Sustained release optimized formulation of anastrozole-loaded chitosan microspheres

In vitro and in vivo evaluation

Gopal V. Shavi, Usha Y. Nayak, M. Sreenivasa Reddy, A. Karthik, Praful B. Deshpande, A. Ranjith Kumar, N. Udupa

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

The purpose of this study was to develop sustained release formulation of anastrozole-loaded chitosan microspheres for treatment of breast cancer. Chitosan microspheres cross-linked with two different cross-linking agents viz, tripolyphosphate (TPP) and glutaraldehyde (GA) were prepared using single emulsion (w/o) method. A reverse phase HPLC method was developed and used for quantification of drug in microspheres and rat plasma. Influence of cross-linking agents on the properties of chitosan microspheres was extensively investigated. Formulations were characterized for encapsulation efficiency (EE), compatibility of drug with excipients, particle size, surface morphology, swelling capacity, erosion and drug release profile in phosphate buffer pH 7.4. EE varied from 30.4 ± 1.2 to 69.2 ± 3.2% and mean particle size distribution ranged from 72.5 ± 0.5 to 157.9 ± 1.5 lm. SEM analysis revealed smooth and spherical nature of microspheres. TPP microspheres exhibited higher swelling capacity, percentage erosion and drug release compared to GA microspheres. Release of anastrozole (ANS) was rapid up to 4 h followed by slow release status. FTIR analysis revealed no chemical interaction between drug and polymer. DSC analysis indicated ANS trapped in the microspheres existed in amorphous form in polymer matrix. The highest correlation coefficients (R2) were obtained for Higuchi model, suggesting a diffusion controlled mechanism. There was significant difference in the pharmacokinetic parameters (AUC0-∞ Kel and t1/2) when ANS was formulated in the form of microspheres compared to pure drug. This may be attributed to slow release rate of ANS from chitosan microspheres and was detectable in rat plasma up to 48 h which correlates well with the in vitro release data.

Original languageEnglish
Pages (from-to)865-878
Number of pages14
JournalJournal of Materials Science: Materials in Medicine
Volume22
Issue number4
DOIs
Publication statusPublished - 04-2011

Fingerprint

Chitosan
Microspheres
Pharmaceutical Preparations
Glutaral
Encapsulation
Particle Size
Swelling
Rats
Erosion
Polymers
anastrozole
In Vitro Techniques
Drug interactions
Plasmas
Pharmacokinetics
Excipients
Fourier Transform Infrared Spectroscopy
Emulsions
Polymer matrix
Drug Interactions

All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Biophysics
  • Biomaterials
  • Biomedical Engineering

Cite this

@article{ad9995cac90f41eb8dbb0853447178b1,
title = "Sustained release optimized formulation of anastrozole-loaded chitosan microspheres: In vitro and in vivo evaluation",
abstract = "The purpose of this study was to develop sustained release formulation of anastrozole-loaded chitosan microspheres for treatment of breast cancer. Chitosan microspheres cross-linked with two different cross-linking agents viz, tripolyphosphate (TPP) and glutaraldehyde (GA) were prepared using single emulsion (w/o) method. A reverse phase HPLC method was developed and used for quantification of drug in microspheres and rat plasma. Influence of cross-linking agents on the properties of chitosan microspheres was extensively investigated. Formulations were characterized for encapsulation efficiency (EE), compatibility of drug with excipients, particle size, surface morphology, swelling capacity, erosion and drug release profile in phosphate buffer pH 7.4. EE varied from 30.4 ± 1.2 to 69.2 ± 3.2{\%} and mean particle size distribution ranged from 72.5 ± 0.5 to 157.9 ± 1.5 lm. SEM analysis revealed smooth and spherical nature of microspheres. TPP microspheres exhibited higher swelling capacity, percentage erosion and drug release compared to GA microspheres. Release of anastrozole (ANS) was rapid up to 4 h followed by slow release status. FTIR analysis revealed no chemical interaction between drug and polymer. DSC analysis indicated ANS trapped in the microspheres existed in amorphous form in polymer matrix. The highest correlation coefficients (R2) were obtained for Higuchi model, suggesting a diffusion controlled mechanism. There was significant difference in the pharmacokinetic parameters (AUC0-∞ Kel and t1/2) when ANS was formulated in the form of microspheres compared to pure drug. This may be attributed to slow release rate of ANS from chitosan microspheres and was detectable in rat plasma up to 48 h which correlates well with the in vitro release data.",
author = "Shavi, {Gopal V.} and Nayak, {Usha Y.} and {Sreenivasa Reddy}, M. and A. Karthik and Deshpande, {Praful B.} and {Ranjith Kumar}, A. and N. Udupa",
year = "2011",
month = "4",
doi = "10.1007/s10856-011-4274-y",
language = "English",
volume = "22",
pages = "865--878",
journal = "Journal of Materials Science: Materials in Medicine",
issn = "0957-4530",
publisher = "Springer Netherlands",
number = "4",

}

Sustained release optimized formulation of anastrozole-loaded chitosan microspheres : In vitro and in vivo evaluation. / Shavi, Gopal V.; Nayak, Usha Y.; Sreenivasa Reddy, M.; Karthik, A.; Deshpande, Praful B.; Ranjith Kumar, A.; Udupa, N.

