Scientific Publications by FDA Staff

Int J Pharm 2013 Nov 18;456(2):572-82

Hunter screening design to understand the product variability of solid dispersion formulation of a peptide antibiotic.

Rahman Z, Khan MA

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 45min (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 R2 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.