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Drug Dev Ind Pharm. 2019 Jul;45(7):1140-1148. doi: 10.1080/03639045.2019.1600533. Epub 2019 Apr 21.

Preparation, characterization and ex vivo-in vivo assessment of candesartan cilexetil nanocrystals via solid dispersion technique using an alkaline esterase activator carrier.

Author information

1
a Pharonia Pharmaceutical Industries , Alexandria , Egypt.
2
b Department of Pharmaceutics, Faculty of Pharmacy , Alexandria University , Alexandria , Egypt.
3
c Department of Pharmaceutics and Pharmacy Practice , Oman College of Health Sciences , Muscat , Oman.

Abstract

The objective of this study was to improve candesartan cilexetil (CC) efficacy by formulating nanocrystals via solid dispersion (SD) technique using tromethamine (Tris). SD was prepared by solvent evaporation at different drug carrier ratios, evaluated for particle size, vitro dissolution studies, TEM, FTIR, and X-ray powder diffraction. Ex vivo, in vivo pharmacokinetic parameters were conducted on selected formulae compared to drug suspension and marketed product. Size analysis demonstrated formation of particles in the nanorange lower than 300 nm. A burst drug release followed by an improved dissolution was observed indicating instant formation of nanocrystals along with amorphization as confirmed by X-ray diffraction. FTIR studies suggested the absence of chemical interaction between Tris and CC. TEM revealed formation of irregular oval nanoparticles. SD-1:5 has higher apparent permeability coefficient compared to CC suspension. Furthermore, the pharmacokinetic results proved the ability of the formed nanoparticles to enhance the efficacy of CC compared to drug suspension and marketed product. In conclusion, using of Tris as alkaline esterase activator carrier could be a promising tool to bypass the controversial effect of esterase enzymes that may be a source for inter-individual variations affecting ester prodrug candidates' efficacy.

KEYWORDS:

Candesartan; bioavailability; candesartan cilexetil; prodrug; solid dispersion; tromethamine

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