title: Hunter screening design to understand the product variability of solid dispersion formulation of a peptide antibiotic.
abstract: The focus of present research was to understand and control the variability of solid dispersion (SD) formulation of non-ribosomal peptide antibiotic, vancomycin (VCM). Hunter screening design was constructed using seven independent variables namely melting temperature (X1), congealing temperature (X2), mixing time (X3), type of capsule shell (X4), filling method (X5), molecular weight of polyethylene glycol (PEG, X6) and surfactant type (X7), and responses measured were cumulative percentage of VCM released in 45 min (Y1) and potency (Y2). The SD formulations were prepared by melt-fusion method, and tested for dissolution, potency, and characterized by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and near infrared chemical imaging (NIR-CI). Statistically significant (p<0.05) effect of congealing temperature (X2), type of capsule shell (X4), filling method (X5), molecular weight of PEG (X6) was revealed on Y1, and R(2) of 0.992 was obtained between experimental and predicted value. None of the factors have statistically significant (p>0.05) influence on Y2. SEM, DSC and PXRD indicated crystalline nature of SD formulations. Homogeneity of SD formulations was shown by NIR-CI images. In summary, the quality of VCM SD formulations could be assured by controlling the critical factors during manufacturing.
authors.affiliation: Division of Product Quality and Research, Center for Drug Evaluation and Research, Food and Drug Administration, MD, USA.
authors.forename: Ziyaur
authors.initials: Z
authors.lastname: Rahman
authors.forename: Mansoor A
authors.initials: MA
authors.lastname: Khan
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000592:standards*; D002626:Chemistry, Pharmaceutical; D004353:Drug Evaluation, Preclinical / Q000379:methods; D010446:Peptide Fragments / Q000737:chemistry / Q000592:standards; D014640:Vancomycin / Q000737:chemistry* / Q000592:standards*; D014961:X-Ray Diffraction / Q000379:methods
chemical_list: D000900:Anti-Bacterial Agents; D010446:Peptide Fragments; D014640:Vancomycin
keywords: Design of experiment; Dissolution; Polyethylene glycol; Potency; Vancomycin