Behzad MOKHTARE, Meltem CETİN, Rukiye Sevinc OZAKAR, Hatice BAYRAKCEKEN

6731

Metformin HCl-yüklü Kitosan Mikrokürelerinin Hazırlanması ve In vitro Karakterizasyon Çalışmaları

Bu çalışma, metformin HCl-yüklü kitosan CS mikrokürelerinin MS hazırlanması ve in vitro karakterizasyonu üzerine odaklanmıştır. Taramalı Elektron Mikroskobu SEM görüntüsü küresel mikrokürelerin hazırlandığını göstermiştir. Metformin HCl-yüklü mikrokürelerin partikül büyüklüğü ve enkapsülasyon etkinliği % değerleri sırasıyla 9.21±2.16 µm ve %20.05±6.92 olarak bulunmuştur. Metformin HCl’nin sudaki yüksek çözünürlüğü ve etkin maddenin sulu ortama kaçışı düşük yükleme etkinliği değeri elde edilmesine neden olmuştur. HCl pH 1.2 ve fosfat tamponu PB pH 6.8 ortamlarında yaklaşık %22-36 metformin HCl salımı 1 saat içerisinde ve yaklaşık %89-98 metformin HCl salımı ise 8 gün içerisinde gerçekleşmiştir. Ayrıca, FT-IR ve DSC mikrokürelerin karakterizasyonu için kullanılmıştır. Bu veriler, metformin HCl’nin sürekli salımı için CS mikrokürelerinin potansiyelini göstermektedir.
Anahtar Kelimeler:

DSC, FT-IR, Kitosan, Metformin HCl, Mikroküre

Preparation of Metformin HCl-loaded Chitosan Microspheres and In vitro Characterization Studies

This study focuses on the preparation and in vitro characterisation of metformin HCl-loaded chitosan CS microspheres MS . Scanning Electron Microscopy SEM image shows that the microspheres have spherical shape. The particle size and encapsulation efficiency % value of the metformin HCl-loaded microspheres were found as 9.21±2.16 µm and 20.05±6.92%, respectively. The obtained low drug loading value is due to the high aqueous solubility of metformin HCl, and drug leakage from microspheres to the aqueous medium. In HCl pH 1.2 and phosphate buffer PB pH 6.8 mediums, about 22-36% of metformin HCL was released within 1 hour and about 89-98% of the loaded metformin HCl was released in 8 days. Furthermore, microspheres were characterised using FT-IR and DSC. These data demonstrate a potential for sustained release of metformin HCl by using prepared CS microspheres.
Keywords:

