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J Pharm Pharmacol. 2016 May;68(5):678-91. doi: 10.1111/jphp.12478. Epub 2015 Oct 10.

Bioavailability enhancement of a BCS IV compound via an amorphous combination product containing ritonavir.

Author information

1
DisperSol Technologies, Georgetown, TX, USA.
2
College of Pharmacy, The University of Texas at Austin, Austin, TX, USA.

Abstract

OBJECTIVES:

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.

KEY FINDINGS:

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.

KEYWORDS:

KinetiSol; acetyl-11-keto-beta-boswellic acid; amorphous dispersion; ritonavir; solubility enhancement

PMID:
26454138
DOI:
10.1111/jphp.12478
[Indexed for MEDLINE]

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