Cenk YILDIZ, Gülen Melike DEMİRBOLAT, Mustafa ERGÜL

Metoprolol tartaratın kontrollü salımı için kitozan mikropartiküllerinin geliştirilmesi

Yüksek kan basıncı olarak tanımlanan hipertansiyon kardiyovasküler yetersizliklere ve erken ölümlere neden olan yaygın medical bir durumdur. Kan basıncının etkili bir şekilde kontrol altına alınması hipertansiyonun önlenmesinde ana hedef olarak kabul edilmektedir. Konvansiyonel dozaj formlarının (hemen salım yapan tabletler, kapsüller gibi) bazı kısıtlamalara sahip olmaları nedeniyle modifiye ilaç salım sistemlerinin tasarımı büyük ilgi uyandırmıştır. Modifiye salım; ilacın verilişinden belli bir süre sonrasında veya uzatılmış bir zaman diliminde dozaj formundan ilacın çıkışı olarak tanımlanmaktadır. Bu çalışmada, modifiye salım elde etmek için metoprolol tartarat yüklü kitozan mikropartiküllerinin üretilmesi amaçlanmıştır. Kitozan mikropartikülleri; çapraz bağlı ajan olarak kullanılan tripolifosfat ile iyonik jelasyon yöntemine göre üretilmiştir. Hazırlanan formülasyonlar karakterize edilmiş ve etkin madde içermeyen optimum mikropartiküllere metoprolol tartarat yüklenmiştir. İlaç yükleme kapasitesi, yükleme etkinliği, hücre canlılığı ve in vitro ilaç salımı incelenmiştir. En iyi formülasyon küresel yapılı %81 verim ile 75.373±7.384μm partikül büyüklüğünde elde edilmiştir. Micropartiküllere 16 mg metoprolol tartarat yüklenebilmiş ve ilaç salımı 48 saat boyunca sürdürülmüştür.

Development of chitosan microparticles for controlled release of metoprolol tartarate

Hypertension, defined as high blood pressure, is a common medical condition leading to cardiovascular disability andpremature deaths. Blood pressure control in an efficient way are assumed to the main targets to prevent hypertension.Since conventional dosage forms (e.g. immediate release tablets, capsules, etc.) show some limitation, greater attentionis being paid on designing the modified drug release systems. Modified release is defined as drug releasing from dosageform some time after the administration or in prolonged period of time. In this study, we aimed to design metoprololtartarate loaded chitosan microparticles to obtained modified drug release. Chitosan microparticles produced via ionicgelation with tripolyphosphate as a crosslinking agent. Prepared formulations were characterized and metoprololtartarate was loaded into the optimal blank microspheres. The entrapment efficiency, drug loading, cell viability assayand in vitro drug release were investigated. Optimum formulation was spherical and had 81% of yield and75.373±7.384μm particle size. 16 mg of metoprolol tartarate could be loaded into microparticles and drug release couldbe maintained for 48 hours.

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Makridakis S, DiNicolantonio JJ. Hypertension: empirical evidence and implications in 2014. Open Heart. 2014;1:e000048. doi:10.1136/openhrt-2014-000048.
Doğan AS, Yenicesu C, Sucaklı MH, Özdemir Ö, Demirel Y. Hipertansif hastaların ailelerinde Apo E gen polimorfizmleri ve kan lipit profillerinin değerlendirilmesi. Cumhuriyet Medical Journal. 2014; 36: 459-465.
Pinto1 IC, Martins D. Prevalence and risk factors of arterial hypertension: A literature review. J Cardiovasc Med Ther. 2017; 1(2): 1-7.
Laurent S. Antihypertensive drugs. Pharmacological Research .2017; 127: 116-125.
Wiysonge CS, Bradley HA, Volmink J, Mayosi BM, Opie LH. Beta-blockers for hypertension. Cochrane Database of Systematic Reviews. 2017; 1:1-93.
Özdemir L, Sümer H. The effect of educational intervention on blood pressure levels among hypertensive female patients aged over 30 and living in Sivas. Cumhuriyet Med J. 2009; 31: 31- 40.
Kushal M, Monali M, Durgavati M et al. Oral controlled release drug delivery system: an overview. International research journal of pharmacy. 2013; 4(3):70-76.
Moorthi C, Manavalan R, Kathiresan K. Nanotherapeutics to Overcome Conventional Cancer Chemotherapy Limitations. J Pharm Pharmaceut Sci. 2011; 14(1): 67-77.
Perrie Y, Rades T (eds). Controlling Drug Delivery. in Pharmaceutics - Drug Delivery and Targeting, 2nd edn. New Zealand: Pharmaceutical Press, 2012.
Prisant LM, Elliott WJ. Drug Delivery Systems for Treatment of Systemic Hypertension. Clin Pharmacokinet. 2003; 42 (11): 931-940.
Mothilal M, Nagalakshmi M, Swati PS et al. Optimisation and characetrisation of chitosan microspheres of aceclofenac. International Journal of Pharma Sciences and Research. 2012; 3(2): 305-315.
Stoica R, Şomoghi R, Ion RM. Preparation of chitosan – tripolyphosphate nanoparticles for the encapsulation of polyphenols extracted from rose hips. Digest Journal of Nanomaterials and Biostructures. 2013; 8(3): 955-963.
Sun Q, Han D, Lei H et al. Preparation and Characterization of Chitosan Microsphere Loading Bovine Serum Albumin. Journal of Wuhan University of Technology-Mater Sci Ed. 2012; 27(3): 459-464.
Patel KS, Patel MB. Preparation and evaluation of chitosan microspheres containing nicorandil. Int J Pharm Investig. 2014; 4(1): 32– 37.
Buiza OD, Dima C, Dima S. Preparation and characterization of chitosan microspheres for vancomycin delivey. Farmacia. 2015; 63(6): 897- 902.
Kumar K, Dhawan N, Sharma H et al. Bilayer mucoadhesive microparticles for the delivery of metoprolol succinate: Formulation and evaluation. Artificial Cells, Nanomedicine, and Biotechnology. 2014; 1–6.
Kunjachan S, Jose S, Lammers T. Understanding the mechanism of ionic gelation for synthesis of chitosan nanoparticles using qualitative techniques. Asian Journal of Pharmaceutics. 2010; 148-153.
Mitra A, Dey B. Chitosan Microspheres in Novel Drug Delivery Systems. Indian J Pharm Sci. 2011; 73(4): 355–366.
Demir GM, Değim IT. Preparation of Chitosan Nanoparticles by Nano Spray Drying Technology. FABAD J. Pharm. Sci. 2013; 38(3): 127-133.
Khan S, Gajbhiye C, Singhavi DJ, Yeole P. In situ Gel of Metoprolol Tartrate: Physicochemical Characterization, In vitro Diffusion and Histological Studies. Indian J Pharm Sci. 2012; 74(6): 564–570.