title: Application of spray granulation for conversion of a nanosuspension into a dry powder form.
abstract: The in vivo effect of particle agglomeration after drying of nanoparticles has not been extensively studied till date based on current literature review. The purpose of this research was to evaluate the feasibility of spray granulation as a processing method to convert a nanosuspension of a poorly water soluble drug into a solid dosage form and to evaluate the effect of the transformation into a solid powder on the in vivo exposure in beagle dogs. Formulation variables like the level of stabilizer in the nanosuspension formulation, granulation substrate and drug loading in the granulation were evaluated. The granules were characterized for moisture content, drug content, particle size, crystallinity and in vitro dissolution rate. Granulations with 10% drug loading showed dissolution profiles comparable to the nanosuspension, slightly slower dissolution profiles were observed at 20% drug loading. This can be attributed to an increase in the surface hydrophobicity at a higher drug loading and the formation of agglomerates that were harder to disintegrate, thereby compromising the dissolution rate. An in vivo PK study in beagle dogs showed an 8-fold increase and a 6-fold increase in the AUC(0-48) from the nanosuspension and dried nanosuspension formulations respectively compared to the coarse suspension. Also, the nanosuspension and dried nanosuspension formulations showed a 12-fold and 8-fold increase in the C(max) respectively compared to the coarse suspension. This shows the feasibility of using spray granulation as a processing method to convert a nanosuspension into a solid dosage form with improved in vivo exposure compared to the coarse suspension formulation.
authors.affiliation: Pharmaceutical and Analytical Development, Novartis Pharmaceuticals Corporation, One Health Plaza, East Hanover, NJ 07936, USA. sonali.bose@novartis.com
authors.forename: Sonali
authors.initials: S
authors.lastname: Bose
authors.forename: Daniel
authors.initials: D
authors.lastname: Schenck
authors.forename: Indrajit
authors.initials: I
authors.lastname: Ghosh
authors.forename: Al
authors.initials: A
authors.lastname: Hollywood
authors.forename: Ester
authors.initials: E
authors.lastname: Maulit
authors.forename: Colleen
authors.initials: C
authors.lastname: Ruegger
mesh_terms: D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004285:Dogs; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry*; D010316:Particle Size; D011208:Powders / Q000008:administration & dosage* / Q000737:chemistry*; D012995:Solubility; D013535:Suspensions / Q000008:administration & dosage* / Q000737:chemistry*; D014867:Water / Q000737:chemistry; D014961:X-Ray Diffraction / Q000379:methods
chemical_list: D011208:Powders; D013535:Suspensions; D014867:Water