TY - JOUR
T1 - Drug-Carrier Miscibility in Solid Dispersions of Glibenclamide and a Novel Approach to Enhance Its Solubility Using an Effervescent Agent
AU - Pisay, Muralidhar
AU - Bhaskar, K. Vijaya
AU - Mehta, Chetan Hasmukh
AU - Nayak, Usha Yogendra
AU - Koteshwara, Kunnatur Balasundara
AU - Mutalik, Srinivas
N1 - Funding Information:
The authors are thankful to Sun Pharmaceutical Industries Ltd (Ahmedabad, India) for providing glibenclamide, Unitop Chemicals Private Limited (Thane, India) for providing polyethylene glycol (PEG) 1500, and ABITEC Corporation (Mumbai, India) for providing Acconon C-50 as gift samples. The authors also thank Steer Life Private Limited (Bangalore), Manipal College of Pharmaceutical Sciences and Manipal Academy of Higher Education, Manipal for providing the facilities.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - The present research aims to investigate the miscibility, physical stability, solubility, and dissolution rate of a poorly water-soluble glibenclamide (GLB) in solid dispersions (SDs) with hydrophilic carriers like PEG-1500 and PEG-50 hydrogenated palm glycerides (Acconon). Mathematical theories such as Hansen solubility parameters, Flory Huggins theory, Gibbs free energy, and the in silico molecular dynamics simulation study approaches were used to predict the drug-carrier miscibility. To increase the solubility further, the effervescence technique was introduced to the conventional solid dispersions to prepare effervescent solid dispersions (ESD). Solid dispersions (SDs) were prepared by microwave, solvent evaporation, lyophilization, and hot melt extrusion (HME) techniques and tested for different characterization parameters. The theoretical and in silico parameters suggested that GLB would show good miscibility with the selected carriers under certain conditions. Intermolecular hydrogen bonding between the drug and carrier(s) was confirmed by Fourier transform infrared spectroscopy and proton nuclear magnetic resonance spectroscopy. Solid-state characterizations like powder X-ray diffraction, differential scanning calorimetry, and microscopy confirm the amorphous nature of SDs. The addition of the effervescent agent improved the amorphous nature, due to which the solubility and drug release rate was increased. In vitro and ex vivo intestinal absorption studies showed improved flux and permeability than the pure drug, suggesting an enhanced drug delivery. The GLB solubility, dissolution, and stability were greatly enhanced by the SD and ESD technology. Graphical Abstract: [Figure not available: see fulltext.].
AB - The present research aims to investigate the miscibility, physical stability, solubility, and dissolution rate of a poorly water-soluble glibenclamide (GLB) in solid dispersions (SDs) with hydrophilic carriers like PEG-1500 and PEG-50 hydrogenated palm glycerides (Acconon). Mathematical theories such as Hansen solubility parameters, Flory Huggins theory, Gibbs free energy, and the in silico molecular dynamics simulation study approaches were used to predict the drug-carrier miscibility. To increase the solubility further, the effervescence technique was introduced to the conventional solid dispersions to prepare effervescent solid dispersions (ESD). Solid dispersions (SDs) were prepared by microwave, solvent evaporation, lyophilization, and hot melt extrusion (HME) techniques and tested for different characterization parameters. The theoretical and in silico parameters suggested that GLB would show good miscibility with the selected carriers under certain conditions. Intermolecular hydrogen bonding between the drug and carrier(s) was confirmed by Fourier transform infrared spectroscopy and proton nuclear magnetic resonance spectroscopy. Solid-state characterizations like powder X-ray diffraction, differential scanning calorimetry, and microscopy confirm the amorphous nature of SDs. The addition of the effervescent agent improved the amorphous nature, due to which the solubility and drug release rate was increased. In vitro and ex vivo intestinal absorption studies showed improved flux and permeability than the pure drug, suggesting an enhanced drug delivery. The GLB solubility, dissolution, and stability were greatly enhanced by the SD and ESD technology. Graphical Abstract: [Figure not available: see fulltext.].
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U2 - 10.1208/s12249-022-02437-z
DO - 10.1208/s12249-022-02437-z
M3 - Article
C2 - 36253571
AN - SCOPUS:85139991959
SN - 1530-9932
VL - 23
JO - AAPS PharmSciTech
JF - AAPS PharmSciTech
IS - 8
M1 - 284
ER -