1. Frequency distribution
Scanning Electron Microscopy as a Tool to Identify the Process Variables in Microparticle Formulation
Sasi B Yarragudi1, Greg F Walker1, Andrew N Clarkson2 and Shakila B Rizwan1
1New Zealand’s National School of Pharmacy and 2Department of Anatomy, Otago School of Medical Sciences, University of Otago, Dunedin.
Introduction
To improve the therapeutic concentration of poorly permeable drugs they can be formulated into polymer microparticles.1 Microparticles of specific size aids the transport of drugs across biological membranes and are able to target specific organs. However, optimising these tailor-made microparticles is challenging due to the influence of multiple variables in the formulation process.2
The aim of the current study was to prepare polymeric microparticles with well-defined morphology and size between 10 and 20 μm. Laser scattering (LS), a gold-standard technique in particle size analysis, showed pre-freeze dried microparticles between 10 and 30 μm in size. However, analysis of freeze dried formulations by scanning electron microscopy (SEM) revealed perforated and aggregated microparticles. Subsequent SEM of different formulations identified freeze drying conditions and the polymer properties as possible causes for sub-optimal formulations. The current study signifies the role of SEM in the formulation process.
Results
Particle sizing and optical microscopy of pre freeze dried formulations confirms the formation of microparticles between 10-30m size
Figure 2. Representative optical micrograph of microparticles. Scale bar = 20 m.
Figure 1. Representative graph showing particle size distribution of microparticle by laser scattering technique.
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Particle size (m)
Frequency distribution
SEM of freeze dried formulations reveal aggregated and perforated microparticles A B
Experimental Section
Microparticles were prepared according to the reported methods3 and freeze dried. The resuspended formulations were analysed using LS to determine particle size and distribution. And observed under Optical Microscopy. Freeze dried formulations were analysed by SEM for acceptable size and morphology.
Aims
To determine the effect of process variables in the formulation of polymeric microparticles with well-defined morphology and size between 10 and 20 μm A C
Conclusion
SEM played a critical role in identifying the effects of process variables on microparticle formation. Furthermore, SEM has proved to be an important tool to optimise formulations based on the morphology despite the ‘ideal size’ data obtained from LS. Future studies will include the use of cryoprotectants for optimal freeze drying conditions to formulate microparticles with well defined morphology D B
Figure 3. (A) Scanning electron micrograph of freeze dried microparticles shows extensive particle aggregation. (B) Magnified view of aggregated microparticles
Figure 4. (A) Scanning electron micrograph shows formation of crystal shaped and (C) perforated microparticles . Magnified views are shown in (B) and (D).
References
Casettari L, and Illum L Journal of Controlled Release 190 (2014) 189–200.
Leong, et al. Carbohydrate Polymers 86 (2011) 555–565.
Berthold et al. Journal of Controlled Release 39 (1996)
This work was supported by the Deans Fund (School of Pharmacy). Sasi B Yarragudi was supported by University of Otago Doctoral scholarship.
Acknowledgment