title: Investigation and correlation of drug polymer miscibility and molecular interactions by various approaches for the preparation of amorphous solid dispersions.
abstract: Curcumin (CUR) was used as a poorly soluble drug whereas polyvinyl pyrrolidone K90 (PVP), Eudragit EPO (EPO), hydroxypropyl methylcellulose E5 (HPMC) and polyethylene glycol 8000 (PEG) were used as hydrophilic polymers. CUR polymer miscibility was evaluated by solubility parameter, melting point depression and glass transition temperature (Tg) measurements. Molecular interactions between CUR and polymers were determined by Fourier-transform infrared spectroscopy (FTIR) and Raman. Amorphous solid dispersions were prepared with CUR-polymer ratio of 70:30 (w/w) by solvent evaporation technique and were evaluated for dissolution enhancement using USP II method. Physical states of solid dispersions were characterized by X-ray diffraction (XRD) whereas thermal behaviors were investigated using modulated differential scanning calorimetry (MDSC). CUR-EPO system showed good miscibility through all the approaches, whereas immiscibility was found in other CUR-polymer systems. CUR-EPO and CUR-HPMC systems showed significant molecular interactions whereas CUR-PVP and CUR-PEG showed no molecular interactions. All solid dispersions showed significant dissolution enhancement with CUR-EPO showing highest dissolution rate during first 1h whereas CUR-HPMC was effective in maintaining high CUR concentrations for 6h. The study highlights the importance of investigating and correlating drug polymer miscibility and molecular interactions by various approaches for successful formulation of amorphous solid dispersions.
authors: School of Pharmacy & Health Professions, Creighton University, Omaha, NE 68178, United States. Electronic address: fanmeng@creighton.edu.
authors: Fan
authors: F
authors: Meng
authors: School of Pharmacy & Health Professions, Creighton University, Omaha, NE 68178, United States. Electronic address: annetrivino@creighton.edu.
authors: Anne
authors: A
authors: Trivino
authors: School of Pharmacy, MCPHS University, Boston, MA 20115, United States. Electronic address: dev1611@gmail.com.
authors: Dev
authors: D
authors: Prasad
authors: School of Pharmacy & Health Professions, Creighton University, Omaha, NE 68178, United States. Electronic address: harshchauhan@creighton.edu.
authors: Harsh
authors: H
authors: Chauhan
mesh_terms: D003474:Curcumin / Q000737:chemistry*; D004339:Drug Compounding; D008958:Models, Molecular; D011108:Polymers / Q000737:chemistry*; D012995:Solubility; D013818:Thermogravimetry; D044366:Transition Temperature; D014961:X-Ray Diffraction
chemical_list: D011108:Polymers; D003474:Curcumin
keywords: Amorphous; Curcumin; Miscibility; Molecular interactions; Polymers; Solid dispersion