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Fabrication and evaluation of valsartan-polymer- surfactant composite nanoparticles by using the supercritical antisolvent process.

Kim MS, Baek IH - Int J Nanomedicine (2014)

Bottom Line: Spherical composite nanoparticles with a mean size smaller than 400 nm, which contained valsartan, were successfully fabricated by using the SAS process.In addition, there was a positive linear correlation between the pharmacokinetic parameters and the in vitro dissolution efficiency.Therefore, the preparation of composite nanoparticles with valsartan-hydroxypropyl methylcellulose and poloxamer 407 by using the SAS process could be an effective formulation strategy for the development of a new dosage form of valsartan with high oral bioavailability.

View Article: PubMed Central - PubMed

Affiliation: College of Pharmacy, Pusan National University, Geumjeong-gu, Busan, Republic of Korea.

ABSTRACT
The aim of this study was to fabricate valsartan composite nanoparticles by using the supercritical antisolvent (SAS) process, and to evaluate the correlation between in vitro dissolution and in vivo pharmacokinetic parameters for the poorly water-soluble drug valsartan. Spherical composite nanoparticles with a mean size smaller than 400 nm, which contained valsartan, were successfully fabricated by using the SAS process. X-ray diffraction and thermal analyses indicated that valsartan was present in an amorphous form within the composite nanoparticles. The in vitro dissolution and oral bioavailability of valsartan were dramatically enhanced by the composite nanoparticles. Valsartan-hydroxypropyl methylcellulose-poloxamer 407 nanoparticles exhibited faster drug release (up to 90% within 10 minutes under all dissolution conditions) and higher oral bioavailability than the raw material, with an approximately 7.2-fold higher maximum plasma concentration. In addition, there was a positive linear correlation between the pharmacokinetic parameters and the in vitro dissolution efficiency. Therefore, the preparation of composite nanoparticles with valsartan-hydroxypropyl methylcellulose and poloxamer 407 by using the SAS process could be an effective formulation strategy for the development of a new dosage form of valsartan with high oral bioavailability.

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Kinetic solubility profiles of valsartan–HPMC–surfactant composite nanoparticles prepared by using the SAS process.Note: Data are expressed as the mean ± standard deviation (n=3).Abbreviations: HPMC, hydroxypropyl methylcellulose; SAS, supercritical antisolvent; TPGS, D-α-Tocopheryl polyethylene glycol 1000 succinate.
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f4-ijn-9-5167: Kinetic solubility profiles of valsartan–HPMC–surfactant composite nanoparticles prepared by using the SAS process.Note: Data are expressed as the mean ± standard deviation (n=3).Abbreviations: HPMC, hydroxypropyl methylcellulose; SAS, supercritical antisolvent; TPGS, D-α-Tocopheryl polyethylene glycol 1000 succinate.

Mentions: Kinetic solubility tests were conducted in simulated gastric fluids at pH 1.2. The valsartan–HPMC nanoparticles had a maximum solubility of 205 μg/mL. As shown in Figure 4, the maximum solubility of valsartan was dramatically increased by the addition of surfactant to valsartan–HPMC nanoparticles. In particular, the solubility of valsartan–HPMC–poloxamer 407 nanoparticles was 999.1 μg/mL, and their concentration at 24 hours was 992.1 μg/mL. The most effective surfactant tested was poloxamer 407, followed by TPGS and Ryoto sugar ester L1695. Poloxamer 407, a hydrophilic ethylene oxide–hydrophobic propylene oxide block copolymer, is an amphiphilic polymer that acts as a surfactant for solubilization via micelle formation, and as a precipitation inhibitor via steric stabilization and/or hydrogen bonding.26 Poorly water-soluble APIs can be incorporated into the hydrophobic propylene oxide core of micelles formed via self-assembly, which would result in the solubilization of poorly water-soluble APIs. In our previous study, higher solubility of valsartan was observed upon using poloxamer 407 than upon using TPGS.8 In addition, the synergistic effect of poloxamer 407 was observed on the supersaturation of valsartan induced from the HPMC composite. However, this topic needs further study using approaches such as a phase solubility analysis.


