Background: The objective of this study was to apply Quality by Design (QbD) principles on process
parameter optimization for the development of hybrid delivery system (combination of (SLNs) and In-situ gelling
system) for hydrophilic drug Moxifloxacin Hydrochloride (MOX) to achieve its controlled delivery, which otherwise
may not be possible through single type of technology.
Methods: Risk assessment studies were carried out to identify probable risks influencing CQAs on the product. In
design of experiments (DoE), the process parameters (independent variables) i.e., chiller temperature X1, High
Pressure Homogenization (HPH) pressure X2, and HPH cycles X3 were optimized using a three-factor two level
face-centered central composite design to streamline the influence on three responses, namely encapsulation
efficiency Y1, particle size Y2 and outlet temperature Y3. Independent and dependent variables were analyzed to
establish a full-model second-order polynomial equation. F value is used to confirm the omission of insignificant
parameters/interactions to derive a reduced-model polynomial equation to predict the Y1, Y2 and Y3 for optimized
moxifloxacin in situ gelled nanosuspension.
Results: Desirability plots showed the effects of X1, X2, and X3 on Y1, Y2 and Y3, respectively. The design
space is generated to obtain optimized process parameters viz. chiller temperature (-5°C), HPH pressure 800 –
900 bar and 8 cycles that resulted in nanosuspension with ≈ 500 nm size, encapsulation efficiency >65% and final
formulation temperature <23°C that were necessary to maintain the formulation in a liquid state.
Conclusion: Quality by Design (QbD) approach is recently been encouraged by regulatory bodies to improve the
quality of the finished product. This approach proved to be a useful tool in the development of robust nanosuspension
of highly hydrophilic drugs with improved efficiency. Results indicate that such hybrid gel systems can
be used to control the release of SLNs from application site and prolong their action in a sustained manner.