Effect of particle size and surfactant on the solubility, permeability and dissolution characteristics of deferasirox

Yagmur Akdag; Levent Öner; Selma Şahin

Makale detayları

Effect of particle size and surfactant on the solubility, permeability and dissolution characteristics of deferasirox

Yazarlar:

Yagmur Akdag | Levent Öner | Selma Şahin

Yayıncı:

Marmara University

Ana Başlıklar:

Pharmaceutical Chemistry | Pharmaceutical Delivery Technologies

Dergi:

Journal of Research in Pharmacy Vol.23 Issue 5, pp.851-859

Belge Tipi:

Makale

Yayın Tarihi:

6/2025

Belge Dili:

İngilizce

Document ID (Org No.):

2001347974

pISSN:

2630-6344

Anahtar kelimeler:

Özet:

 Deferasirox is an oral iron chelator used for the treatment of chronic iron overload in blood transfusions. Deferasirox is a BCS Class II drug with low solubility and high permeability. In the formulation development stage for BCS Class II compounds, one of the main approaches is solubility enhancement to achieve better dissolution profiles, increased bioavailability and in some cases, dose reduction. The aim of the study was to investigate the effect of particle size and surfactant on the solubility, permeability and dissolution characteristics of deferasirox. Ball milling method was used to reduce the particle size of deferasirox. Pluronic F127 or sodium lauril sulfate SLS were selected as surfactants at different concentrations. The maximum increase in the solubility was obtained with 10 SLS at pH 1.2 from 0.9 µgmL to 333.7 µgmL, and with 5 Pluronic F127 at pH 6.8 from 46.8 µgmL to 334.2 µgmL. Dissolution studies revealed that time to dissolve 85 of deferasirox was decreased as a function of ball milling time and particle size. Permeability studies showed that, in 100 µM concentration, deferasirox permeability was significantly enhanced by all concentrations of SLS p0.05. With an increase in Pluronic F127 concentration, permeability of deferasirox was not altered p0.05. All these results clearly demonstrated that surfactant addition to the formulations was effective for solubility enhancement of deferasirox, and surfactant type in optimized concentrations was very crucial. Particle size reduction can be used as a promising approach to improve dissolution, and hence bioavailability of deferasirox.

 Deferasirox is an oral iron chelator used for the treatment of chronic iron overload in blood transfusions. Deferasirox is a BCS Class II drug with low solubility and high permeability. In the formulation development stage for BCS Class II compounds, one of the main approaches is solubility enhancement to achieve better dissolution profiles, increased bioavailability and in some cases, dose reduction. The aim of the study was to investigate the effect of particle size and surfactant on the solubility, permeability and dissolution characteristics of deferasirox. Ball milling method was used to reduce the particle size of deferasirox. Pluronic F127 or sodium lauril sulfate SLS were selected as surfactants at different concentrations. The maximum increase in the solubility was obtained with 10 SLS at pH 1.2 from 0.9 µgmL to 333.7 µgmL, and with 5 Pluronic F127 at pH 6.8 from 46.8 µgmL to 334.2 µgmL. Dissolution studies revealed that time to dissolve 85 of deferasirox was decreased as a function of ball milling time and particle size. Permeability studies showed that, in 100 µM concentration, deferasirox permeability was significantly enhanced by all concentrations of SLS p0.05. With an increase in Pluronic F127 concentration, permeability of deferasirox was not altered p0.05. All these results clearly demonstrated that surfactant addition to the formulations was effective for solubility enhancement of deferasirox, and surfactant type in optimized concentrations was very crucial. Particle size reduction can be used as a promising approach to improve dissolution, and hence bioavailability of deferasirox.

