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Formulation and optimization of alginate-methotrexate microspheres produced by emulsification technique

S, Hashem Monta
Shohre Alipour
Saba afifi,
Department of Pharmaceutics, Faculty of Pharmacy, Shiraz University of Medical Sciences, P.O. Box 71345-1583, Shiraz, Iran
Recently, much research has been focused on degradable polymer microspheres for drug
delivery. Administration of chemotherapeutic agents such as methotrexate via such
systems is advantageous. Because microspheres can be ingested or injected; they can be
tailored for desired release profiles and in some cases even provide organ-targeted
release. So lower dosed and less frequent injections as a result of localized therapy and
controlled release make a microspheres drug delivery system a good candidate for cancer
therapy. Among the wide spectrum of polymers, alginate is so popular because of its
safety, biocompatibility, biodegradability and non-immunogenicity.
Experimental Method:
In this study we have used emulsification- internal gelation method. The alginate
microspheres were produced by cross-linking alginate globules dispersed in a continuous
organic phase using various concentrations of calcium chloride solution. Different
parameters in formulation have been studied such as alginate type (low viscosity &
medium viscosity) and concentration (1-5%), calcium concentration (0.25-3.5%),
surfactant concentration (1-3%) and curing time. Microspheres’ size was determined by
laser diffraction particle size analyzer. The size of microspheres and amount of drug
loaded was the comparison factor for different formulations. The encapsulation
efficiency was determined by HPLC method.
Results and Discussion:
The formulation containing a mixture of 0.5%HPMC and 4.5% alginate cured in 0.75%
calcium chloride for 20 minutes was chosen as the best formula regarding the particle
size and the loading efficiency. The resulting microspheres had a volume mean diameter
of 6 µm and loading efficiency of about 20%.
Key words: methotrexate, alginates, Microspheres
[1] Anamika Roy, J. Bajpai, A.K. Bajpai ,Carbohydrate Polymers, In Press.
[2] Chaoyang Wang, Hongxia Liu, Quanxing Gao, Xinxing Liu, Zhen Tong, Carbohydrate Polymers, Volume 71, Issue 3, 8 February 2008, Pages 476-480.
NanoSpain2009 09-12 March, 2009 Zaragoza-Spain [3] Susana Martins, Bruno Sarmento, Eliana B. Souto, Domingos C. Ferreira , Carbohydrate Polymers, Volume 69, Issue 4, 2 July 2007, Pages 725-731. [4] R. Rastogi, Y. Sultana, M. Aqil, A. Ali, S. Kumar, K. Chuttani, A.K. Mishra, International Journal of Pharmaceutics, Volume 334, Issues 1-2, 4 April 2007, Pages 71-77. Biomaterials, Volume 28, Issue 20, July 2007, Pages 3140-3152 [6] A. Lebugle, A. Rodrigues, P. Bonnevialle, J. J. Voigt, P. Canal, F. Rodriguez, Biomaterials, NanoSpain2009 09-12 March, 2009 Zaragoza-Spain


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