Abstract
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.
Highlights
It is well known that solubility and permeability of a drug in the gastrointestinal tract is very crucial to exert its effect following oral administration
The dissolution results demonstrated that cilostazol exhibited the most enhanced drug release behavior at a processing temperature (HME) of 120 ◦C
As the processing temperature increased to 160 and 200 ◦C, lower drug release patterns were observed. This appeared to be due to the relatively low glass transition temperatures of Kollidon® and Soluplus®, indicating that when hot melt extrusion (HME) occurred in the presence of Kollidon® it increased the stability of the drug through the lowering of the process temperature
Summary
It is well known that solubility and permeability of a drug in the gastrointestinal tract is very crucial to exert its effect following oral administration. Numerous studies on the solubilization of poorly water-soluble drugs are ongoing. Hot melt extrusion (HME) technology was applied to prepare SD, because it does not pose any toxicity problems associated with residual solvent. This technology can be called environmentally friendly [4,5,6]. HME is a well-known manufacturing technique used to enhance the dissolution rate of poorly water-soluble drugs, converting drugs into their amorphous forms at high temperature and pressure, and evenly dispersing the active pharmaceutical ingredient (API) into the hydrophilic polymer [7,8,9,10]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
