title: Hydroxypropyl cellulose stabilizes amorphous solid dispersions of the poorly water soluble drug felodipine.
abstract: Overcoming the low oral bioavailability of many drugs due to their poor aqueous solubility is one of the major challenges in the pharmaceutical industry. The production of amorphous solid dispersions (ASDs) of these drugs using hydrophilic polymers may significantly improve their solubility. However, their storage stability and the stability of their supersaturated solutions in the gastrointestinal tract upon administration are unsolved problems. We have investigated the potential of a low viscosity grade of a cellulosic polymer, hydroxypropyl cellulose (HPC-SSL), and compared it with a commonly used vinyl polymer, polyvinylpyrrolidone vinyl acetate (PVP-VA), for stabilizing the ASDs of a poorly water soluble drug, felodipine. The ASDs were produced using hot melt mixing and stored under standard and accelerated stability conditions. The ASDs were characterized using differential scanning calorimetry, powder X-ray diffraction, and Fourier transform infrared spectroscopy. Drug dissolution and partitioning rates were evaluated using single- and biphasic dissolution studies. The ASDs displayed superior drug dissolution and partitioning as compared to the pure crystalline drug, which might be attributed to the formation of a drug-polymer molecular dispersion, amorphous conversion of the drug, and drug-polymer hydrogen bonding interactions. Late phase separation and early re-crystallization occurred at lower and higher storage temperatures, respectively, for HPC-SSL ASDs, whereas early phase separation, even at low storage temperatures, was noted for PVP-VA ASDs. Consequently, the partitioning rates for ASDs dispersed in HPC-SSL were greater than those of PVP-VA at lower and room temperature storage, whereas the performance of both of the ASDs was similar when stored at higher temperatures.
authors.affiliation: Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI, USA; Department of Chemical Engineering, College of Engineering, University of Rhode Island, Kingston, RI, USA.
authors.forename: Ashish L
authors.initials: AL
authors.lastname: Sarode
authors.affiliation: Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI, USA.
authors.forename: Swapnil A
authors.initials: SA
authors.lastname: Malekar
authors.affiliation: Nisso America Inc., New York, NY, USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: Cote
authors.affiliation: Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI, USA; Department of Chemical Engineering, College of Engineering, University of Rhode Island, Kingston, RI, USA. Electronic address: DWorthen@ds.uri.edu.
authors.forename: David R
authors.initials: DR
authors.lastname: Worthen
mesh_terms: D002152:Calorimetry, Differential Scanning; D002482:Cellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D003460:Crystallization; D004339:Drug Compounding / Q000379:methods; D004355:Drug Stability; D015736:Felodipine / Q000737:chemistry*; D011205:Povidone / Q000737:chemistry; D012995:Solubility; D012996:Solutions; D017550:Spectroscopy, Fourier Transform Infrared; D013696:Temperature; D014961:X-Ray Diffraction
chemical_list: D012996:Solutions; D002482:Cellulose; C008079:hydroxypropylcellulose; D011205:Povidone; D015736:Felodipine
keywords: Amorphous solid dispersion; Hot melt extrusion; Hydroxypropyl cellulose; Interaction; Stability; Supersaturation