title: The impact of hot melt extrusion and spray drying on mechanical properties and tableting indices of materials used in pharmaceutical development.
abstract: The impact of melt extrusion (HME) and spray drying (SD) on mechanical properties of hypromellose acetate succinate (HPMCAS), copovidone, and their formulated blends was studied and compared with that of reference excipients. Tensile strength (TS), compression pressure (CP), elastic modulus (E), and dynamic hardness (Hd ) were determined along with Hiestand indices using compacts prepared at a solid fraction of ∼0.85. HPMCAS and copovidone exhibited lower Hd , lower CP, and lower E than the reference excipients and moderate TS. HPMCAS was found to be highly brittle based on brittle fracture index values. The CP was 24% and 61% higher for HPMCAS after SD and HME, respectively, than for unprocessed material along with a higher Hd . Furthermore, the TS of HPMCAS and copovidone decreased upon HME. Upon blending melt-extruded HPMCAS with plastic materials such as microcrystalline cellulose, the TS increased. These results suggest that SD and HME could impact reworkability by reducing deformation of materials and in case of HME, likely by increasing density due to heating and shear stress in a screw extruder. A somewhat similar effect was observed for the dynamic binding index (BId ) of the excipients and formulated blends. Such data can be used to quantitate the impact of processing on mechanical properties of materials during tablet formulation development.
authors: Pharmaceutical & Analytical R & D, Hoffmann-La Roche Inc, Nutley, New Jersey, 07110.
authors: Raman
authors: R
authors: Iyer
authors: Shridhar
authors: S
authors: Hegde
authors: Yu-E
authors: YE
authors: Zhang
authors: James
authors: J
authors: Dinunzio
authors: Dharmendra
authors: D
authors: Singhal
authors: A
authors: A
authors: Malick
authors: Gregory
authors: G
authors: Amidon
mesh_terms: D002482:Cellulose / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004339:Drug Compounding / Q000379:methods*; D005079:Excipients / Q000737:chemistry; D006244:Hardness; D006358:Hot Temperature; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D011759:Pyrrolidines / Q000737:chemistry; D033081:Shear Strength; D013607:Tablets / Q000737:chemistry*; D013718:Tensile Strength; D014753:Vinyl Compounds / Q000737:chemistry
chemical_list: D005079:Excipients; D011759:Pyrrolidines; D013607:Tablets; D014753:Vinyl Compounds; C402301:poly(vinylpyrrolidone-co-vinyl-acetate); C048331:hydroxypropylmethylcellulose acetate succinate; D002482:Cellulose; D008747:Methylcellulose; C109691:microcrystalline cellulose
keywords: compaction; compression; excipients; extrusion; formulation; hardness; hiestand indices; mechanical properties; spray drying; tableting