PURPOSE: This study aimed to investigate the effect of a model protein on the solid state of a commonly used bulk agent in spray-dried formulations. METHODS: A series of lysozyme/mannitol formulations were spray-dried using a lab-scale spray dryer. Further, the surface temperature of drying droplet/particles was monitored using the DRYING KINETICS ANALYZER™ (DKA) with controllable drying conditions mimicking the spray-drying process to estimate the drying kinetics of the lysozyme/mannitol formulations. The mannitol polymorphism and the spatial distribution of lysozyme in the particles were examined using X-ray powder diffractometry (XRPD) and Raman microscopy. Partial Least Squares Discriminant Analysis was used for analyzing the Raman microscopy data. RESULTS: XRPD results indicated that a mixture of β-mannitol and α-mannitol was produced in the spray-drying process which was supported by the Raman analysis, whereas Raman analysis indicated that a mixture of α-mannitol and δ-mannitol was detected in the single particles from DKA. In addition Raman mapping indicated that the presence of lysozyme seemed to favor the appearance of α-mannitol in the particles from DKA evidenced by close proximity of lysozyme and mannitol in the particles. CONCLUSIONS: It suggested that the presence of lysozyme tend to induce metastable solid state forms upon the drying process.
PURPOSE: This study aimed to investigate the effect of a model protein on the solid state of a commonly used bulk agent in spray-dried formulations. METHODS: A series of lysozyme/mannitol formulations were spray-dried using a lab-scale spray dryer. Further, the surface temperature of drying droplet/particles was monitored using the DRYING KINETICS ANALYZER™ (DKA) with controllable drying conditions mimicking the spray-drying process to estimate the drying kinetics of the lysozyme/mannitol formulations. The mannitol polymorphism and the spatial distribution of lysozyme in the particles were examined using X-ray powder diffractometry (XRPD) and Raman microscopy. Partial Least Squares Discriminant Analysis was used for analyzing the Raman microscopy data. RESULTS: XRPD results indicated that a mixture of β-mannitol and α-mannitol was produced in the spray-drying process which was supported by the Raman analysis, whereas Raman analysis indicated that a mixture of α-mannitol and δ-mannitol was detected in the single particles from DKA. In addition Raman mapping indicated that the presence of lysozyme seemed to favor the appearance of α-mannitol in the particles from DKA evidenced by close proximity of lysozyme and mannitol in the particles. CONCLUSIONS: It suggested that the presence of lysozyme tend to induce metastable solid state forms upon the drying process.
Authors: Denise M Croker; Michelle C Hennigan; Anthony Maher; Yun Hu; Alan G Ryder; Benjamin K Hodnett Journal: J Pharm Biomed Anal Date: 2012-01-18 Impact factor: 3.935
Authors: F Tian; F Zhang; N Sandler; K C Gordon; C M McGoverin; C J Strachan; D J Saville; T Rades Journal: Eur J Pharm Biopharm Date: 2006-12-13 Impact factor: 5.571
Authors: H R Costantino; J D Andya; P A Nguyen; N Dasovich; T D Sweeney; S J Shire; C C Hsu; Y F Maa Journal: J Pharm Sci Date: 1998-11 Impact factor: 3.534