Limits...
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.

Show MeSH

Related in: MedlinePlus

Dissolution profiles of valsartan–HPMC–surfactant composite nanoparticles prepared by using the SAS process.Notes: pH 1.2 (A); pH 4.0 (B); and pH 6.8 (C) dissolution media. 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
getmorefigures.php?uid=PMC4230178&req=5

f5-ijn-9-5167: Dissolution profiles of valsartan–HPMC–surfactant composite nanoparticles prepared by using the SAS process.Notes: pH 1.2 (A); pH 4.0 (B); and pH 6.8 (C) dissolution media. 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: The in vitro dissolution profiles of valsartan composite nanoparticles were obtained in four different dissolution media (Figure 5). The raw material had a pH-dependent dissolution profile due to its intrinsic pH-dependent solubility. Approximately 4% of the raw material was detected at pH 1.2 within 2 hours. However, approximately 78% of raw material dissolved at pH 6.8 within the same period. The extent and rate of dissolution of valsartan–HPMC nanoparticles increased according to the pH-dependent solubility of valsartan in the order: pH 1.2< pH 4.0< pH 6.8. Interestingly, pH-independent dissolution profiles of valsartan were obtained after the addition of surfactant into valsartan–HPMC nanoparticles owing to micellar solubilization. In particular, the valsartan–HPMC–poloxamer 407 nanoparticles exhibited faster drug release of up to 90% within 10 minutes under all conditions. Previously, it was reported that higher solubilization of valsartan was observed upon using poloxamer 407 than upon using cremophore EL, sodium lauryl sulfate, solutol HS15, TPGS, Ryoto sugar ester L1695, and Gelucire 44/14.5,8 The significant increase in both the dissolution extent and rate of valsartan might be because of the increased supersaturation caused by the amorphous form, and/or the improved wettability of the particles due to surface modification by the surfactant and HPMC. For the in vitro–in vivo correlation study, dissolution profiles were characterized using the dissolution efficiency (DE%) as defined by Khan and Rhodes.27 DE% for valsartan composite nanoparticles was calculated from the area under the dissolution curves at 120 minutes and expressed as a percentage of the area of the rectangle resulting from 100% dissolution within the same time. As expected, the highest DE% was calculated for the valsartan–HPMC–poloxamer 407 nanoparticles (Table 2).


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

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

Dissolution profiles of valsartan–HPMC–surfactant composite nanoparticles prepared by using the SAS process.Notes: pH 1.2 (A); pH 4.0 (B); and pH 6.8 (C) dissolution media. 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

f5-ijn-9-5167: Dissolution profiles of valsartan–HPMC–surfactant composite nanoparticles prepared by using the SAS process.Notes: pH 1.2 (A); pH 4.0 (B); and pH 6.8 (C) dissolution media. 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: The in vitro dissolution profiles of valsartan composite nanoparticles were obtained in four different dissolution media (Figure 5). The raw material had a pH-dependent dissolution profile due to its intrinsic pH-dependent solubility. Approximately 4% of the raw material was detected at pH 1.2 within 2 hours. However, approximately 78% of raw material dissolved at pH 6.8 within the same period. The extent and rate of dissolution of valsartan–HPMC nanoparticles increased according to the pH-dependent solubility of valsartan in the order: pH 1.2< pH 4.0< pH 6.8. Interestingly, pH-independent dissolution profiles of valsartan were obtained after the addition of surfactant into valsartan–HPMC nanoparticles owing to micellar solubilization. In particular, the valsartan–HPMC–poloxamer 407 nanoparticles exhibited faster drug release of up to 90% within 10 minutes under all conditions. Previously, it was reported that higher solubilization of valsartan was observed upon using poloxamer 407 than upon using cremophore EL, sodium lauryl sulfate, solutol HS15, TPGS, Ryoto sugar ester L1695, and Gelucire 44/14.5,8 The significant increase in both the dissolution extent and rate of valsartan might be because of the increased supersaturation caused by the amorphous form, and/or the improved wettability of the particles due to surface modification by the surfactant and HPMC. For the in vitro–in vivo correlation study, dissolution profiles were characterized using the dissolution efficiency (DE%) as defined by Khan and Rhodes.27 DE% for valsartan composite nanoparticles was calculated from the area under the dissolution curves at 120 minutes and expressed as a percentage of the area of the rectangle resulting from 100% dissolution within the same time. As expected, the highest DE% was calculated for the valsartan–HPMC–poloxamer 407 nanoparticles (Table 2).

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