title: Bioavailability enhancement of a BCS IV compound via an amorphous combination product containing ritonavir.
abstract: OBJECTIVE
  To evaluate the effect of ritonavir (RTV) co-administration on the bioavailability of an amorphous dispersion of acetyl-11-keto-beta-boswellic acid (AKBA) and to develop a pharmaceutically acceptable AKBA-RTV combination tablet.
  
  
  METHODS
  A pharmacokinetic (PK) study in rats was conducted to evaluate the influence of RTV co-administration on the oral bioavailability of an AKBA amorphous dispersion. KinetiSol was utilized to enable production of an improved RTV formulation that facilitated the development of an AKBA-RTV combination tablet. Following in-vitro characterization, the PK performance of the tablets was evaluated in male beagles.
  
  
  RESULTS
  Co-administration of RTV increased oral absorption of AKBA by about fourfold over the AKBA dispersion alone and approximately 24-fold over the pure compound. The improved RTV amorphous dispersion exhibited similar purity and neutral-phase dissolution to Norvir. The AKBA-RTV combination tablets yielded a substantial increase in AKBA's bioavailability in dogs.
  
  
  CONCLUSIONS
  Oral absorption of AKBA is substantially limited by intestinal CYP3A activity and poor aqueous solubility. Consequently, AKBA's oral bioavailability is maximized by administration from a supersaturating formulation in conjunction with a CYP3A inhibitor. The AKBA-RTV combination tablet presented herein represents a breakthrough in the oral delivery of the compound facilitating future use as a drug therapy for broad spectrum cancer treatment.
authors.affiliation: DisperSol Technologies, Georgetown, TX, USA.
authors.forename: Dave A
authors.initials: DA
authors.lastname: Miller
authors.affiliation: DisperSol Technologies, Georgetown, TX, USA.
authors.forename: Justin M
authors.initials: JM
authors.lastname: Keen
authors.affiliation: DisperSol Technologies, Georgetown, TX, USA.|College of Pharmacy, The University of Texas at Austin, Austin, TX, USA.
authors.forename: Chris
authors.initials: C
authors.lastname: Brough
authors.affiliation: DisperSol Technologies, Georgetown, TX, USA.|College of Pharmacy, The University of Texas at Austin, Austin, TX, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Ellenberger
authors.affiliation: DisperSol Technologies, Georgetown, TX, USA.
authors.forename: Marshall
authors.initials: M
authors.lastname: Cisneros
authors.affiliation: College of Pharmacy, The University of Texas at Austin, Austin, TX, USA.
authors.forename: Robert O
authors.initials: RO
authors.lastname: Williams
authors.affiliation: College of Pharmacy, The University of Texas at Austin, Austin, TX, USA.
authors.forename: James W
authors.initials: JW
authors.lastname: McGinity
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D001682:Biological Availability; D001711:Biotransformation; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism*; D065692:Cytochrome P-450 CYP3A Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D004285:Dogs; D004338:Drug Combinations; D004339:Drug Compounding; D007422:Intestines / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D019438:Ritonavir / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D013607:Tablets; D013678:Technology, Pharmaceutical / Q000379:methods; D014315:Triterpenes / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*
chemical_list: C447943:11-keto-boswellic acid; D000972:Antineoplastic Agents, Phytogenic; D065692:Cytochrome P-450 CYP3A Inhibitors; D004338:Drug Combinations; D013607:Tablets; D014315:Triterpenes; D051544:Cytochrome P-450 CYP3A; D019438:Ritonavir
keywords: KinetiSol; acetyl-11-keto-beta-boswellic acid; amorphous dispersion; ritonavir; solubility enhancement