title: Formulation and evaluation of a protein-loaded solid dispersions by non-destructive methods.
abstract: The purpose of this investigation was to develop solid dispersion (SD) formulation of cyclosporine (CyA) using polyethylene glycol (PEG-6000) to enhance its dissolution rate followed by nondestructive method for the prediction of both drug and carrier. SD formulations were prepared by varying the ratio of CyA and PEG-6000 by solvent evaporation technique and characterized by dissolution, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), Fourier transform infrared (FTIR), powder X-ray diffraction (PXRD), near infrared (NIR) and near infrared chemical imaging (NIR-CI). Dissolution data revealed enhanced dissolution of CyA when compared with pure CyA. DSC results showed that the crystallinity of PEG-6000 has decreased as indicated by decrease in the enthalpy of fusion and melting peak in the formulations. FTIR data demonstrated no chemical interaction between drug and carrier. The surface morphology of SD formulations was similar to PEG-6000 particle. NIR-CI disclosed homogeneity of SD matrix as indicated by symmetrical histograms with smaller values of skewness. Similar to NIR, a multivariate peak evaluation with principal component analysis and partial least square (PLS) were carried out with PXRD spectral data. PLS models with both techniques showed good correlation coefficient and smaller value of root mean square of errors. The accuracy of model for predicting CyA and PEG-6000 in NIR and PXRD data were 5.22%, 5.35%, 5.27%, and 2.10%, respectively. In summary, chemometric applications of non-destructive method sensors provided a valuable means of characterization and estimation of drug and carrier in the novel formulations.
authors.affiliation: Division of Product Quality and Research, Center of Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA.
authors.forename: Ziyaur
authors.initials: Z
authors.lastname: Rahman
authors.forename: Ahmed S
authors.initials: AS
authors.lastname: Zidan
authors.forename: Mansoor A
authors.initials: MA
authors.lastname: Khan
mesh_terms: D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D016572:Cyclosporine / Q000008:administration & dosage / Q000737:chemistry; D004337:Drug Carriers; D005079:Excipients; D007700:Kinetics; D008855:Microscopy, Electron, Scanning; D011092:Polyethylene Glycols; D011506:Proteins / Q000008:administration & dosage / Q000737:chemistry*; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D019265:Spectroscopy, Near-Infrared; D014961:X-Ray Diffraction
chemical_list: D004337:Drug Carriers; D005079:Excipients; D011506:Proteins; D011092:Polyethylene Glycols; D016572:Cyclosporine