TY - JOUR
T1 - Formulation and characterization of ternary amorphous solid dispersions of a highly potent anti-tubercular agent and curcumin
AU - Borde, Shambhavi
AU - Hegde, Pooja
AU - Prathipati, Pavan
AU - North, Jeffrey
AU - Kumari, Dunesh
AU - Chauhan, Harsh
N1 - Funding Information:
The author wishes to acknowledge Creighton University , Omaha, for funding and the use of instruments in completing this project. The XRD experiments were performed in part in the Nebraska Nanoscale Facility: National Nanotechnology Coordinated Infrastructure and the Nebraska Center for Materials and Nanoscience, which are supported by the National Science Foundation under Award NNCI-1542182 , and the Nebraska Research Initiative .
Publisher Copyright:
© 2021 Elsevier B.V.
PY - 2021/8
Y1 - 2021/8
N2 - The enhancement of aqueous solubility of poorly water-soluble drugs is a challenge. Additional hurdle is to enhance the solubility of more than one drugs in same formulation for the combination therapy. This research paper presents the development of novel amorphous ternary (drug-drug-hydrophilic polymer) solid dispersions to simultaneously enhance the aqueous solubility and stability of two poorly soluble drugs. The ternary amorphous solid dispersions in the study contains the combination of a highly potent and novel anti-tubercular agent, Indole2-carboxamide derivative (North 2) and anti-oxidant, curcumin (CUR). Binary and ternary amorphous dispersions of North 2 and CUR were prepared using hydrophilic polymers, namely polyvinylpyrrolidone (PVP), Eudragit EPO® (EPO), and hydroxypropyl methylcellulose (HPMC), at 1:1 w/w (for binary solid dispersions) and at 1:1:2 w/w/w (for ternary solid dispersions) ratios. Differential scanning calorimetry (DSC) studies showed that North 2 has high crystallization tendency and formed an amorphous binary solid dispersion with only EPO, whereas CUR was characterized as low crystallization tendency compound and formed amorphous binary solid dispersions with EPO, PVP, and HPMC. All the three polymers formed amorphous ternary solid dispersions at 1:1:2 w/w/w ratios. Fourier transform infrared spectroscopy (FTIR) data showed significant peak shifts in both binary and ternary dispersions of North 2/CUR indicating molecular interactions. These interactions mainly involved the carbonyl group of both compounds, indole –NH of North 2 and phenolic –OH of CUR with the polymer chain. These interactions were confirmed by solution NMR and molecular modeling studies. In dissolution studies, out of the three hydrophilic polymers, EPO showed maximum solubility enhancement with and increased solubility by 55 and 59 times for North 2 and CUR, respectively, within 12 h. XRD stability data of the ternary solid dispersions showed that they were stable over 90 days at room temperature. The aqueous solubility of North 2 and curcumin was enhanced successfully with 50% loading of the drugs. Hence, this study shows the potential of designing ternary dispersions to achieve the solubility enhancement of a combination of poorly soluble drugs by utilizing a molecularly interacting hydrophilic polymer.
AB - The enhancement of aqueous solubility of poorly water-soluble drugs is a challenge. Additional hurdle is to enhance the solubility of more than one drugs in same formulation for the combination therapy. This research paper presents the development of novel amorphous ternary (drug-drug-hydrophilic polymer) solid dispersions to simultaneously enhance the aqueous solubility and stability of two poorly soluble drugs. The ternary amorphous solid dispersions in the study contains the combination of a highly potent and novel anti-tubercular agent, Indole2-carboxamide derivative (North 2) and anti-oxidant, curcumin (CUR). Binary and ternary amorphous dispersions of North 2 and CUR were prepared using hydrophilic polymers, namely polyvinylpyrrolidone (PVP), Eudragit EPO® (EPO), and hydroxypropyl methylcellulose (HPMC), at 1:1 w/w (for binary solid dispersions) and at 1:1:2 w/w/w (for ternary solid dispersions) ratios. Differential scanning calorimetry (DSC) studies showed that North 2 has high crystallization tendency and formed an amorphous binary solid dispersion with only EPO, whereas CUR was characterized as low crystallization tendency compound and formed amorphous binary solid dispersions with EPO, PVP, and HPMC. All the three polymers formed amorphous ternary solid dispersions at 1:1:2 w/w/w ratios. Fourier transform infrared spectroscopy (FTIR) data showed significant peak shifts in both binary and ternary dispersions of North 2/CUR indicating molecular interactions. These interactions mainly involved the carbonyl group of both compounds, indole –NH of North 2 and phenolic –OH of CUR with the polymer chain. These interactions were confirmed by solution NMR and molecular modeling studies. In dissolution studies, out of the three hydrophilic polymers, EPO showed maximum solubility enhancement with and increased solubility by 55 and 59 times for North 2 and CUR, respectively, within 12 h. XRD stability data of the ternary solid dispersions showed that they were stable over 90 days at room temperature. The aqueous solubility of North 2 and curcumin was enhanced successfully with 50% loading of the drugs. Hence, this study shows the potential of designing ternary dispersions to achieve the solubility enhancement of a combination of poorly soluble drugs by utilizing a molecularly interacting hydrophilic polymer.
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U2 - 10.1016/j.jddst.2021.102564
DO - 10.1016/j.jddst.2021.102564
M3 - Article
AN - SCOPUS:85106856982
VL - 64
JO - Journal of Drug Delivery Science and Technology
JF - Journal of Drug Delivery Science and Technology
SN - 1773-2247
M1 - 102564
ER -