Statistical Modeling, Optimization and Characterization of Spray-Dried Solid Self-Microemulsifying Drug Delivery System Using Design of Experiments

Title
Statistical Modeling, Optimization and Characterization of Spray-Dried Solid Self-Microemulsifying Drug Delivery System Using Design of Experiments
Author(s)
김종오용철순마라시니니르말트란탄힙포우델비자이최한곤[최한곤]
Keywords
LIPID-BASED FORMULATIONS; BOX-BEHNKEN DESIGN; DRYING PROCESS; ORAL BIOAVAILABILITY; QUALITY; MICROPARTICLES; NANOPARTICLES; NANOCAPSULES; VARIABLES; COMPLEX
Issue Date
201302
Publisher
PHARMACEUTICAL SOC JAPAN
Citation
CHEMICAL & PHARMACEUTICAL BULLETIN, v.61, no.2, pp.184 - 193
Abstract
The present study systematically and simultaneously investigates the influence of process variables of spray-drying on the properties of solid self-microemulsifying drug delivery system (SMEDDS) using design of experiment (DOE) and optimizes them in order to produce solid-SMEDDS satisfying pre-defined powder quality attributes. Flurbiprofen-loaded liquid-SMEDDS was dispersed in dextran and spray-dried. After preliminary screening, the independent factors selected according to three-factor, three-level Box-Behnken design were inlet temperature (X-1), feed rate (X-2) and carrier concentration (X-3). The responses used to compute the effects of independent factors were moisture content (Y-1), yield (Y-2), drug content (Y-3) and droplet size (Y-4) of the micro-emulsion. SMEDDS powder characteristics such as morphology, thermal behavior, crystallinity and flowability were also considered. Models were developed and model fitting analysis showed an adequate fit for all responses, indicating good predictability. Significant effects of processing parameters on powder characteristics were observed. The spray-drying process parameters were optimized as inlet temperature (134 degrees C), feed rate (5%) and carrier concentration (0.6%) to produce solid-SMEDDS with acceptable moisture content (0.72 +/- 0.02%), yield (58.5 +/- 2.9%), drug content (70.1 +/- 2.7 mg/g) and droplet size (166.8 +/- 13.8 nm). Validation of the optimization process in five batches showed experimental value very close to the predicted one, ensuring the reproducibility of the developed models. Furthermore, optimized parameters resulted a highly crystalline flurbiprofen changed to an amorphous form. In conclusion, this study demonstrated the applicability of the DOE approach for optimizing the process parameters to manufacture solid-SMEDDS with desired quality attributes.
URI
http://hdl.handle.net/YU.REPOSITORY/26592
ISSN
0009-2363
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약학대학 > 약학부 > Articles
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