title: Characterization of a nonribosomal peptide antibiotic solid dispersion formulation by process analytical technologies sensors.
abstract: The focus of present investigation was to characterize and evaluate the variability of solid dispersion (SD) of amorphous vancomycin (VCM), utilizing crystalline polyethylene glycol (PEG-6000) as a carrier and subsequently, determining their percentage composition by nondestructive method of process analytical technology (PAT) sensors. The SD were prepared by heat fusion method and characterized for physicochemical and spectral properties. Enhanced dissolution was shown by the SD formulations. Decreased crystallinity of PEG-6000 was observed indicating that the drug was present as solution and dispersed form within the polymer. The SD formulations were homogenous as shown by near infrared (NIR) chemical imaging data. Principal component analysis (PCA) and partial least square (PLS) method were applied to NIR and PXRD (powder X-ray diffraction) data to develop model for quantification of drug and carrier. PLS of both data showed correlation coefficient >0.9934 with good prediction capability as revealed by smaller value of root mean square and standard error. The model based on NIR and PXRD were two folds more accurate in estimating PEG-6000 than VCM. In conclusion, the drug dissolution from the SD increased by decreasing crystallinity of PEG-6000, and the chemometric models showed usefulness of PAT sensor in estimating percentage of both VCM and PEG-600 simultaneously.
authors.affiliation: Division of Product Quality and Research, Center of Drug Evaluation and Research, Food and Drug Administration, Maryland.
authors.forename: Ziyaur
authors.initials: Z
authors.lastname: Rahman
authors.forename: Akhtar
authors.initials: A
authors.lastname: Siddiqui
authors.forename: Mansoor A
authors.initials: MA
authors.lastname: Khan
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry*; D003460:Crystallization; D005079:Excipients / Q000737:chemistry; D016018:Least-Squares Analysis; D011092:Polyethylene Glycols / Q000737:chemistry; D033362:Powder Diffraction; D025341:Principal Component Analysis; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D014640:Vancomycin / Q000737:chemistry*; D014961:X-Ray Diffraction
chemical_list: D000900:Anti-Bacterial Agents; D005079:Excipients; D011092:Polyethylene Glycols; D014640:Vancomycin
keywords: chemometrics; crystal defects; dissolution; fourier infrared spectroscopy; multivariate analysis; partial least square analysis; powder X-ray diffration; principle component analysis; solid dispersion