Calpain inhibitor nanocrystals prepared using Nano Spray Dryer B-90
© Baba and Nishida.; licensee Springer. 2012
Received: 6 June 2012
Accepted: 23 July 2012
Published: 4 August 2012
The Nano Spray Dryer B-90 offers a new, simple, and alternative approach for the production of drug nanocrystals. Among attractive drugs, calpain inhibitor that inhibits programmed cell death ‘apoptosis’ is a candidate for curing apoptosis-mediated intractable diseases such as Alzheimer’s disease and Parkinson’s disease. In this study, the preparation of calpain inhibitor nanocrystals using Nano Spray Dryer B-90 was demonstrated. The particle sizes were controlled by means of selecting mesh aperture sizes. The obtained average particle sizes were in the range of around 300 nm to submicron meter.
Using drug nanoparticles for a drug delivery system has attracted considerable attentions in the field of nanomedicine. Especially, nanoparticles with a drug filling rate of 100% including their amorphous form are called drug nanocrystals. Since a nanocrystal has large surface area compared to a microparticle, the drug nanocrystal has several unique peculiarities such as its increased dissolution velocity, increased saturation velocity, and increased adhesiveness to cell membranes. Additionally, drug nanocrystals are able to deliver large amount of drugs into cells and tissues at a single particle level because of their densely packed crystal structure. Because of their unique physicochemical properties, recently, drug nanocrystals have been considered as a novel type of drug formulation for the drug delivery system.
Several approaches for preparing drug nanocrystals are classified as top-down and bottom-up procedures. For the top-down procedures, techniques of milling, homogenization, and laser ablation are reported. For the bottom-up procedures, techniques of precipitation, chemical vapor, emulsion, and spray dryer are representatives. However, for the top-down procedures, all media milling processes involve high-energy input and are highly inefficient, and a considerable amount of heat is generated in these operations, making processing of thermolabile materials difficult. The contamination of milling balls that should be removed from drug dispersions by some efforts is also a problem, whereas for the bottom-up procedures, the removal of harsh solvents used for the preparation processes of drug dispersions is necessary in the precipitation technique. Since the spray dryer technique takes a facile approach for preparing nanoparticles, which carries out spraying, evaporating the solvent-dissolved drug, and collecting drug particles, numerous drugs can be candidate for nanoparticle preparation in this technique. However, it is difficult for conventional spray dryer techniques to prepare particles with less than 2 μm in size and also to collect their fine particles. In other words, submicrometer-sized particles, i.e., nanoparticles, cannot be obtained using the conventional spray dryer. Recently, an advanced spray dryer technology, Nano Spray Dryer B-90, has been developed by Büchi® (Flawil, Switzerland). The functions of piezoelectrically driven vibrating mesh and electrostatic particle collector realize the successful preparation and collection of nanoparticles. The different mesh aperture sizes create different sizes of nanoparticles. Currently, drug-encapsulated polymeric nanoparticles, protein nanoparticles, and lithium carbonate (Li2CO3) hollow spheres used in lithium batteries have been successfully prepared using Nano Spray Dryer B-90.
Results and discussion
Particle size and size distribution of SNJ-1945 nanocrystals prepared at different experimental conditions
Flow rate (L/min)
Particle size and size distribution (nm)
418 ± 138
994 ± 360
515 ± 197
536 ± 230
We succeeded in preparing size-controlled calpain inhibitor nanocrystals using Nano Spray Dryer B-90. To the best of our knowledge, this is the first time to prepare calpain inhibitor nanocrystals. The particle sizes were associated with the mesh aperture sizes, namely when the mesh aperture sizes decreased, the particle sizes decreased. The concentration of ethanol-dissolved drug solution significantly affected the particle size. Calpain inhibitors will be a promising drug for curing intractable diseases such as Alzheimer’s disease and Parkinson’s disease. Therefore, utilizing the calpain-inhibitor-nanocrystal-based drug delivery system targeting such intractable diseases will be quite attractive topics in the near future, and thus our fundamental findings of preparing calpain inhibitor nanocrystals in this research are noteworthy. We are also investigating the preparation of water dispersion of calpain inhibitor nanocrystals. This nanocrystal water dispersion will act as attractive nanocrystal-based eye drops for the treatment of ophthalmic disorders such as Fuchs’ endothelial dystrophy of the cornea in the near future.
KB is a specially appointed associate professor and KN is a professor and a medical doctor at the Department of Ophthalmology, Osaka University Graduate School of Medicine, Japan.
This study was partially supported by Health and Labour Science Research Grants for Research on Intractable Diseases from the Ministry of Health, Labour and Welfare of Japan and a Challenging Exploratory Research (No. 23650287) and Grant-in-Aid for Young Scientists (A) (No. 24680054) from the Japan Society for the Promotion of Science. We thank Senju Pharmaceutical Co., Ltd. for kindly providing calpain inhibitor SNJ-1945 and Dr. Tadayoshi Egusa for his technical supports of nanocrystal preparation and SEM observation.
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