Cocrystalization and Simultaneous Agglomeration Using Hot Melt Extrusion

• Published in: Pharmaceutical research Vol. 27; no. 12; pp. 2725 - 2733
• Main Authors: Dhumal, Ravindra S, Kelly, Adrian L, York, Peter, Coates, Phil D, Paradkar, Anant
• Format: Journal Article
• Language: English
• Published: Boston Boston : Springer US 01-12-2010; Springer US; Springer; Springer Nature B.V
• Subjects: Analgesics; Biochemistry; Biological and medical sciences; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Calorimetry, Differential Scanning; Chromatography, High Pressure Liquid; cocrystals; Crystallization; General pharmacology; hot melt extrusion; Hot Temperature; ibuprofen; Medical Law; Medical sciences; Microscopy, Electron, Scanning; Pharmaceutical Preparations - chemistry; Pharmaceutical sciences; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Pharmacology/Toxicology; Pharmacy; Research Paper; Solubility; Spectrophotometry, Ultraviolet; thermo-mechanical process; X-Ray Diffraction; ibuprofen; thermo-mechanical process; cocrystals; hot melt extrusion; Prostaglandin-endoperoxide synthase; Hot melt; Pharmaceutical technology; Enzyme; Enzyme inhibitor; Agglomeration; Process; Non steroidal antiinflammatory agent; Ibuprofen; Arylpropionic acid derivatives; Extrusion; Oxidoreductases
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-010-0273-9

Purpose To explore hot melt extrusion (HME) as a scalable, solvent-free, continuous technology to design cocrystals in agglomerated form. Methods Cocrystal agglomerates of ibuprofen and nicotinamide in 1:1 ratio were produced using HME at different barrel temperature profiles, screw speeds, and screw configurations. Product was characterized for crystallinity by XRPD and DSC, while the morphology was determined by SEM. Dissolution rate and tabletting properties were compared with ibuprofen. Results Process parameters significantly affected the extent of cocrystallization which improved with temperature, applied shear and residence time. Processing above eutectic point was required for cocrystallization to occur, and it improved with mixing intensity by changing screw configuration. Product was in the form of spherical agglomerates, which showed directly compressible nature with enhanced dissolution rate compared to ibuprofen. This marks an important advantage over the conventional techniques, as it negates the need for further size modification steps. Conclusions A single-step, scalable, solvent-free, continuous cocrystallization and agglomeration technology was developed using HME, offering flexibility for tailoring the cocrystal purity. HME being an established technology readily addresses the regulatory demand of quality by design (QbD) and process analytical technology (PAT), offering high potential for pharmaceuticals.