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

Scanning electron micrographs of valsartan–HPMC–surfactant composite nanoparticles prepared by using the SAS process.Notes: (A) Valsartan–HPMC; (B) valsartan–HPMC–poloxamer 407; (C) valsartan–HPMC–Ryoto sugar ester L1695; and (D) valsartan–HPMC–TPGS.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

f2-ijn-9-5167: Scanning electron micrographs of valsartan–HPMC–surfactant composite nanoparticles prepared by using the SAS process.Notes: (A) Valsartan–HPMC; (B) valsartan–HPMC–poloxamer 407; (C) valsartan–HPMC–Ryoto sugar ester L1695; and (D) valsartan–HPMC–TPGS.Abbreviations: HPMC, hydroxypropyl methylcellulose; SAS, supercritical antisolvent; TPGS, D-α-Tocopheryl polyethylene glycol 1000 succinate.

Mentions: Ternary compositions, containing polymer in addition to surfactant, may provide effective surface modification and solubilization, resulting in enhanced supersaturation, dissolution rate, and oral absorption of valsartan. However, high amounts of surfactant can induce gastrointestinal tract irritation. Here, the valsartan–HPMC–surfactant composite nanoparticles were fabricated at a 20% drug:70% HPMC:10% surfactant (w/w/w) ratio. As shown in Table 1, the size of valsartan composite nanoparticles increased after the addition of surfactants such as poloxamer 407, Ryoto sugar ester L1695, and TPGS. Valsartan–HPMC–Ryoto sugar ester L1695 particles showed some aggregation and had a specific surface area of 25.2 m2/g (Figure 2). The fusion and aggregation of nanoparticles might be due to the low melting temperature of surfactants, as previously reported.10,18 In fact, the melting points of the used surfactants were below 55°C. However, the mean size of all valsartan–HPMC–surfactant nanoparticles was less than 800 nm. The DSC curves and PXRD patterns of composite nanoparticles did not show the characteristic endothermic melting peak and diffraction peak, respectively, corresponding to crystalline valsartan, indicating that valsartan was present in an amorphous form within the composite nanoparticles (Figure 3). The measured drug content was similar to the theoretical values (Table 1), indicating that valsartan degradation did not occur during the SAS process.


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

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

Scanning electron micrographs of valsartan–HPMC–surfactant composite nanoparticles prepared by using the SAS process.Notes: (A) Valsartan–HPMC; (B) valsartan–HPMC–poloxamer 407; (C) valsartan–HPMC–Ryoto sugar ester L1695; and (D) valsartan–HPMC–TPGS.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

f2-ijn-9-5167: Scanning electron micrographs of valsartan–HPMC–surfactant composite nanoparticles prepared by using the SAS process.Notes: (A) Valsartan–HPMC; (B) valsartan–HPMC–poloxamer 407; (C) valsartan–HPMC–Ryoto sugar ester L1695; and (D) valsartan–HPMC–TPGS.Abbreviations: HPMC, hydroxypropyl methylcellulose; SAS, supercritical antisolvent; TPGS, D-α-Tocopheryl polyethylene glycol 1000 succinate.
Mentions: Ternary compositions, containing polymer in addition to surfactant, may provide effective surface modification and solubilization, resulting in enhanced supersaturation, dissolution rate, and oral absorption of valsartan. However, high amounts of surfactant can induce gastrointestinal tract irritation. Here, the valsartan–HPMC–surfactant composite nanoparticles were fabricated at a 20% drug:70% HPMC:10% surfactant (w/w/w) ratio. As shown in Table 1, the size of valsartan composite nanoparticles increased after the addition of surfactants such as poloxamer 407, Ryoto sugar ester L1695, and TPGS. Valsartan–HPMC–Ryoto sugar ester L1695 particles showed some aggregation and had a specific surface area of 25.2 m2/g (Figure 2). The fusion and aggregation of nanoparticles might be due to the low melting temperature of surfactants, as previously reported.10,18 In fact, the melting points of the used surfactants were below 55°C. However, the mean size of all valsartan–HPMC–surfactant nanoparticles was less than 800 nm. The DSC curves and PXRD patterns of composite nanoparticles did not show the characteristic endothermic melting peak and diffraction peak, respectively, corresponding to crystalline valsartan, indicating that valsartan was present in an amorphous form within the composite nanoparticles (Figure 3). The measured drug content was similar to the theoretical values (Table 1), indicating that valsartan degradation did not occur during the SAS process.

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