Next Article in Journal
Excipient Interactions in Glucagon Dry Powder Inhaler Formulation for Pulmonary Delivery
Next Article in Special Issue
Enhanced Oral Bioavailability of Celecoxib Nanocrystalline Solid Dispersion based on Wet Media Milling Technique: Formulation, Optimization and In Vitro/In Vivo Evaluation
Previous Article in Journal
Wound Healing Property of Curcuminoids as a Microcapsule-Incorporated Cream
Open AccessArticle

Development of a Ternary Solid Dispersion Formulation of LW6 to Improve the In Vivo Activity as a BCRP Inhibitor: Preparation and In Vitro/In Vivo Characterization

College of Pharmacy, Dongguk University-Seoul, Dongguk-ro-32, Ilsan-Donggu, Goyang, Korea
*
Author to whom correspondence should be addressed.
Pharmaceutics 2019, 11(5), 206; https://doi.org/10.3390/pharmaceutics11050206
Received: 15 March 2019 / Revised: 22 April 2019 / Accepted: 24 April 2019 / Published: 1 May 2019
LW6 (3-[2-(4-adamantan-1-yl-phenoxy)-acetylamino]-4-hydroxy-benzoic acid methyl ester) is a potent inhibitor of drug efflux by the breast cancer resistance protein (BCRP). However, its poor aqueous solubility leads to low bioavailability, which currently limits in vivo applications. Therefore, the present study aimed to develop ternary solid dispersion (SD) formulations in order to enhance the aqueous solubility and dissolution rate of LW6. Various SDs of LW6 were prepared using a solvent evaporation method with different drug/excipient ratios. The solubility and dissolution profiles of LW6 in different SDs were examined, and F8-SD which is composed of LW6, poloxamer 407, and povidone K30 at a weight ratio of 1:5:8 was selected as the optimal SD. The structural characteristics of F8-SD were also examined using Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), and scanning electron microscopy (SEM). In the acidic to neutral pH range, F8-SD achieved rapid dissolution with a drug release of 76–81% within 20 min, while the dissolution of pure LW6 was negligible. The XRPD patterns indicated that F8-SD probably enhanced the solubility and dissolution of LW6 by changing the drug crystallinity to an amorphous state, in addition to the solubilizing effect of the hydrophilic carriers. Furthermore, F8-SD significantly improved the oral bioavailability of topotecan, which is a BCRP substrate, in rats. The systemic exposure of topotecan was enhanced approximately 10-fold by the concurrent use of F8-SD. In conclusion, the ternary SD formulation of LW6 with povidone K30 and poloxamer 407 appeared to be effective at improving the dissolution and in vivo effects of LW6 as a BCRP inhibitor. View Full-Text
Keywords: LW6; solid dispersion; BCRP inhibitor; topotecan; bioavailability LW6; solid dispersion; BCRP inhibitor; topotecan; bioavailability
Show Figures

Graphical abstract

MDPI and ACS Style

Bajracharya, R.; Lee, S.H.; Song, J.G.; Kim, M.; Lee, K.; Han, H.-K. Development of a Ternary Solid Dispersion Formulation of LW6 to Improve the In Vivo Activity as a BCRP Inhibitor: Preparation and In Vitro/In Vivo Characterization. Pharmaceutics 2019, 11, 206.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop