Format

Send to

Choose Destination
Int J Pharm. 2019 Jan 10;554:302-311. doi: 10.1016/j.ijpharm.2018.11.005. Epub 2018 Nov 3.

Formulation of aripiprazole-loaded pH-modulated solid dispersions via hot-melt extrusion technology: In vitro and in vivo studies.

Author information

1
Department of Pharmaceutics and Drug Delivery, The University of Mississippi, University 38677, USA.
2
BASF SE, R&D Product Management Excipients, Ludwigshafen 67056, Germany.
3
BASF Corporation, Tarrytown 10591, USA.
4
College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 41566, Republic of Korea. Electronic address: dkim17@knu.ac.kr.
5
Department of Pharmaceutics and Drug Delivery, The University of Mississippi, University 38677, USA; Pii Center for Pharmaceutical Technology, The University of Mississippi, University 38677, USA. Electronic address: marepka@olemiss.edu.

Abstract

The objective of this study was to formulate aripiprazole (ARI)-loaded pH-modulated solid dispersions (SD) to enhance solubility, dissolution, and bioavailability via hot-melt extrusion (HME) technology. Kollidon® 12 PF (PVP) and succinic acid (SA) were selected after solubility screenings of various polymers and acidifiers. Several formulations, varying in screw speed and drug/polymer/acidifier ratios, were extruded using an 11 mm twin-screw extruder and were investigated for the effect of these variables. Scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and X-ray diffraction (XRD) were used to perform solid-state characterizations of the pure drug and extrudates. The aqueous solubility and dissolution were evaluated for the pure drug and milled extrudates. Among the prepared formulations, N6 was chosen for in vivo absorption studies. Solid-state characterization demonstrated the transformation of the crystalline ARI to an amorphous state in the formulations. Each formulation showed increased solubility and dissolution compared to the drug powder. The oral bioavailability (Cmax and AUC0-12) of N6 was significantly improved when compared to the pure ARI. This novel study not only discusses the incorporation of acidifiers in SDs but also the preparation of SDs using HME technology as effective techniques to improve drug release and bioavailability.

KEYWORDS:

Acidifier; Aripiprazole; Hot-melt extrusion; Oral bioavailability; Pharmacokinetics; Solid dispersion

PMID:
30395959
PMCID:
PMC6312482
[Available on 2020-01-10]
DOI:
10.1016/j.ijpharm.2018.11.005
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center