Metoprolol Tartrate-Ethylcellulose Tabletted Microparticles: Development of a Validated Invitro In-vivo Correlation
This study describes the methodology for the development of a validated in-vitro in-vivo correlation (IVIVC) for metoprolol tartrate modified release dosage forms with distinctive release rate characteristics. Modified release dosage forms were formulated by microencapsulation of metoprolol tartrate into different amounts of ethylcellulose by non-solvent addition technique. Then in-vitro and in-vivo studies were conducted to develop and validate level A IVIVC for metoprolol tartrate. The values of regression co-efficient (R2-values) for IVIVC of T2 and T3 formulations were not significantly (p<0.05) different from 1 while the values of R2 for IVIVC of T1 and Mepressor® were significantly (p<0.05) different from 1. Internal prediction errors of IVIVC, calculated from observed Area under Curve (AUC) and predicted AUC, were less than 10%. This study successfully presents a valid level A IVIVC for metoprolol tartrate modified dosage forms.
[1] H. Rettig, J. Mysicka. (2008, February). IVIVC: Methods and
Applications in Modified-Release Product Development. Dissol.
Technol. (Online). 15. pp. 6-9. Available:
www.dissolutiontech.com/DTresour/.../DT200802_A01.pdf
[2] U.S. Department of Health and Human Services. (1997, September).
Guidance for industrial. Extended release oral dosage forms:
Development, evaluation and application of In Vitro/In Vivo
correlations. Food and Drug Administration, Center for Drug Evaluation
and Research (CDER). Rockville, MD. Available:
www.fda.gov/.../Drugs/GuidanceComplianceRegulatoryInformation/Gui
dances/UCM070239.pdf
[3] G. Murtaza, M. Ahmad, N. Akhtar. (2009, August). Biowaiver study of
oral tabletted ethylcellulose microcapsules of a BCS class I drug. Bull.
Chem. Soc. Ethiop. (Online). 23 (2). pp. 1-16. Available:
http://ajol.info/index.php/bcse/article/view/44959/0
[4] R. V. Nellore, G. S. Rekhi, A. S. Hussain, G. L. Tillman, L. L.
Augsburger. (1998, January). Development of metoprolol tartrate
extended-release matrix tablet formulations for regulatory policy
consideration. J. Control. Release (Online). 50 (2). pp. 247-256.
Available: http://www.ncbi.nlm.nih.gov/pubmed/9685891
[5] G. Murtaza, M. Ahamd, N. Akhtar, F. Rasool. (2009, July). A
comparative study of various microencapsulation techniques: Effect of
polymer viscosity on microcapsule characteristics. Pak. J. Pharm. Sci.
(Online). 22 (3). pp. 291-300. Available: www.pjps.pk/CD-PJPS-22-3-
09/Paper-10.pdf
[6] N. D. Eddington. In Vitro In Vivo Correlation with Metoprolol Extended
Release Tablets Using Two Different Releasing Formulations: An
Internal Validation Evaluation. Published at http://www.locumusa.com.
Int. J. Generic Drugs (Online). pp. 417-429. Available:
http://www.locumusa.com
[7] U.S. Department of Health and Human Services. (1995, November).
Guidance for industry: Modified release solid oral dosage forms scale-up
and postapproval changes: chemistry, manufacturing, and controls, in
vitro dissolution testing, and in vivo bioequivalence documentation.
Center for drug Evaluation and Research, Food and Drug
Administration. Rockville, MD.
Available:www.fda.gov/.../Drugs/GuidanceComplianceRegulatoryInfor
mation/Guidances/UCM070636.pdf
[8] N. D. Eddington, P. Marroum, R. Uppoor, A. Hussain, L. Augsburger.
(1998, March). Development of an In Vitro-In Vivo Correlation for a
hydrophilic Metoprolol tartaret extended release tablet formulation.
Pharm. Res. (Online). 15(3). pp. 466-473. Available:
www.locumusa.com/pdf/members/ivivc-03.pdf
[9] F. Rasool, M. Ahmad, G. Murtaza, S. A. Khan, M. N. Aamir. (2010, 21
January). Hydrophilic plastic polymeric tabletted microparticles loaded
with metoprolol tartrate: Formulation and in-vitro evaluation. Submitted
for publication in Latin Am. J. Pham. (Online). Available:
http://www.latamjpharm.org/
[10] S. Klein, J. B. Dressman. (2007, February). Comparison of drug release
from metoprolol modified release dosage forms in single buffer versus a
pH-gradient dissolution test. Dissol. Technol. (Online). 13: 6-12.
Available: www.dissolutiontech.com/DTresour /.../DT200602_A01.pdf
[11] M. Aqil, A. Ali, A. Ahad, Y. Sultana, A. K. Najmi, N. Saha. (2007,
December). A validated HPLC method for estimation of metoprolol in
human plasma. Acta Chromatogr. (Online). 19. pp. 130-140.
Available:livewww.us.edu.pl/uniwersytet/jednostki/wydzia
ly/chemia/.../11_AC19.pdf
[1] H. Rettig, J. Mysicka. (2008, February). IVIVC: Methods and
Applications in Modified-Release Product Development. Dissol.
