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

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.

McFall H ，Sarabu S ，Shankar V ，Bandari S ，Murthy SN ，Kolter K ，Langley N ，Kim DW ，Repka MA ... -  《-》

Preparation, characterization and in vitro/vivo evaluation of tectorigenin solid dispersion with improved dissolution and bioavailability.

Shuai S ，Yue S ，Huang Q ，Wang W ，Yang J ，Lan K ，Ye L ... -  《-》

Soluplus®/TPGS-based solid dispersions prepared by hot-melt extrusion equipped with twin-screw systems for enhancing oral bioavailability of valsartan.

Lee JY ，Kang WS ，Piao J ，Yoon IS ，Kim DD ，Cho HJ ... -  《-》

A New Extrudable Form of Hypromellose: AFFINISOL™ HPMC HME.

Huang S ，O'Donnell KP ，Keen JM ，Rickard MA ，McGinity JW ，Williams RO 3rd ... -  《AAPS PHARMSCITECH》

Fabrication and evaluation of pH-modulated solid dispersion for telmisartan by spray-drying technique.

The present study was undertaken to overcome the problems associated with solubility, dissolution and oral bioavailability of a poorly water-soluble ionizable drug, telmisartan (TMS). For these purposes, a solubility test was carried to select the appropriate formulation composition from various carriers and alkalizers. Solid dispersions (SDs) of TMS were prepared at different drug-to-carrier ratios by the spray-drying technique, and were characterized by dissolution and aqueous solubility studies. The optimum formulation was investigated by dissolution studies at different pH and water media and its solid state characterisations were performed by scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and X-ray diffraction (XRD) studies. In solubility and dissolution tests, all TMS-loaded pH-modulated SDs (pH(M)-SDs) exhibited marked improvement in the dissolution behavior when compared with crystalline TMS powder. The optimum formulation of pH(M)-SD consisted of TMS/PVP (polyvinylpyrrolidone) K30/Na(2)CO(3) at a weight ratio of 2/0.5/3 and showed significant improvement in the aqueous solubility and dissolution rate by approximately 40,000- and 3-fold, respectively, compared to TMS powder. Solid-state characterization revealed the changed in crystallinity of TMS into amorphous state. Furthermore, area under the drug concentration time-curve (AUC) of TMS from the pH(M)-SD increased by 13.4- and 2.1-fold, compared with TMS powder and commercial product, respectively. According to these observations, taken together with dissolution and pharmacokinetic behaviors, pH-modulated SD in the presence of an alkalizer for a poorly water-soluble ionizable drug, TMS, appeared to be efficacious for enhancing its bioavailability.

Marasini N ，Tran TH ，Poudel BK ，Cho HJ ，Choi YK ，Chi SC ，Choi HG ，Yong CS ，Kim JO ... -  《-》