Optimized L-SNEDDS and spray-dried S-SNEDDS using a linked QbD-DM3 rational design for model compound ketoprofen
Vivek D Patel1, Vishal Rathod1, Rahul V Haware1
1Division of Pharmaceutics Sciences, Arnold & Marie Schwartz College of Pharmacy and Health Sciences, The Long Island University, Brooklyn, NY 11201, United States.
International Journal of Pharmaceutics
|December 17, 2022
Summary
This study optimized ketoprofen liquid (L-SNEDDS) and solid (S-SNEDDS) nanoemulsions using a QbD-DM3 strategy. The developed S-SNEDDS demonstrated significantly enhanced drug release and high yield, improving ketoprofen delivery.
Area of Science:
- Pharmaceutical Sciences
- Drug Delivery Systems
- Nanotechnology
Background:
- Ketoprofen (KTF) solubility and bioavailability challenges necessitate advanced drug delivery systems.
- Self-nanoemulsifying drug delivery systems (SNEDDS) offer a promising approach to enhance the solubility and release of poorly soluble drugs.
- Quality by Design (QbD) principles are crucial for developing robust and reproducible pharmaceutical formulations.
Purpose of the Study:
- To design and optimize liquid (L-SNEDDS) and solid (S-SNEDDS) self-nanoemulsifying drug delivery systems for ketoprofen (KTF) using a QbD-DM3 strategy.
- To evaluate the impact of critical process parameters on the yield and loading efficiency of spray-dried S-SNEDDS.
- To characterize the optimized SNEDDS formulations and assess their drug release performance.
Main Methods:
- A Quality by Design - Data mining, modeling, and mechanistic modeling (QbD-DM3) strategy was employed for formulation design.
- Principal Component Analysis (PCA) identified optimal excipients for L-SNEDDS.
- Spray-drying and Box-Behnken design were utilized for S-SNEDDS optimization, evaluating drug concentration, Aerosil® 200 concentration, and feed rate.
- Physicochemical characterization included globule size, polydispersity index, emulsification time, and dissolution studies.
Main Results:
- Optimized L-SNEDDS comprised Capmul® MCM NF, Kolliphor® ELP, and propylene glycol.
- Optimized S-SNEDDS achieved high percent yield (PY) and loading efficiency (LE) with specific drug concentration, Aerosil® 200 concentration, and feed rate.
- The amorphous S-SNEDDS exhibited a 2.37-fold increase in ketoprofen release compared to the pure drug in 0.1 HCl.
- Both L-SNEDDS and S-SNEDDS met quality target product profile criteria, including globule size (<100 nm) and emulsification time (<30 s).
Conclusions:
- The QbD-DM3 approach successfully yielded optimized ketoprofen L-SNEDDS and S-SNEDDS.
- Spray-dried S-SNEDDS significantly enhanced ketoprofen dissolution and demonstrated high yield and loading efficiency.
- These nanoemulsifying systems represent a viable strategy for improving the delivery and therapeutic efficacy of ketoprofen.