 Deferasirox is an oral iron chelator used for the treatment of chronic iron overload in blood transfusions. Deferasirox is a BCS Class II drug with low solubility and high permeability. In the formulation development stage for BCS Class II compounds, one of the main approaches is solubility enhancement to achieve better dissolution profiles, increased bioavailability and in some cases, dose reduction. The aim of the study was to investigate the effect of particle size and surfactant on the solubility, permeability and dissolution characteristics of deferasirox. Ball milling method was used to reduce the particle size of deferasirox. Pluronic F127 or sodium lauril sulfate SLS were selected as surfactants at different concentrations. The maximum increase in the solubility was obtained with 10 SLS at pH 1.2 from 0.9 µgmL to 333.7 µgmL, and with 5 Pluronic F127 at pH 6.8 from 46.8 µgmL to 334.2 µgmL. Dissolution studies revealed that time to dissolve 85 of deferasirox was decreased as a function of ball milling time and particle size. Permeability studies showed that, in 100 µM concentration, deferasirox permeability was significantly enhanced by all concentrations of SLS p0.05. With an increase in Pluronic F127 concentration, permeability of deferasirox was not altered p0.05. All these results clearly demonstrated that surfactant addition to the formulations was effective for solubility enhancement of deferasirox, and surfactant type in optimized concentrations was very crucial. Particle size reduction can be used as a promising approach to improve dissolution, and hence bioavailability of deferasirox.

 Deferasirox is an oral iron chelator used for the treatment of chronic iron overload in blood transfusions. Deferasirox is a BCS Class II drug with low solubility and high permeability. In the formulation development stage for BCS Class II compounds, one of the main approaches is solubility enhancement to achieve better dissolution profiles, increased bioavailability and in some cases, dose reduction. The aim of the study was to investigate the effect of particle size and surfactant on the solubility, permeability and dissolution characteristics of deferasirox. Ball milling method was used to reduce the particle size of deferasirox. Pluronic F127 or sodium lauril sulfate SLS were selected as surfactants at different concentrations. The maximum increase in the solubility was obtained with 10 SLS at pH 1.2 from 0.9 µgmL to 333.7 µgmL, and with 5 Pluronic F127 at pH 6.8 from 46.8 µgmL to 334.2 µgmL. Dissolution studies revealed that time to dissolve 85 of deferasirox was decreased as a function of ball milling time and particle size. Permeability studies showed that, in 100 µM concentration, deferasirox permeability was significantly enhanced by all concentrations of SLS p0.05. With an increase in Pluronic F127 concentration, permeability of deferasirox was not altered p0.05. All these results clearly demonstrated that surfactant addition to the formulations was effective for solubility enhancement of deferasirox, and surfactant type in optimized concentrations was very crucial. Particle size reduction can be used as a promising approach to improve dissolution, and hence bioavailability of deferasirox.

Makale detayları

Effect of particle size and surfactant on the solubility, permeability and dissolution characteristics of deferasirox

Yazarlar:

Yagmur Akdag | Levent Öner | Selma Şahin

Yayıncı:

Marmara University

Ana Başlıklar:

Pharmaceutical Chemistry | Pharmaceutical Delivery Technologies

Dergi:

Journal of Research in Pharmacy Vol.23 Issue 5, pp.851-859

Belge Tipi:

Makale

Yayın Tarihi:

6/2025

Belge Dili:

İngilizce

Document ID (Org No.):

2001347974

pISSN:

2630-6344

Deferasirox

dissolution

particle size distribution

permeability

solubility

surfactant

Sayı

Makale detayları

Effect of particle size and surfactant on the solubility, permeability and dissolution characteristics of deferasirox

Yazarlar: Yagmur Akdag | Levent Öner | Selma Şahin

Yayıncı: Marmara University

Ana Başlıklar: Pharmaceutical Chemistry | Pharmaceutical Delivery Technologies

Dergi: Journal of Research in Pharmacy Vol.23 Issue 5, pp.851-859

Belge Tipi: Makale

Yayın Tarihi: 6/2025

Belge Dili: İngilizce

Document ID (Org No.): 2001347974

pISSN: 2630-6344

Deferasirox

dissolution

particle size distribution

permeability

solubility

surfactant

Sayı

Yazarlar:

Yagmur Akdag | Levent Öner | Selma Şahin

Yayıncı:

Marmara University

Ana Başlıklar:

Pharmaceutical Chemistry | Pharmaceutical Delivery Technologies

Dergi:

Journal of Research in Pharmacy Vol.23 Issue 5, pp.851-859

Belge Tipi:

Makale

Yayın Tarihi:

6/2025

Belge Dili:

İngilizce

Document ID (Org No.):

2001347974

pISSN:

2630-6344