TY - JOUR
T1 - Development of stability-enhanced ternary solid dispersions via combinations of HPMCP and Soluplus® processed by hot melt extrusion
AU - Albadarin, Ahmad B.
AU - Potter, Catherine B.
AU - Davis, Mark T.
AU - Iqbal, Javed
AU - Korde, Sachin
AU - Pagire, Sudhir
AU - Paradkar, Anant
AU - Walker, Gavin
N1 - Publisher Copyright:
© 2017 Elsevier B.V.
PY - 2017/10/30
Y1 - 2017/10/30
N2 - The aim of this study was to evaluate a novel combination of hydroxypropyl methylcellulose phthalate (HPMCP-HP-50) and Soluplus® polymers for enhanced physicochemical stability and solubility of the produced amorphous solid dispersions (ASDs). This was achieved using hot melt extrusion (HME) to convert the crystalline active pharmaceutical ingredient (API) into a more soluble amorphous form within the ternary systems. Itraconazole (ITZ), a Biopharmaceutics Classification System class II (BCS II) API, was selected as the model drug. The ASDs were characterized by Powder X-Ray diffraction (PXRD), Differential Scanning Calorimetry (DSC), Thermogravimetric Analysis (TGA), Fourier Transform Infrared (FTIR) spectroscopy, Solid State Nuclear Magnetic Resonance (ssNMR) and dissolution studies. The data showed that the ASDs were physically and chemically stable at 20 °C and 50% RH over 12 months. PXRD results indicated that the ITZ in the ASDs was in the amorphous state and no recrystallization occurred. DSC scans confirmed that each formulation exhibited a single intermediate glass transition (Tg), around 96.4 °C, indicating that ITZ was completely miscible in the polymeric blends of HPMCP and Soluplus® at up to 30% (w/w) drug loading and that the two polymers were miscible with each other in the presence of ITZ. The FTIR analysis indicated the formation of strong hydrogen bonding between ITZ, HPMCP and Soluplus®. The dissolution end-point of the ASDs was determined to be approximately 10 times greater than that of the crystalline ITZ.
AB - The aim of this study was to evaluate a novel combination of hydroxypropyl methylcellulose phthalate (HPMCP-HP-50) and Soluplus® polymers for enhanced physicochemical stability and solubility of the produced amorphous solid dispersions (ASDs). This was achieved using hot melt extrusion (HME) to convert the crystalline active pharmaceutical ingredient (API) into a more soluble amorphous form within the ternary systems. Itraconazole (ITZ), a Biopharmaceutics Classification System class II (BCS II) API, was selected as the model drug. The ASDs were characterized by Powder X-Ray diffraction (PXRD), Differential Scanning Calorimetry (DSC), Thermogravimetric Analysis (TGA), Fourier Transform Infrared (FTIR) spectroscopy, Solid State Nuclear Magnetic Resonance (ssNMR) and dissolution studies. The data showed that the ASDs were physically and chemically stable at 20 °C and 50% RH over 12 months. PXRD results indicated that the ITZ in the ASDs was in the amorphous state and no recrystallization occurred. DSC scans confirmed that each formulation exhibited a single intermediate glass transition (Tg), around 96.4 °C, indicating that ITZ was completely miscible in the polymeric blends of HPMCP and Soluplus® at up to 30% (w/w) drug loading and that the two polymers were miscible with each other in the presence of ITZ. The FTIR analysis indicated the formation of strong hydrogen bonding between ITZ, HPMCP and Soluplus®. The dissolution end-point of the ASDs was determined to be approximately 10 times greater than that of the crystalline ITZ.
KW - Analytical techniques
KW - Dissolution studies
KW - Enhanced solubility
KW - Itraconazole
KW - Physical stability
UR - http://www.scopus.com/inward/record.url?scp=85029679162&partnerID=8YFLogxK
U2 - 10.1016/j.ijpharm.2017.09.035
DO - 10.1016/j.ijpharm.2017.09.035
M3 - Article
C2 - 28923766
AN - SCOPUS:85029679162
SN - 0378-5173
VL - 532
SP - 603
EP - 611
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
IS - 1
ER -