title: Development of a fast, lean and agile direct pelletization process using experimental design techniques.
abstract: A novel hot melt direct pelletization method was developed, characterized and optimized, using statistical thinking and experimental design tools. Mixtures of carnauba wax (CW) and HPMC K100M were spheronized using melted gelucire 50-13 as a binding material (BM). Experimentation was performed sequentially; a fractional factorial design was set up initially to screen the factors affecting the process, namely spray rate, quantity of BM, rotor speed, type of rotor disk, lubricant-glidant presence, additional spheronization time, powder feeding rate and quantity. From the eight factors assessed, three were further studied during process optimization (spray rate, quantity of BM and powder feeding rate), at different ratios of the solid mixture of CW and HPMC K100M. The study demonstrated that the novel hot melt process is fast, efficient, reproducible and predictable. Therefore, it can be adopted in a lean and agile manufacturing setting for the production of flexible pellet dosage forms with various release rates easily customized between immediate and modified delivery.
authors.affiliation: a Department of Pharmacy, National and Kapodistrian University of Athens , Panepistimiopolis Zografou , Athens , Greece.
authors.forename: Stavros N
authors.initials: SN
authors.lastname: Politis
authors.affiliation: a Department of Pharmacy, National and Kapodistrian University of Athens , Panepistimiopolis Zografou , Athens , Greece.
authors.forename: Dimitrios M
authors.initials: DM
authors.lastname: Rekkas
mesh_terms: D004343:Drug Implants / Q000737:chemistry*; D005079:Excipients / Q000737:chemistry; D005223:Fats / Q000737:chemistry; D065347:Hypromellose Derivatives / Q000737:chemistry; D009821:Oils / Q000737:chemistry; D011109:Polymethacrylic Acids / Q000737:chemistry; D011208:Powders / Q000737:chemistry; D012107:Research Design; D013678:Technology, Pharmaceutical / Q000379:methods*; D014885:Waxes / Q000737:chemistry
chemical_list: D004343:Drug Implants; D005079:Excipients; D005223:Fats; D009821:Oils; D011109:Polymethacrylic Acids; D011208:Powders; D014885:Waxes; C071184:Gelucire 50-13; D065347:Hypromellose Derivatives; C012553:spherons; C026344:carnauba wax
keywords: Direct pelletization; agile; customized drug release; experimental design; hot melt, modified release; lean; process knowledge