purpose for the current research is to compare and evaluate physiochemical properties of spray-dried (SD) microcrystals (MCs), nanocrystals (NCs), and nanocrystals with a dispersion agent (NCm) from a poorly soluble compound. The characterization was carried out by performing size and surface analysis, interfacial tension (at particle moisture interface), and in-vitro drug dissolution rate experiments. Nanosuspensions were prepared by media milling and were spray-dried. The SD powders that were obtained were characterized morphologically using scanning electron microscopy (SEM), polarized light microscopy (PLM), and Flowchem. Solid-state characterization was performed using X-ray powder diffraction (XRPD), Fourier transfer infrared spectroscopy (FT-IR), and differential scanning calorimetry (DSC) for the identification of the crystalline nature of all the SD powders. The powders were characterized for their redispersion tendency in the water and in pH 1.2. Significant differences in redispersion were noted for both the NCs in both dissolution media. The interfacial tension for particle moisture interface was determined by applying the BET (Braunauer-Emmett-Teller) equation to the vapor sorption data. No significant reduction in the interfacial tension was observed between MCs and NCs; however, a significant reduction in the interfacial tension was observed for NCm at both 25 °C and 35 °C temperatures. The difference in interfacial tension and redispersion behavior can be attributed to a difference in the wetting tendency for all the SD powders. The dissolution studies were carried out under sink and under non-sink conditions. The non-sink dissolution approach was found suitable for quantification of the dissolution rate enhancement, and also for providing the rank order to the SD formulations.
authors.affiliation: a Arnold & Marie Schwartz College of Pharmacy and Health Sciences, Long Island University , Brooklyn , NY , USA ;
authors.forename: Dhaval A
authors.initials: DA
authors.lastname: Shah
authors.affiliation: a Arnold & Marie Schwartz College of Pharmacy and Health Sciences, Long Island University , Brooklyn , NY , USA ;
authors.forename: Manan
authors.initials: M
authors.lastname: Patel
authors.affiliation: b Drug Product Design , Pfizer Worldwide R&D , Groton , CT , USA.
authors.forename: Sharad B
authors.initials: SB
authors.lastname: Murdande
authors.affiliation: a Arnold & Marie Schwartz College of Pharmacy and Health Sciences, Long Island University , Brooklyn , NY , USA ;
authors.forename: Rutesh H
authors.initials: RH
authors.lastname: Dave
mesh_terms: D018360:Crystallography, X-Ray; D003890:Desiccation; D005079:Excipients / Q000737:chemistry*; D006118:Griseofulvin / Q000008:administration & dosage*; D008855:Microscopy, Electron, Scanning / Q000379:methods*; D011208:Powders / Q000737:chemistry*; D012995:Solubility; D013499:Surface Properties; D014867:Water / Q000737:chemistry*; D017155:Wettability
chemical_list: D005079:Excipients; D011208:Powders; D014867:Water; D006118:Griseofulvin
keywords: Griseofulvin; interfacial tension; nanocrystals; non-sink dissolution; redispersion; spray dryer