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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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Plasma concentration-time profile of valsartan in rats after oral administration of the raw material and valsartan composite nanoparticles prepared by using the SAS process.Note: Data are expressed as the mean ± standard deviation (n=5).Abbreviations: HPMC, hydroxypropyl methylcellulose; SAS, supercritical antisolvent; TPGS, D-α-Tocopheryl polyethylene glycol 1000 succinate.
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f6-ijn-9-5167: Plasma concentration-time profile of valsartan in rats after oral administration of the raw material and valsartan composite nanoparticles prepared by using the SAS process.Note: Data are expressed as the mean ± standard deviation (n=5).Abbreviations: HPMC, hydroxypropyl methylcellulose; SAS, supercritical antisolvent; TPGS, D-α-Tocopheryl polyethylene glycol 1000 succinate.

Mentions: The pharmacokinetic study of valsartan composite nanoparticles and raw material was conducted in rats. The oral absorption of valsartan from the composite nanoparticles was dramatically higher than that of the raw material, as shown in the plasma concentration-time curves of valsartan after oral administration (Figure 6). In particular, the valsartan–HPMC–poloxamer 407 nanoparticles exhibited higher oral bioavailability than that of the raw material, with approximately 7.2- and 4.6-fold higher Cmax and AUC0→24 h, respectively (Table 3). In addition, the AUC0→24 h of valsartan increased in the order: raw material < HPMC nanoparticles < HPMC–Ryoto sugar ester L1695 nanoparticles = HPMC–TPGS nanoparticles < HPMC–poloxamer 407 nanoparticles.


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

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

Plasma concentration-time profile of valsartan in rats after oral administration of the raw material and valsartan composite nanoparticles prepared by using the SAS process.Note: Data are expressed as the mean ± standard deviation (n=5).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

f6-ijn-9-5167: Plasma concentration-time profile of valsartan in rats after oral administration of the raw material and valsartan composite nanoparticles prepared by using the SAS process.Note: Data are expressed as the mean ± standard deviation (n=5).Abbreviations: HPMC, hydroxypropyl methylcellulose; SAS, supercritical antisolvent; TPGS, D-α-Tocopheryl polyethylene glycol 1000 succinate.
Mentions: The pharmacokinetic study of valsartan composite nanoparticles and raw material was conducted in rats. The oral absorption of valsartan from the composite nanoparticles was dramatically higher than that of the raw material, as shown in the plasma concentration-time curves of valsartan after oral administration (Figure 6). In particular, the valsartan–HPMC–poloxamer 407 nanoparticles exhibited higher oral bioavailability than that of the raw material, with approximately 7.2- and 4.6-fold higher Cmax and AUC0→24 h, respectively (Table 3). In addition, the AUC0→24 h of valsartan increased in the order: raw material < HPMC nanoparticles < HPMC–Ryoto sugar ester L1695 nanoparticles = HPMC–TPGS nanoparticles < HPMC–poloxamer 407 nanoparticles.

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