Preparation of Hot-Melt Extruded Dosage Form for Enhancing Drugs Absorption Based on Computational Simulation
The aim of this study was to control the dissolution rate and permeability of cilostazol. To enhance the dissolution rate of the active pharmaceutical ingredient (API), hot-melt extrusion (HME) technology was applied to prepare a solid dispersion (SD). To control permeability in the gastrointestinal...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-08-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/12/8/757 |
| _version_ | 1797558863434612736 |
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| author | Sung-Min Choi Sung-Hoon Lee Chin-Yang Kang Jun-Bom Park |
| author_facet | Sung-Min Choi Sung-Hoon Lee Chin-Yang Kang Jun-Bom Park |
| author_sort | Sung-Min Choi |
| collection | DOAJ |
| description | The aim of this study was to control the dissolution rate and permeability of cilostazol. To enhance the dissolution rate of the active pharmaceutical ingredient (API), hot-melt extrusion (HME) technology was applied to prepare a solid dispersion (SD). To control permeability in the gastrointestinal tract regardless of food intake, the HME process was optimized based on physiologically based pharmacokinetic (PBPK) simulation. The extrudates were produced using a laboratory-scale twin-screw hot-melt extruder with co-rotatory screws and a constant feeding rate. Next, for PBPK simulation, parameter-sensitive analysis (PSA) was conducted to determine the optimization approach direction. As demonstrated by the dissolution test, the solubility of extrudate was enhanced comparing cilostazol alone. Based on the PSA analysis, the surfactant induction was a crucial factor in cilostazol absorption; thus, an extrudate with an even distribution of lipids was produced using hot-melt extrusion technology, for inducing the bile salts in the gastrointestinal tract. In vivo experiments with rats demonstrated that the optimized hot-melt extruded formulation was absorbed more rapidly with lower deviation and regardless of the meal consumed when compared to marketed cilostazol formulations. |
| first_indexed | 2024-03-10T17:37:22Z |
| format | Article |
| id | doaj.art-4445c2681b994432a527a816156d946c |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T17:37:22Z |
| publishDate | 2020-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-4445c2681b994432a527a816156d946c2023-11-20T09:48:12ZengMDPI AGPharmaceutics1999-49232020-08-0112875710.3390/pharmaceutics12080757Preparation of Hot-Melt Extruded Dosage Form for Enhancing Drugs Absorption Based on Computational SimulationSung-Min Choi0Sung-Hoon Lee1Chin-Yang Kang2Jun-Bom Park3College of Pharmacy, Sahmyook University, Seoul 01795, KoreaCollege of Pharmacy, Sahmyook University, Seoul 01795, KoreaCollege of Pharmacy, Sahmyook University, Seoul 01795, KoreaCollege of Pharmacy, Sahmyook University, Seoul 01795, KoreaThe aim of this study was to control the dissolution rate and permeability of cilostazol. To enhance the dissolution rate of the active pharmaceutical ingredient (API), hot-melt extrusion (HME) technology was applied to prepare a solid dispersion (SD). To control permeability in the gastrointestinal tract regardless of food intake, the HME process was optimized based on physiologically based pharmacokinetic (PBPK) simulation. The extrudates were produced using a laboratory-scale twin-screw hot-melt extruder with co-rotatory screws and a constant feeding rate. Next, for PBPK simulation, parameter-sensitive analysis (PSA) was conducted to determine the optimization approach direction. As demonstrated by the dissolution test, the solubility of extrudate was enhanced comparing cilostazol alone. Based on the PSA analysis, the surfactant induction was a crucial factor in cilostazol absorption; thus, an extrudate with an even distribution of lipids was produced using hot-melt extrusion technology, for inducing the bile salts in the gastrointestinal tract. In vivo experiments with rats demonstrated that the optimized hot-melt extruded formulation was absorbed more rapidly with lower deviation and regardless of the meal consumed when compared to marketed cilostazol formulations.https://www.mdpi.com/1999-4923/12/8/757hot-melt extrusion technologycilostazoldissolution rate and permeabilityPBPK simulationparameter-sensitive analysis |
| spellingShingle | Sung-Min Choi Sung-Hoon Lee Chin-Yang Kang Jun-Bom Park Preparation of Hot-Melt Extruded Dosage Form for Enhancing Drugs Absorption Based on Computational Simulation Pharmaceutics hot-melt extrusion technology cilostazol dissolution rate and permeability PBPK simulation parameter-sensitive analysis |
| title | Preparation of Hot-Melt Extruded Dosage Form for Enhancing Drugs Absorption Based on Computational Simulation |
| title_full | Preparation of Hot-Melt Extruded Dosage Form for Enhancing Drugs Absorption Based on Computational Simulation |
| title_fullStr | Preparation of Hot-Melt Extruded Dosage Form for Enhancing Drugs Absorption Based on Computational Simulation |
| title_full_unstemmed | Preparation of Hot-Melt Extruded Dosage Form for Enhancing Drugs Absorption Based on Computational Simulation |
| title_short | Preparation of Hot-Melt Extruded Dosage Form for Enhancing Drugs Absorption Based on Computational Simulation |
| title_sort | preparation of hot melt extruded dosage form for enhancing drugs absorption based on computational simulation |
| topic | hot-melt extrusion technology cilostazol dissolution rate and permeability PBPK simulation parameter-sensitive analysis |
| url | https://www.mdpi.com/1999-4923/12/8/757 |
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