title: Improved Release of Celecoxib from High Drug Loading Amorphous Solid Dispersions Formulated with Polyacrylic Acid and Cellulose Derivatives.
abstract: Amorphous solid dispersions (ASDs) have been extensively exploited as a strategy for improving the dissolution performance of poorly water-soluble drugs. However, factors underpinning the observed dissolution profiles are not clearly understood, and the choice of polymeric carriers is largely empirical. In the current study, the dissolution performance of a high drug loading ASD containing the poorly water-soluble, anti-inflammatory agent, celecoxib, was optimized by using binary polymers combinations. Polyacrylic acid (PAA), a highly water-soluble polymer, was used to substantially increase the dissolution rate of the drug, while hydroxypropyl methyl cellulose (HPMC) or HPMC acetate succinate (HPMCAS) were added to stabilize the solid amorphous matrix against crystallization upon hydration, as well as to maintain supersaturation. Quantitative measurements of the impact of the polymers on the solution nucleation and growth rates of celecoxib revealed that, while the cellulose derivatives are effective nucleation inhibitors, it is more difficult to completely prevent crystal growth in solutions containing seed crystals, in particular at high supersaturations. Therefore, it is critical to prevent the formation of crystals in the dissolving matrix during dissolution. By using certain ratios of HPMC and PAA, both rapid release as well as crystallization inhibition could be achieved, even at high drug loadings. Utilizing combinations of polymers may therefore be useful to tailor release profiles while providing optimized crystallization inhibition.
authors.affiliation: Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University , West Lafayette, Indiana 47907, United States.
authors.forename: Tian
authors.initials: T
authors.lastname: Xie
authors.affiliation: Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University , West Lafayette, Indiana 47907, United States.
authors.forename: Lynne S
authors.initials: LS
authors.lastname: Taylor
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry*; D000068579:Celecoxib / Q000737:chemistry* / Q000378:metabolism*; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D004339:Drug Compounding; D004355:Drug Stability; D065347:Hypromellose Derivatives / Q000737:chemistry*; D008747:Methylcellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D012995:Solubility
chemical_list: D000180:Acrylic Resins; D004337:Drug Carriers; D011108:Polymers; D065347:Hypromellose Derivatives; C006903:carbopol 940; C048331:hydroxypropylmethylcellulose acetate succinate; D008747:Methylcellulose; D000068579:Celecoxib
keywords: amorphous solid dispersions; crystallization; drug release; miscibility; supersaturation