title: The role of drug-polymer hydrogen bonding interactions on the molecular mobility and physical stability of nifedipine solid dispersions.
abstract: We investigated the influence of drug-polymer hydrogen bonding interactions on molecular mobility and the physical stability in solid dispersions of nifedipine with each of the polymers polyvinylpyrrolidone (PVP), hydroxypropylmethyl cellulose (HPMCAS), and poly(acrylic acid) (PAA). The drug-polymer interactions were monitored by FT-IR spectroscopy, the molecular mobility was characterized using broadband dielectric spectroscopy, and the crystallization kinetics was evaluated by powder X-ray diffractometry. The strength of drug-polymer hydrogen bonding, the structural relaxation time, and the crystallization kinetics were rank ordered as PVP > HPMCAS > PAA. At a fixed polymer concentration, the fraction of the drug bonded to the polymer was the highest with PVP. Addition of 20% w/w polymer resulted in ∼65-fold increase in the relaxation time in the PVP dispersion and only ∼5-fold increase in HPMCAS dispersion. In the PAA dispersions, there was no evidence of drug-polymer interactions and the polymer addition did not influence the relaxation time. Thus, the strongest drug-polymer hydrogen bonding interactions in PVP solid dispersions translated to the longest structural relaxation times and the highest resistance to drug crystallization.
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, University of Minnesota , Minneapolis, Minnesota 55455, United States.
authors.forename: Khushboo
authors.initials: K
authors.lastname: Kothari
authors.forename: Vishard
authors.initials: V
authors.lastname: Ragoonanan
authors.forename: Raj
authors.initials: R
authors.lastname: Suryanarayanan
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry; D003460:Crystallization; D006859:Hydrogen / Q000737:chemistry; D006860:Hydrogen Bonding; D007700:Kinetics; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D009543:Nifedipine / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D012997:Solvents / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared; D013696:Temperature; D014961:X-Ray Diffraction
chemical_list: D000180:Acrylic Resins; D011108:Polymers; D012997:Solvents; C006903:carbopol 940; C048331:hydroxypropylmethylcellulose acetate succinate; D006859:Hydrogen; D008747:Methylcellulose; D009543:Nifedipine
keywords: FT-IR spectroscopy; crystallization; dielectric spectroscopy; hydroxypropylmethyl cellulose (HPMCAS); molecular mobility; nifedipine; poly(acrylic acid) (PAA); polyvinylpyrrolidone (PVP); solid dispersion