Soluplus® (SOL), a graft amorphous copolymer, composed of polyethylene glycol, vinyl acetate and vinylcaprolactam in a ratio of 13: 30: 57, was utilized to prepare solid dispersions containing felodipine (FEL) or ketoconazole (KTZ) using hot-melt extrusion technology. The melting point depression approach was utilized to determine the miscibility and solubility of the model compounds within Soluplus® , of which felodipine demonstrated higher solubility when compared to ketoconazole (14% vs 4.3% w/w) at room temperature (298K). Moreover, the solubility parameters of FEL, KTZ and SOL were calculated as 21.76, 26.51 and 21.64, respectively.
Polarized light microscopy, Fourier transform infrared spectroscopy (FT-IR), Raman microscopy, differential scanning calorimetry (DSC), X-Ray diffraction (XRD), and scanning electron microscopy (SEM) were explored to characterize the FEL-SOL solid dispersions, and FEL was found to be molecularly dispersed in the matrix at a concentration of 10% w/w, which also demonstrated a higher solubility.
A central composite design (CCD) was applied to optimize the processing parameters for KTZ-SOL solid dispersions and the final formulation containing 29.8% drug was extruded at a temperature of 140°C and screw speed of 31 rpm. The robustness of the design was also examined.
A solid dispersion system of paclitaxel (PTX) was also developed to increase the aqueous solubility in order to overcome the side effects of its commercial products Taxol® , which was accomplished with the addition of a non-ionic surfactant, Cremophor® EL. PolyOx™ WSR N-80 (Molecular weight: 200,000 Da) was utilized as the matrix carrier, in which the concentration of PTX was determined as 30%. Various surfactants and solubilizers, including sodium lauryl sulfate (SLS), Lutrol® F68 (F68) and polyethylene glycol (PEG) 3350 were incorporated into the formulation. Of these, PEG 3350 was found to increase the solubility of PTX to 9.29 μg/ml (9-fold); however, the formulation started to precipitate after 2 hours due to the high energy amorphous state of PTX. 5% hydroxypropyl methylcellulose acetate succinate (HPMCAS-LF) successfully postponed the precipitation and maintained the solubility up to 12 hours by forming hydrogen bonds with PTX. This finding was confirmed by FT-IR analysis.
","abstract_html":"<p>Soluplus® (SOL), a graft amorphous copolymer, composed of polyethylene glycol, vinyl acetate and vinylcaprolactam in a ratio of 13: 30: 57, was utilized to prepare solid dispersions containing felodipine (FEL) or ketoconazole (KTZ) using hot-melt extrusion technology. The melting point depression approach was utilized to determine the miscibility and solubility of the model compounds within Soluplus® , of which felodipine demonstrated higher solubility when compared to ketoconazole (14% vs 4.3% w/w) at room temperature (298K). Moreover, the solubility parameters of FEL, KTZ and SOL were calculated as 21.76, 26.51 and 21.64, respectively. </p> <p>Polarized light microscopy, Fourier transform infrared spectroscopy (FT-IR), Raman microscopy, differential scanning calorimetry (DSC), X-Ray diffraction (XRD), and scanning electron microscopy (SEM) were explored to characterize the FEL-SOL solid dispersions, and FEL was found to be molecularly dispersed in the matrix at a concentration of 10% w/w, which also demonstrated a higher solubility. </p> <p>A central composite design (CCD) was applied to optimize the processing parameters for KTZ-SOL solid dispersions and the final formulation containing 29.8% drug was extruded at a temperature of 140°C and screw speed of 31 rpm. The robustness of the design was also examined. </p> <p>A solid dispersion system of paclitaxel (PTX) was also developed to increase the aqueous solubility in order to overcome the side effects of its commercial products Taxol® , which was accomplished with the addition of a non-ionic surfactant, Cremophor® EL. PolyOx™ WSR N-80 (Molecular weight: 200,000 Da) was utilized as the matrix carrier, in which the concentration of PTX was determined as 30%. Various surfactants and solubilizers, including sodium lauryl sulfate (SLS), Lutrol® F68 (F68) and polyethylene glycol (PEG) 3350 were incorporated into the formulation. Of these, PEG 3350 was found to increase the solubility of PTX to 9.29 μg/ml (9-fold); however, the formulation started to precipitate after 2 hours due to the high energy amorphous state of PTX. 5% hydroxypropyl methylcellulose acetate succinate (HPMCAS-LF) successfully postponed the precipitation and maintained the solubility up to 12 hours by forming hydrogen bonds with PTX. This finding was confirmed by FT-IR analysis. </p>","abstract_has_math":false,"creators":["Lu, Jiannan"],"institution":null,"degree_name":"Ph.D. in Pharmaceutical Sciences","degree_level":"Dissertation","degree_discipline":"Biomolecular Sciences","degree_department":null,"school":null,"contributors":["Michael A. Repka","John O'Haver","Seongbong Jo"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2014,"date_issued":"2014-01-01T08:00:00Z","date_published":"2014-01-01T08:00:00Z","updated_at":"2026-07-24T03:06:53Z","subjects":["Design of experiment","Hot melt extrusion","Poorly water soluble compounds","Solid dispersion","Solubility enhancement","Pharmacy and Pharmaceutical Sciences"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://egrove.olemiss.edu/etd/1490","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Michael A. Repka","John O'Haver","Seongbong Jo"]},{"key":"dc:creator","label":"Author","values":["Lu, Jiannan"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2020-01-23T08:00:00Z"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Biomolecular Sciences"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph.D. in Pharmaceutical Sciences"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Design of experiment","Hot melt extrusion","Poorly water soluble compounds","Solid dispersion","Solubility enhancement","Pharmacy and Pharmaceutical Sciences"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://egrove.olemiss.edu/etd/1490"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Soluplus® (SOL), a graft amorphous copolymer, composed of polyethylene glycol, vinyl acetate and vinylcaprolactam in a ratio of 13: 30: 57, was utilized to prepare solid dispersions containing felodipine (FEL) or ketoconazole (KTZ) using hot-melt extrusion technology. The melting point depression approach was utilized to determine the miscibility and solubility of the model compounds within Soluplus® , of which felodipine demonstrated higher solubility when compared to ketoconazole (14% vs 4.3% w/w) at room temperature (298K). Moreover, the solubility parameters of FEL, KTZ and SOL were calculated as 21.76, 26.51 and 21.64, respectively.
