Bioavailability enhancement of a COX-2 inhibitor, BMS-347070, from a nanocrystalline dispersion prepared by spray-drying.
Spray drying drug with excipients is usually associated with the preparation of microcrystalline or amorphous drug in order to improve bioavailability. It was found that BMS-347070, when spray-dried with Pluronic F127 from acetone or methylene chloride, was dispersed as nanosized crystalline drug within the water-soluble Pluronic matrix. The reduction in drug particle/crystallite size, coupled with wetting by the Pluronic, resulted in a fast-onset formulation with bioavailability comparable to that of a solubilized and a NanoCrystal formulation. For this system, it is theorized that the polyethylene oxide segments of Pluronic crystallize and that the polypropylene oxide segments remain amorphous, providing a size-restricted domain in which the COX-2 drug crystallizes. This results in improved bioavailability while limiting the potential risk of conversion of an amorphous drug to its crystalline state.
Yin
Shawn X
SX
Pharmaceutical Research Institute, Bristol-Myers Squibb Company, One Squibb Drive, P.O. Box 191, New Brunswick, NJ 08903, USA. shawn.yin@bms.com
Franchini
Miriam
M
Chen
Jinling
J
Hsieh
Alice
A
Jen
Sandy
S
Lee
Tu
T
Hussain
Munir
M
Smith
Ronald
R
D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D002851:Chromatography, High Pressure Liquid; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000737:chemistry / Q000493:pharmacokinetics*; D003890:Desiccation; D005079:Excipients; D005663:Furans / Q000737:chemistry / Q000493:pharmacokinetics*; D008698:Mesylates / Q000737:chemistry / Q000493:pharmacokinetics*; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D010316:Particle Size; D020442:Poloxamer / Q000737:chemistry; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D014961:X-Ray Diffraction
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D005079:Excipients; D005663:Furans; D008698:Mesylates; C504079:(Z)-3-((4-bromophenyl)(4-(methylsulfonyl)phenyl)methylene)-4,5-dihydro-2(3H)-furanone; D020442:Poloxamer; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases