title: Application of a hot-melt granulation process to enhance fenofibrate solid dose manufacturing.
abstract: Evaluation of hot-melt granulation of fenofibrate and croscarmellose sodium and its cooling time for the molten mass in a ratio of 55:45 was conducted to assess the manufacturing process capability to produce an acceptable granulation which flows well on Korsch PH300 tablet compression machine. The formation of the drug-polymer eutectic mixture was investigated by differential scanning calorimetry, scanning electron microscopy and X-ray powder diffraction. The physical properties of the hot-melt was determined by examining the milled blocks after solidification and milling after cooling periods of 10, 20 and 30 d. The milled material was assessed for the effect of hold time of the blend on the solid dose compression characteristics. The impact of cooling on the processing of the blocks was assessed after 10, 20 and 30 d of cooling. The study suggests that after the hot-melt formed the fenofibrate crystallized independently and a solid solution with croscarmellose sodium was not formed. The age of the blocks determined the hardness of the crystals, changing the processing nature of the granules with respect to compression and powder flow characteristics. The blocks processed after 20 d and beyond produced granules with a characteristic suitable for holding the blend for 14 d in the bin with no impact on flow properties and compressibility of the blend. There was no chipping, capping, sticking or picking observed and a higher compression speed was achieved.
authors.affiliation: a Apotex Inc. , Toronto , ON , Canada.
authors.forename: Rakesh Singh
authors.initials: RS
authors.lastname: Chaudhary
authors.affiliation: a Apotex Inc. , Toronto , ON , Canada.
authors.forename: Edward
authors.initials: E
authors.lastname: Amankwaa
authors.affiliation: a Apotex Inc. , Toronto , ON , Canada.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Kumar
authors.affiliation: a Apotex Inc. , Toronto , ON , Canada.
authors.forename: Tom
authors.initials: T
authors.lastname: Hu
authors.affiliation: a Apotex Inc. , Toronto , ON , Canada.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Chan
authors.affiliation: a Apotex Inc. , Toronto , ON , Canada.
authors.forename: Pradeep
authors.initials: P
authors.lastname: Sanghvi
mesh_terms: D002152:Calorimetry, Differential Scanning; D002266:Carboxymethylcellulose Sodium / Q000737:chemistry*; D003460:Crystallization; D011345:Fenofibrate / Q000737:chemistry*; D000960:Hypolipidemic Agents / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D012995:Solubility; D013607:Tablets; D013678:Technology, Pharmaceutical / Q000379:methods*; D014961:X-Ray Diffraction
chemical_list: D000960:Hypolipidemic Agents; D013607:Tablets; D002266:Carboxymethylcellulose Sodium; D011345:Fenofibrate
keywords: Compression force; compression speed; crystallinity; granules flow properties; hold time; hot-melt; milling process; super cooling