Increased dissolution rate and bioavailability through comicronization with microcrystalline cellulose.
Micronization is a commonly used enabling technology to improve the bioavailability of compounds where absorption is dissolution rate limited. However, decreasing particle size often results in increased Van der Waals' interactions and electrostatic attraction between particles. This causes agglomeration of particles, thereby compromising the increase in surface area gained by micronization. Comicronization with excipients has been reported to offer significant advantages over neat micronization. The present work describes the comicronization of a model compound CI-1040 at a high drug load that shows an increase in the dissolution rate and bioavailability in male Wistar rats. Physicochemical characterization of the comicronized and neat micronized material is presented to help explain the in-vitro and in-vivo data.
Spence
Julie K
JK
Pharmaceutical Research and Development, World Wide Pharmaceutical Sciences, Pfizer Global Research and Development-Michigan Laboratories, Ann Arbor, Michigan, USA. Julie.Spence@Pfizer.com
Bhattachar
Shobha N
SN
Wesley
James A
JA
Martin
Peter J
PJ
Babu
Suresh R
SR
D000818:Animals; D001549:Benzamides / Q000737:chemistry* / Q000493:pharmacokinetics*; D001682:Biological Availability; D002482:Cellulose / Q000737:chemistry*; D005079:Excipients / Q000737:chemistry*; D008297:Male; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods*; D014961:X-Ray Diffraction
C120227:2-(2-chloro-4-iodophenylamino)-N-cyclopropylmethoxy-3,4-difluorobenzamide; D001549:Benzamides; D005079:Excipients; D002482:Cellulose; C109691:microcrystalline cellulose