Journal
INTERNATIONAL JOURNAL OF PHARMACEUTICS
Volume 554, Issue -, Pages 302-311Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijpharm.2018.11.005
Keywords
Aripiprazole; Acidifier; Hot-melt extrusion; Solid dispersion; Pharmacokinetics; Oral bioavailability
Categories
Funding
- National Institute of General Medical Sciences (NIGMS), a component of NIH [P20GM104932]
- National Research Foundation (NRF) of South Korea [2018R1D1A1B07050598]
- National Research Foundation of Korea [2018R1D1A1B07050598] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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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 (R) 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 (C-max and AUC(0-12)) 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.
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