In: Journal of Materials Science: Materials in Medicine, Vol. 22, No. 4, 04.2011, p. 865-878.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Sustained release optimized formulation of anastrozole-loaded chitosan microspheres

T2 - In vitro and in vivo evaluation

AU - Shavi, Gopal V.

AU - Nayak, Usha Y.

AU - Sreenivasa Reddy, M.

AU - Karthik, A.

AU - Deshpande, Praful B.

AU - Ranjith Kumar, A.

AU - Udupa, N.

PY - 2011/4

Y1 - 2011/4

N2 - The purpose of this study was to develop sustained release formulation of anastrozole-loaded chitosan microspheres for treatment of breast cancer. Chitosan microspheres cross-linked with two different cross-linking agents viz, tripolyphosphate (TPP) and glutaraldehyde (GA) were prepared using single emulsion (w/o) method. A reverse phase HPLC method was developed and used for quantification of drug in microspheres and rat plasma. Influence of cross-linking agents on the properties of chitosan microspheres was extensively investigated. Formulations were characterized for encapsulation efficiency (EE), compatibility of drug with excipients, particle size, surface morphology, swelling capacity, erosion and drug release profile in phosphate buffer pH 7.4. EE varied from 30.4 ± 1.2 to 69.2 ± 3.2% and mean particle size distribution ranged from 72.5 ± 0.5 to 157.9 ± 1.5 lm. SEM analysis revealed smooth and spherical nature of microspheres. TPP microspheres exhibited higher swelling capacity, percentage erosion and drug release compared to GA microspheres. Release of anastrozole (ANS) was rapid up to 4 h followed by slow release status. FTIR analysis revealed no chemical interaction between drug and polymer. DSC analysis indicated ANS trapped in the microspheres existed in amorphous form in polymer matrix. The highest correlation coefficients (R2) were obtained for Higuchi model, suggesting a diffusion controlled mechanism. There was significant difference in the pharmacokinetic parameters (AUC0-∞ Kel and t1/2) when ANS was formulated in the form of microspheres compared to pure drug. This may be attributed to slow release rate of ANS from chitosan microspheres and was detectable in rat plasma up to 48 h which correlates well with the in vitro release data.

AB - The purpose of this study was to develop sustained release formulation of anastrozole-loaded chitosan microspheres for treatment of breast cancer. Chitosan microspheres cross-linked with two different cross-linking agents viz, tripolyphosphate (TPP) and glutaraldehyde (GA) were prepared using single emulsion (w/o) method. A reverse phase HPLC method was developed and used for quantification of drug in microspheres and rat plasma. Influence of cross-linking agents on the properties of chitosan microspheres was extensively investigated. Formulations were characterized for encapsulation efficiency (EE), compatibility of drug with excipients, particle size, surface morphology, swelling capacity, erosion and drug release profile in phosphate buffer pH 7.4. EE varied from 30.4 ± 1.2 to 69.2 ± 3.2% and mean particle size distribution ranged from 72.5 ± 0.5 to 157.9 ± 1.5 lm. SEM analysis revealed smooth and spherical nature of microspheres. TPP microspheres exhibited higher swelling capacity, percentage erosion and drug release compared to GA microspheres. Release of anastrozole (ANS) was rapid up to 4 h followed by slow release status. FTIR analysis revealed no chemical interaction between drug and polymer. DSC analysis indicated ANS trapped in the microspheres existed in amorphous form in polymer matrix. The highest correlation coefficients (R2) were obtained for Higuchi model, suggesting a diffusion controlled mechanism. There was significant difference in the pharmacokinetic parameters (AUC0-∞ Kel and t1/2) when ANS was formulated in the form of microspheres compared to pure drug. This may be attributed to slow release rate of ANS from chitosan microspheres and was detectable in rat plasma up to 48 h which correlates well with the in vitro release data.

UR - http://www.scopus.com/inward/record.url?scp=80051664113&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80051664113&partnerID=8YFLogxK

U2 - 10.1007/s10856-011-4274-y

DO - 10.1007/s10856-011-4274-y

M3 - Article

VL - 22

SP - 865

EP - 878

JO - Journal of Materials Science: Materials in Medicine

JF - Journal of Materials Science: Materials in Medicine

SN - 0957-4530

IS - 4

ER -