NERDG 2026
Poster 14 Abstract
Development of Spray-Dried Solid Dispersions of Edaravone for Enhanced Oral Delivery
Sanjana Durve, Meghana Mokashi, Zia Uddin Massum, Vivek Gupta
Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Jamaica, NY 11439, USA
Presenting Author: Sanjana Durve
Corresponding Author: Vivek Gupta, [email protected]
Abstract
Edaravone (EDA) (3-methyl-1-phenyl-2-pyrazolin-5-one) is a neuroprotective drug with free radical scavenging properties. EDA was approved for the treatment of Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig's disease, in 2017. Initially approved as an intravenous infusion (RADICAVA®), it was later approved as an oral suspension (RADICAVA ORS®) in 2022.Although oral suspension is a preferred choice, it has some drawbacks, such as poor aqueous and chemical stability, and excipient compatibility issues that limit shelf life.Objective of our research is to enhance the solubility and improve oral bioavailability of EDA by formulating amorphous solid dispersions (ASDs) using spray drying.Solid dispersions were prepared using spray drying technique with lactose monohydrate as the primary carrier, L-leucine to enhance the particulate properties and ascorbic acid as an antioxidant.Formulation was optimized using Box-Behnken design. 5% of Ethanol was used as a co-solvent with 15% drug loading and a solid content of 2%.Spray drying was carried out using Yamato ADL 311S with the operating parameters: inlet temperature: 100° C, dial position 1.34, blower position 10.Drug content and % yield of the resulting powders was evaluated. Solid-state characterization was done using DSC, XRPD followed by In-vitro drug release, 2D safety, and permeability studies on Caco-2 cells.Fifteen formulations were prepared using a Box-Behnken design, 3D surface plots were generated to evaluate the effect of independent factors on each response variable.Optimized formulation exhibited a yield of 62.2 ± 6.0%, drug content of 120.7 ± 1.2 µg/mg, and moisture content of 1.2 ± 0.6%. DSC and XRPD analyses confirmed amorphous nature.In-Vitro dissolution demonstrated more than 85% of the drug released in 2 hours.Safety study in Caco-2 Cell line was performed with single and multiple dose treatment, with qualitative imaging on the multiple dose treatment using the live-dead assay.Caco-2 permeability results indicated that the EDA-spray dried powder showed higher apparent permeability than the plain drug.ASDs were successfully developed using the DoE approach, resulting in an effective alternative solid dosage form.Further studies will investigate SEM analysis for particle morphology, long-term stability of optimized formulation, and clinical modeling to predict the intestinal absorption.
Keywords
Amorphous solid dispersion, solubility enhancement, solid dosage form, spray drying
Poster 14 Abstract
Development of Spray-Dried Solid Dispersions of Edaravone for Enhanced Oral Delivery
Sanjana Durve, Meghana Mokashi, Zia Uddin Massum, Vivek Gupta
Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Jamaica, NY 11439, USA
Presenting Author: Sanjana Durve
Corresponding Author: Vivek Gupta, [email protected]
Abstract
Edaravone (EDA) (3-methyl-1-phenyl-2-pyrazolin-5-one) is a neuroprotective drug with free radical scavenging properties. EDA was approved for the treatment of Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig's disease, in 2017. Initially approved as an intravenous infusion (RADICAVA®), it was later approved as an oral suspension (RADICAVA ORS®) in 2022.Although oral suspension is a preferred choice, it has some drawbacks, such as poor aqueous and chemical stability, and excipient compatibility issues that limit shelf life.Objective of our research is to enhance the solubility and improve oral bioavailability of EDA by formulating amorphous solid dispersions (ASDs) using spray drying.Solid dispersions were prepared using spray drying technique with lactose monohydrate as the primary carrier, L-leucine to enhance the particulate properties and ascorbic acid as an antioxidant.Formulation was optimized using Box-Behnken design. 5% of Ethanol was used as a co-solvent with 15% drug loading and a solid content of 2%.Spray drying was carried out using Yamato ADL 311S with the operating parameters: inlet temperature: 100° C, dial position 1.34, blower position 10.Drug content and % yield of the resulting powders was evaluated. Solid-state characterization was done using DSC, XRPD followed by In-vitro drug release, 2D safety, and permeability studies on Caco-2 cells.Fifteen formulations were prepared using a Box-Behnken design, 3D surface plots were generated to evaluate the effect of independent factors on each response variable.Optimized formulation exhibited a yield of 62.2 ± 6.0%, drug content of 120.7 ± 1.2 µg/mg, and moisture content of 1.2 ± 0.6%. DSC and XRPD analyses confirmed amorphous nature.In-Vitro dissolution demonstrated more than 85% of the drug released in 2 hours.Safety study in Caco-2 Cell line was performed with single and multiple dose treatment, with qualitative imaging on the multiple dose treatment using the live-dead assay.Caco-2 permeability results indicated that the EDA-spray dried powder showed higher apparent permeability than the plain drug.ASDs were successfully developed using the DoE approach, resulting in an effective alternative solid dosage form.Further studies will investigate SEM analysis for particle morphology, long-term stability of optimized formulation, and clinical modeling to predict the intestinal absorption.
Keywords
Amorphous solid dispersion, solubility enhancement, solid dosage form, spray drying