Fabrication and evaluation of valsartan-polymer- surfactant composite nanoparticles by using the supercritical antisolvent process.

Kim MS, Baek IH - Int J Nanomedicine (2014)

Kinetic solubility profiles of valsartan–HPMC–surfactant composite nanoparticles prepared by using the SAS process.Note: Data are expressed as the mean ± standard deviation (n=3).Abbreviations: HPMC, hydroxypropyl methylcellulose; SAS, supercritical antisolvent; TPGS, D-α-Tocopheryl polyethylene glycol 1000 succinate.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4230178&req=5

f4-ijn-9-5167: Kinetic solubility profiles of valsartan–HPMC–surfactant composite nanoparticles prepared by using the SAS process.Note: Data are expressed as the mean ± standard deviation (n=3).Abbreviations: HPMC, hydroxypropyl methylcellulose; SAS, supercritical antisolvent; TPGS, D-α-Tocopheryl polyethylene glycol 1000 succinate.
Mentions: Kinetic solubility tests were conducted in simulated gastric fluids at pH 1.2. The valsartan–HPMC nanoparticles had a maximum solubility of 205 μg/mL. As shown in Figure 4, the maximum solubility of valsartan was dramatically increased by the addition of surfactant to valsartan–HPMC nanoparticles. In particular, the solubility of valsartan–HPMC–poloxamer 407 nanoparticles was 999.1 μg/mL, and their concentration at 24 hours was 992.1 μg/mL. The most effective surfactant tested was poloxamer 407, followed by TPGS and Ryoto sugar ester L1695. Poloxamer 407, a hydrophilic ethylene oxide–hydrophobic propylene oxide block copolymer, is an amphiphilic polymer that acts as a surfactant for solubilization via micelle formation, and as a precipitation inhibitor via steric stabilization and/or hydrogen bonding.26 Poorly water-soluble APIs can be incorporated into the hydrophobic propylene oxide core of micelles formed via self-assembly, which would result in the solubilization of poorly water-soluble APIs. In our previous study, higher solubility of valsartan was observed upon using poloxamer 407 than upon using TPGS.8 In addition, the synergistic effect of poloxamer 407 was observed on the supersaturation of valsartan induced from the HPMC composite. However, this topic needs further study using approaches such as a phase solubility analysis.

Bottom Line: Spherical composite nanoparticles with a mean size smaller than 400 nm, which contained valsartan, were successfully fabricated by using the SAS process.In addition, there was a positive linear correlation between the pharmacokinetic parameters and the in vitro dissolution efficiency.Therefore, the preparation of composite nanoparticles with valsartan-hydroxypropyl methylcellulose and poloxamer 407 by using the SAS process could be an effective formulation strategy for the development of a new dosage form of valsartan with high oral bioavailability.

View Article: PubMed Central - PubMed

Affiliation: College of Pharmacy, Pusan National University, Geumjeong-gu, Busan, Republic of Korea.

ABSTRACT
The aim of this study was to fabricate valsartan composite nanoparticles by using the supercritical antisolvent (SAS) process, and to evaluate the correlation between in vitro dissolution and in vivo pharmacokinetic parameters for the poorly water-soluble drug valsartan. Spherical composite nanoparticles with a mean size smaller than 400 nm, which contained valsartan, were successfully fabricated by using the SAS process. X-ray diffraction and thermal analyses indicated that valsartan was present in an amorphous form within the composite nanoparticles. The in vitro dissolution and oral bioavailability of valsartan were dramatically enhanced by the composite nanoparticles. Valsartan-hydroxypropyl methylcellulose-poloxamer 407 nanoparticles exhibited faster drug release (up to 90% within 10 minutes under all dissolution conditions) and higher oral bioavailability than the raw material, with an approximately 7.2-fold higher maximum plasma concentration. In addition, there was a positive linear correlation between the pharmacokinetic parameters and the in vitro dissolution efficiency. Therefore, the preparation of composite nanoparticles with valsartan-hydroxypropyl methylcellulose and poloxamer 407 by using the SAS process could be an effective formulation strategy for the development of a new dosage form of valsartan with high oral bioavailability.

Show MeSH
Related in: MedlinePlus