Polarized light microscopy, Fourier transform infrared spectroscopy (FT-IR), Raman microscopy, differential scanning calorimetry (DSC), X-Ray diffraction (XRD), and scanning electron microscopy (SEM) were explored to characterize the FEL-SOL solid dispersions, and FEL was found to be molecularly dispersed in the matrix at a concentration of 10% w/w, which also demonstrated a higher solubility.
A central composite design (CCD) was applied to optimize the processing parameters for KTZ-SOL solid dispersions and the final formulation containing 29.8% drug was extruded at a temperature of 140°C and screw speed of 31 rpm. The robustness of the design was also examined.
A solid dispersion system of paclitaxel (PTX) was also developed to increase the aqueous solubility in order to overcome the side effects of its commercial products Taxol® , which was accomplished with the addition of a non-ionic surfactant, Cremophor® EL. PolyOx™ WSR N-80 (Molecular weight: 200,000 Da) was utilized as the matrix carrier, in which the concentration of PTX was determined as 30%. Various surfactants and solubilizers, including sodium lauryl sulfate (SLS), Lutrol® F68 (F68) and polyethylene glycol (PEG) 3350 were incorporated into the formulation. Of these, PEG 3350 was found to increase the solubility of PTX to 9.29 μg/ml (9-fold); however, the formulation started to precipitate after 2 hours due to the high energy amorphous state of PTX. 5% hydroxypropyl methylcellulose acetate succinate (HPMCAS-LF) successfully postponed the precipitation and maintained the solubility up to 12 hours by forming hydrogen bonds with PTX. This finding was confirmed by FT-IR analysis.
"]},{"key":"dc:title","label":"Title","values":["Solubility Enhancement and Precipitation Inhibition of Poorly Water Soluble Compounds Utilizing Hot Melt Extrusion Technology"]}]}],"canonical_facts":{"dc:contributor":["Michael A. Repka","John O'Haver","Seongbong Jo"],"dc:creator":["Lu, Jiannan"],"dc:date.available":["2020-01-23T08:00:00Z"],"dc:description.abstract":["Soluplus® (SOL), a graft amorphous copolymer, composed of polyethylene glycol, vinyl acetate and vinylcaprolactam in a ratio of 13: 30: 57, was utilized to prepare solid dispersions containing felodipine (FEL) or ketoconazole (KTZ) using hot-melt extrusion technology. The melting point depression approach was utilized to determine the miscibility and solubility of the model compounds within Soluplus® , of which felodipine demonstrated higher solubility when compared to ketoconazole (14% vs 4.3% w/w) at room temperature (298K). Moreover, the solubility parameters of FEL, KTZ and SOL were calculated as 21.76, 26.51 and 21.64, respectively.
Polarized light microscopy, Fourier transform infrared spectroscopy (FT-IR), Raman microscopy, differential scanning calorimetry (DSC), X-Ray diffraction (XRD), and scanning electron microscopy (SEM) were explored to characterize the FEL-SOL solid dispersions, and FEL was found to be molecularly dispersed in the matrix at a concentration of 10% w/w, which also demonstrated a higher solubility.
A central composite design (CCD) was applied to optimize the processing parameters for KTZ-SOL solid dispersions and the final formulation containing 29.8% drug was extruded at a temperature of 140°C and screw speed of 31 rpm. The robustness of the design was also examined.
A solid dispersion system of paclitaxel (PTX) was also developed to increase the aqueous solubility in order to overcome the side effects of its commercial products Taxol® , which was accomplished with the addition of a non-ionic surfactant, Cremophor® EL. PolyOx™ WSR N-80 (Molecular weight: 200,000 Da) was utilized as the matrix carrier, in which the concentration of PTX was determined as 30%. Various surfactants and solubilizers, including sodium lauryl sulfate (SLS), Lutrol® F68 (F68) and polyethylene glycol (PEG) 3350 were incorporated into the formulation. Of these, PEG 3350 was found to increase the solubility of PTX to 9.29 μg/ml (9-fold); however, the formulation started to precipitate after 2 hours due to the high energy amorphous state of PTX. 5% hydroxypropyl methylcellulose acetate succinate (HPMCAS-LF) successfully postponed the precipitation and maintained the solubility up to 12 hours by forming hydrogen bonds with PTX. This finding was confirmed by FT-IR analysis.
"],"dc:identifier":["https://egrove.olemiss.edu/etd/1490"],"dc:subject":["Design of experiment","Hot melt extrusion","Poorly water soluble compounds","Solid dispersion","Solubility enhancement","Pharmacy and Pharmaceutical Sciences"],"dc:title":["Solubility Enhancement and Precipitation Inhibition of Poorly Water Soluble Compounds Utilizing Hot Melt Extrusion Technology"],"thesis:degree_discipline":["Biomolecular Sciences"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Ph.D. in Pharmaceutical Sciences"]},"updated_at":"2026-07-24T03:06:53Z"}