Technol. (Online). 15. pp. 6-9. Available:
www.dissolutiontech.com/DTresour/.../DT200802_A01.pdf
[2] U.S. Department of Health and Human Services. (1997, September).
Guidance for industrial. Extended release oral dosage forms:
Development, evaluation and application of In Vitro/In Vivo
correlations. Food and Drug Administration, Center for Drug Evaluation
and Research (CDER). Rockville, MD. Available:
www.fda.gov/.../Drugs/GuidanceComplianceRegulatoryInformation/Gui
dances/UCM070239.pdf
[3] G. Murtaza, M. Ahmad, N. Akhtar. (2009, August). Biowaiver study of
oral tabletted ethylcellulose microcapsules of a BCS class I drug. Bull.
Chem. Soc. Ethiop. (Online). 23 (2). pp. 1-16. Available:
http://ajol.info/index.php/bcse/article/view/44959/0
[4] R. V. Nellore, G. S. Rekhi, A. S. Hussain, G. L. Tillman, L. L.
Augsburger. (1998, January). Development of metoprolol tartrate
extended-release matrix tablet formulations for regulatory policy
consideration. J. Control. Release (Online). 50 (2). pp. 247-256.
Available: http://www.ncbi.nlm.nih.gov/pubmed/9685891
[5] G. Murtaza, M. Ahamd, N. Akhtar, F. Rasool. (2009, July). A
comparative study of various microencapsulation techniques: Effect of
polymer viscosity on microcapsule characteristics. Pak. J. Pharm. Sci.
(Online). 22 (3). pp. 291-300. Available: www.pjps.pk/CD-PJPS-22-3-
09/Paper-10.pdf
[6] N. D. Eddington. In Vitro In Vivo Correlation with Metoprolol Extended
Release Tablets Using Two Different Releasing Formulations: An
Internal Validation Evaluation. Published at http://www.locumusa.com.
Int. J. Generic Drugs (Online). pp. 417-429. Available:
http://www.locumusa.com
[7] U.S. Department of Health and Human Services. (1995, November).
Guidance for industry: Modified release solid oral dosage forms scale-up
and postapproval changes: chemistry, manufacturing, and controls, in
vitro dissolution testing, and in vivo bioequivalence documentation.
Center for drug Evaluation and Research, Food and Drug
Administration. Rockville, MD.
Available:www.fda.gov/.../Drugs/GuidanceComplianceRegulatoryInfor
mation/Guidances/UCM070636.pdf
[8] N. D. Eddington, P. Marroum, R. Uppoor, A. Hussain, L. Augsburger.
(1998, March). Development of an In Vitro-In Vivo Correlation for a
hydrophilic Metoprolol tartaret extended release tablet formulation.
Pharm. Res. (Online). 15(3). pp. 466-473. Available:
www.locumusa.com/pdf/members/ivivc-03.pdf
[9] F. Rasool, M. Ahmad, G. Murtaza, S. A. Khan, M. N. Aamir. (2010, 21
January). Hydrophilic plastic polymeric tabletted microparticles loaded
with metoprolol tartrate: Formulation and in-vitro evaluation. Submitted
for publication in Latin Am. J. Pham. (Online). Available:
http://www.latamjpharm.org/
[10] S. Klein, J. B. Dressman. (2007, February). Comparison of drug release
from metoprolol modified release dosage forms in single buffer versus a
pH-gradient dissolution test. Dissol. Technol. (Online). 13: 6-12.
Available: www.dissolutiontech.com/DTresour /.../DT200602_A01.pdf
[11] M. Aqil, A. Ali, A. Ahad, Y. Sultana, A. K. Najmi, N. Saha. (2007,
December). A validated HPLC method for estimation of metoprolol in
human plasma. Acta Chromatogr. (Online). 19. pp. 130-140.
Available:livewww.us.edu.pl/uniwersytet/jednostki/wydzia
ly/chemia/.../11_AC19.pdf
@article{"International Journal of Medical, Medicine and Health Sciences:59992", author = "Fatima Rasool and Mahmood Ahmad and Ghulam Murtaza and Haji M. S. Khan and Shujaat A. Khan and Sonia Khiljee and Muhammad Qamar-Uz-Zaman", title = "Metoprolol Tartrate-Ethylcellulose Tabletted Microparticles: Development of a Validated Invitro In-vivo Correlation", abstract = "This study describes the methodology for the development of a validated in-vitro in-vivo correlation (IVIVC) for metoprolol tartrate modified release dosage forms with distinctive release rate characteristics. Modified release dosage forms were formulated by microencapsulation of metoprolol tartrate into different amounts of ethylcellulose by non-solvent addition technique. Then in-vitro and in-vivo studies were conducted to develop and validate level A IVIVC for metoprolol tartrate. The values of regression co-efficient (R2-values) for IVIVC of T2 and T3 formulations were not significantly (p", keywords = "Metoprolol tartrate, Dissolution, Bioavailability, Validated in-vitro in-vivo correlation.", volume = "4", number = "3", pages = "74-4", }
