The Effect of Particle Size on the Absorption of Cyclosporin A Nanosuspensions

Abstract

Background Cyclosporin A (CsA) is a hydrophobic drug widely used as an immunosuppressant and anti-rejection drug in solid organ transplantation. On the market, there are two oral CsA formulations available containing polyoxyethylene castor oil, which can cause serious allergic reactions and nephrotoxicity. In order to eliminate polyoxyethylene castor oil, CsA was formulated into a nanosuspension. This study aimed to design an oral cyclosporin A nanosuspensions (CsA-NSs) and investigate the effect of particle size on absorption of CsA-NSs. Methods CsA-NSs were prepared using a wet bead milling method. Particle size, morphology and crystallinity state of CsA-NSs were characterized. The in vitro dissolution, the intestinal absorption properties and pharmacokinetic study of CsA-NSs were investigated. Results CsA-NSs with sizes of 280 nm, 522 nm and 2967 nm were prepared. The shape of CsA-NSs with smaller size was similar to that of spheres. The crystallinity of CsA in nanocrystals was reduced. The dissolution rate of CsA-NSs (280 nm) was greater than that of CsA-NSs (522 nm) and CsA-NSs (2967 nm). CsA-NSs (280 nm) showed higher absorption rate constants ( K α ) and effective permeability coefficients ( P eff ) of different intestinal segments compared with that of CsA-NSs (522 nm) and CsA-NSs (2967 nm). AUC 0-48h of 280 nm CsA-NSs was about 1.12-fold of that of 522 nm CsA-NSs, and about 1.51-fold of that of 2967 nm CsA-NSs. In particular, the particle size of CsA-NSs was nanoscale, and their bioavailability was bioequivalent with marked self-microemulsion (Sandimmun Neoral ® ). Conclusion It is feasible to prepare CsA-NSs. The dissolution rate, gastrointestinal transport properties and the oral absorption of CsA-NSs were promoted by reducing size. Considering the cost, efficiency and energy consumption, there should be an optimal particle size range in industrial production.

Nanoemulsion Mouthwash Formulation of Bajakah Tampala (Spatholobus littoralis Hassk.) Skin Extract Against Candida albicans

“…The particle size distribution (droplet) test was carried out to determine whether the nanoemulsion preparation of S. littoralis skin mouthwash had a particle size that was by the ideal standard of nanoemulsion particle size, which was <100 nm 37 . It is necessary to know the particle size of the nanoemulsion tested to determine drug absorption and release rate-the smaller the particle size, the faster the absorption process and the resulting pharmacological effects 38 . Tests were only carried out on F2 and F4 because F1 and F3 used the same ingredients, only differing in the concentration of the extract used and expected to have particle sizes that are not much different from F2 and F4 because of the use of the same ingredients.…”

Influence of filtering on the effective concentration and sterility of a 2% cyclosporine ophthalmic solution: a quality improvement perspective

“…In contrast, in a study on the use of a CyA microemulsion formulation of concentration 0.05%, the particle size was smaller than 100 nm, depending on the particle size measurement method [ 17 ]. In addition, several studies have reduced the particle size of CyA by using various formulation techniques [ 13 , 18 , 19 ]. The oily nature of the CyA emulsion has long been recognized as a drawback; thus, studies of an aqueous and clear formulation of CyA have been conducted [ 19 ].…”