Chitosan, DSC, FT-IR, Metformin HCl, Microsphere,

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  • Channarong, S., Chaicumpa, W., Sinchaipanid, N., Mitrevej, A.: Development and Evaluation of Chitosan-coated Liposomes for Oral DNA Vaccine: The İmprovement of Peyer’s Patch Targeting Using a Polyplex-loaded Liposomes. AAPS Pharm Sci Tech, 12, 192-200 (2011)
  • Sinha, V.R., Singla, A.K., Wadhawan, S., Kaushik, R., Kumria, R., Bansal, K., Dhawan, S.: Chitosan Microspheres as a Potential Carrier for Drugs, Int J Pharm, 274, 1–33 (2004)
  • Emami Riedmaier, A., Fisel, P., Nies, A.T., Schaeffeler, E., Schwab, M.: Metformin and Cancer: From The Old Medicine Cabinet to Pharmacological Pitfalls and Prospects, Trends Pharmacol Sci, 34, 126-135 (2013)
  • Spratt, D.E., Zhang, C., Zumsteg, Z.S., Pei, X., Zhang, Z., Zelefsky, M.J.: Metformin and Prostate Cancer:Reduced Development of Castration-resistant Disease and Prostate Cancer Mortality, Eur Urol, 63, 709-716 (2013)
  • Sweetman S. Martindale: The complete drug reference, Electronic version. London, Pharmaceutical Press, (2007)
  • Corti, G., Cirri, M., Maestrelli, F., Mennini, N., Mura, P.: Sustained-release Matrix Tablets of Metformin Hydrochloride in Combination withTriacetyl- -cyclodextrin, Eur J Pharm Biopharm, 68, 303-309 (2008)
  • Marathe, P.H., Wen, Y., Norton, J., Greene, D.S., Barbhaiya, R.H., Wilding, I.R.: Effect of Altered Gastric Emptying and Gastrointestinal Motility on Metformin Absorption, Br J Clin Pharmacol, 50, 325-332 (2000)
  • Gandhi, K.J., Deshmane, S.V., Biyani, K.R.: Polymers in Pharmaceutical Drug Delivery System: A Review. Int J Pharm Sci Rev Res, 14, 57-66 (2012)
  • Zhang, X., Sun, M., Zheng, A., Cao, D., Bi, Y., Sun, J.: Preparation and Characterization of Insulin-loaded Bioadhesive PLGA Nanoparticles for Oral Administration. Eur J Pharm Sci, 45, 632-638 (2012)
  • Kilicarslan, M., Baykara, T.: The Effect of The Drug/polymer Ratio on The Properties of The Verapamil HCl Loaded Microspheres. Int J Pharm, 252, 99-109 (2003)
  • Fattal, E., Quaglia, F., Gupta, P., Brazeau, G., “Biodegradable microparticles for the development of less-painful and less irritating parenterals”, Gupta, P., Brazeau, G. (Eds.), Injectable Drug Development:Techniques to Reduce Pain and Irritation, Colorado, Interpharm Press, (1999), 355-378.
  • Tuncay, M., Calis, S., Kas, H.S., Ercan, M.T., Peksoy, I., Hincal, A.A.: Diclofenac Sodium Incorporated PLGA (50:50) Microspheres: Formulation Considerations and In vitro/In vivo Evaluation, Int J Pharm, 195, 179-188 (2000)
  • Song, X., Zhao, Y., Wu, W., Bi, Y., Cai, Z., Chen, Q., Li, Y, Hou, S.: PLGA Nanoparticles Simultaneously Loaded with Vincristine Sulphate and Verapamil Hydrochloride: Systematic Study of Particle Size and Drug Entrapment Efficiency, Int J Pharm, 350, 320-329, (2008)
  • Sutar, P.S., Sutar, K.P., Sambrekar, A.S., Patil, V.S., Kudalagi, C.R.: Formulation and Evaluation of Metformin Hydrochloride Loaded Chitosan Microspheres, JPSI, 1, 12-16 (2012)
  • Wang, L.C., Di, L.Q., Liu, R., Wu, H.: Characterizations and Microsphere Formulation of Polysaccharide from the Marine Clam (Mactra Veneriformis). Carbohydr Polym, 92, 106- 113 (2013).
  • Madsen, K.D., Sander, C., Baldursdottir, S., Pedersen, A.M., Jacobsen, J.: Development of an Ex Vivo Retention Model Simulating Bioadhesion in the Oral Cavity Using Human Saliva and Physiologically Relevant Irrigation Media, Int J Pharm, 448, 373–381 (2013)
