Title:Preparation and Characterization of Stable Nanosuspension for Dissolution Rate Enhancement of Furosemide: A Quality by Design (QbD) Approach
Volume: 15
Issue: 5
Author(s): Akbar L. Marzan, Rahnuma Tabassum, Basarat Jahan, Mehedi H. Asif, Hasan M. Reza, Mohsin Kazi*, Sultan M. Alshehri, Marcel de Matas and Mohammad H. Shariare*
Affiliation:
- Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh,Saudi Arabia
- Department of Pharmaceutical Sciences, North South University, Dhaka,Bangladesh
Keywords:
Antisolvent precipitation, furosemide, nano drug delivery, nanosuspension, QbD, stabilizer.
Abstract: Background: Nano drug delivery systems have the potential to address the challenges of
delivering BCS Class II and IV drugs like furosemide. The purpose of the current study is to prepare
stable nanosuspension and investigate in vitro dissolution performance of the model compound furosemide
using quality by design (QbD) approach.
Methods: Nanosuspension batches with uniform particle size were prepared for furosemide using the
antisolvent precipitation method. A quality by design (Qbd) approach was explored to understand the
impact of process parameters (stirring time, stirring speed, temperature, and injection rate) and material
attributes (drug concentration, stabilizer type, drug: stabilizer ratio, and antisolvent: solvent ratio) on
the quality attributes of furosemide nanosuspension using a full factorial experimental design. Multiple
linear regression and ANOVA were employed to estimate and identify the critical process parameters
and material attributes. Injection rate and stirring time were identified as the most critical process parameters’
affecting the quality attributes of furosemide nanosuspension.
Results: Individual material attributes did not show significant impact on the average particle size of
the nanocrystals, however two-way interactions between material attributes (stabilizer type/drug concentration
and stabilizer type/antisolvent: solvent ratio) significantly affected nanosuspension particle
size distribution. Solid state characterization (PXRD, DSC and SEM) did not exhibit any changes of
physical form during preparation and optimization of the furosemide nanosuspension. Dissolution of
the furosemide nanocrystals in gastric media was significantly higher than that observed for micronized
furosemide suspension and raw furosemide powder. Stability study data suggests that optimized
batches of furosemide nanosuspensions were stable for three months at 4°C and ambient conditions.
Conclusion: The antisolvent precipitation method can produce stable furosemide nanosuspensions with
desirable quality attributes and enhancement of dissolution rate in the gastric medium as compared to
the raw furosemide powder and microsuspension.