Haste Makes Waste: The Interplay Between Dissolution and Precipitation of Supersaturating Formulations.
Contrary to the early philosophy of supersaturating formulation design for oral solid dosage forms, current evidence shows that an exceedingly high rate of supersaturation generation could result in a suboptimal in vitro dissolution profile and subsequently could reduce the in vivo oral bioavailability of amorphous solid dispersions. In this commentary, we outline recent research efforts on the specific effects of the rate and extent of supersaturation generation on the overall kinetic solubility profiles of supersaturating formulations. Additional insights into an appropriate definition of sink versus nonsink dissolution conditions and the solubility advantage of amorphous pharmaceuticals are also highlighted. The interplay between dissolution and precipitation kinetics should be carefully considered in designing a suitable supersaturating formulation to best improve the dissolution behavior and oral bioavailability of poorly water-soluble drugs.
Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, 144 College Street, Toronto, Ontario, M5S 3M2, Canada.|Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, Maryland, 20993, USA.
Dajun D
DD
Sun
Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, 144 College Street, Toronto, Ontario, M5S 3M2, Canada. ping.lee@utoronto.ca.
Ping I
http://orcid.org/0000-0002-3777-8022
PI
Lee
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D011232:Chemical Precipitation; D002626:Chemistry, Pharmaceutical / Q000379:methods* / Q000592:standards; D006801:Humans; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism*; D012995:Solubility; D013997:Time Factors
D004364:Pharmaceutical Preparations
amorphous formulation; kinetic solubility; nonsink dissolution testing; poorly water-soluble drug; supersaturation rate