  • Gonçalves, V.L., Laranjeira M.C.M., Fávere V.T.: Effect of Crosslinking Agents on Chitosan Microspheres in Controlled Release of Diclofenac Sodium, Polímeros, 15, 6-12 (2005)
  • Nayak, U.Y., Gopal, S., Mutalik, S., Ranjith, A.K., Reddy, M.S., Gupta, P., Udupa, N.: Glutaraldehyde Cross-Linked Chitosan Microspheres for Controlled Delivery of Zidovudine, J Microencapsul, 26, 214–222 (2009)
  • Cevher, E., Orhan, Z., Mülazimoğlu, L., Sensoy, D., Alper, M., Yildiz, A., Ozsoy, Y.: Characterization of Biodegradable Chitosan Microspheres Containing Vancomycin and Treatment of Experimental Osteomyelitis Caused by Methicillin-Resistant Staphylococcus Aureus with Prepared Microspheres, Int J Pharm, 317, 127-135 (2006)
  • Gazori, T., Khoshayand, M.R., Azizi, E., Yazdizade, P., Nomani, A., Haririan, I.: Evaluation of Alginate/Chitosan Nanoparticles as Antisense Delivery Vector: Formulation, Optimization and In Vitro Characterization, Carbohydrate Polymers, 77, 599-606 (2009)
  • Tripathi, S., Mehrotra, G.K., Dutta, P.K.: Physicochemical and Bioactivity of Cross-Linked Chitosan–PVA Film for Food Packaging Applications. Int J Biol Macromol, 45, 372-376 (2009)
  • Yang, J.M., Chiu, H.C.: Preparation and Characterization of Polyvinyl Alcohol/Chitosan Blended Membrane for Alkaline Direct Methanol Fuel Cells, J Membrane Sci, 419-420, 65- 71 (2012)
  • Block, L.C., Schmeling, L.O., Couto, A.G., Silva, M.A.S., Tagliari, M.P., Bresolin, T.M.B., Mourão, S.C.: Effect of Binders On 500 mg Metformin Hydrochloride Tablets Produced by Wet Granulation, Rev Ciênc Farm Básica Apl, 30, 145-152 (2009)
  • Ashok Kumar, A., Balakrishna,T., Rajiv, J., Murthy, T.E.G.K , Anıl Kumar, Sudheer, B.: Formulation and Evaluation of Mucoadhesive Microcapsules of Metformin HCl with Gum Karaya. Int J Pharm Pharm Sci, 3, 150-155 (2011)
  • Pandit, V., Pai, R.S., Yadav, V., Devi, K., Surekha, B.B., Inamdar, M.N., Suresh S.: Pharmacokinetic and Pharmacodynamic Evaluation of Floating Microspheres of Metformin Hydrochloride, Drug Dev Ind Pharm, 39, 117-127 (2013)
  • Banerjee, P., Deb, J., Roy, A., Ghosh, A., Chakraborty, P., Fabrication and Development of Pectin Microsphere of Metformin Hydrochloride. ISRN Pharmaceutics, 1-7 (2012) doi:10.5402/2012/230621
  • Gunasekaran, S., Natarajan, R.K., Renganayaki, V., Natarajan, S.: Vibrational Spectra and Thermodynamic Analysis of Metformin. IJPAP, 44, 495-500 (2006)
  • Mourya, V.K., Inamdara, N.N., Tiwari, A., Carboxymethyl Chitosan and Its Applications. Adv Mat Lett, 1, 11-33 (2010)
  • Gonil, P., Sajomsang, W., Ruktanonchai, U.R., Pimpha, N., Sramala, I., Nuchuchua, O., Saesoo, S., Chaleawlert-umpon, S., Puttipipatkhachorn, S.: Novel Quaternized Chitosan Containing -Cyclodextrin Moiety: Synthesis, Characterization and Antimicrobial Activity, Carbohydrate Polymers, 83, 905-913 (2011)
  • Salehizadeh, H., Hekmatian, E., Sadeghi, M., Kennedy, K.: Synthesis and Characterization of Core-shell Fe3O4-gold-chitosan Nanostructure, J Nanobiotechnol, 10, 3 (2012) doi:10.1186/1477-3155-10-3
Hacettepe Üniversitesi Eczacılık Fakültesi Dergisi-Cover
  • Yayın Aralığı: Yılda 4 Sayı
  • Başlangıç: 1981
  • Yayıncı: Hacettepe Üniversitesi Eczacılık Fakültesi Dekanlığı
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