Objective: The article focuses on exploring and comparing two top-down methods, i.e. media milling and microfluidization for the fabrication of nanocrystals of rifampicin (RIF), a poorly water-soluble drug in terms of their potential for generation of stable and efficacious nanocrystals.
Significance: Nanocrystals are often the system of choice for the formulation of poorly water-soluble drugs. The characteristic benefit of nanocrystals lies in their ability to boost the bioavailability of such drugs by enhancing their saturation solubility and dissolution velocity. Nanocrystals can be prepared by either bottom-up or top-down approach. The latter is often preferred due to the feasibility of scale-up and economical nature. Hence, the emphasis is on these methods.
Methods: Stable RIF nanocrystals (RIF NCs) were developed and optimized using media milling and microfluidizer method by incorporating a suitable surfactant/stabilizer. The developed nanocrystals were evaluated for their saturation solubility, in vitro dissolution, solid-state characteristics, morphology, intrinsic dissolution rate, and short-term physical stability.
Results: Both the methods were found to be equally efficient in terms of development of stable RIF NCs, while in terms of processing time and efficacy, microfluidization was found to be advantageous. Amorphization and polymorphic conversion were evident based on the results of solid-state characterization. Furthermore, both formulations exhibited an enhanced solubility and faster dissolution velocity.
Conclusion: Based on the characterization outcomes, it can be concluded that both the top-down technologies could be successfully applied to develop nanocrystals of poorly water-soluble drugs. However, microfluidization was found to outplay media milling in terms of processing time and drug loading.
Keywords: Nanocrystals; dissolution velocity; intrinsic dissolution; media milling; microfluidizer; rifampicin; saturation solubility.