title: Development of novel microprecipitated bulk powder (MBP) technology for manufacturing stable amorphous formulations of poorly soluble drugs.
abstract: A novel method was developed to manufacture amorphous formulations of poorly soluble compounds that cannot be processed with existing methods such as spray drying and melt extrusion. The manufacturing process and the characterization of the resulting amorphous dispersion are presented via examples of two research compounds. The novel process is utilized N,N-dimethylacetamide (DMA) to dissolve the drug and the selected ionic polymer. This solution is then co-precipitated into aqueous medium. The solvent is extracted out by washing and the co-precipitated material is isolated by filtration followed by drying. The dried material is referred to as microprecipitated bulk powder (MBP). The amorphous form prepared using this method not only provides excellent in vitro and in vivo performance but also showed excellent stability. The stabilization of amorphous dispersion is attributed to the high T(g), ionic nature of the polymer that help to stabilize the amorphous form by possible ionic interactions, and/or due to the insolubility of polymer in water. In addition to being an alternate technology for amorphous formulation of difficult compounds, MBP technology provides advantages with respect to stability, density and downstream processing.
authors.affiliation: Pharmaceutical & Analytical R & D, Hoffmann-La-Roche, Nutley, USA.
authors.forename: Navnit
authors.initials: N
authors.lastname: Shah
authors.forename: Harpreet
authors.initials: H
authors.lastname: Sandhu
authors.forename: Wantanee
authors.initials: W
authors.lastname: Phuapradit
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Pinal
authors.forename: Raman
authors.initials: R
authors.lastname: Iyer
authors.forename: Antonio
authors.initials: A
authors.lastname: Albano
authors.forename: Ashish
authors.initials: A
authors.lastname: Chatterji
authors.forename: Shalini
authors.initials: S
authors.lastname: Anand
authors.forename: Duk Soon
authors.initials: DS
authors.lastname: Choi
authors.forename: Kin
authors.initials: K
authors.lastname: Tang
authors.forename: Hung
authors.initials: H
authors.lastname: Tian
authors.forename: Hitesh
authors.initials: H
authors.lastname: Chokshi
authors.forename: Dharmendra
authors.initials: D
authors.lastname: Singhal
authors.forename: Waseem
authors.initials: W
authors.lastname: Malick
mesh_terms: D000081:Acetamides / Q000737:chemistry; D000818:Animals; D000970:Antineoplastic Agents / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D004285:Dogs; D004339:Drug Compounding / Q000379:methods*; D004364:Pharmaceutical Preparations / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D011208:Powders / Q000737:chemistry* / Q000493:pharmacokinetics; D051381:Rats; D012995:Solubility
chemical_list: D000081:Acetamides; D000970:Antineoplastic Agents; D004364:Pharmaceutical Preparations; D011108:Polymers; D011208:Powders; C013959:dimethylacetamide