Karvedilolun Çözünürlüğünü Arttırıcı Olarak Jeffamine® Çekirdekli PAMAM Dendrimerler

Year 2019, , 130 - 138, 01.03.2019

Ali Serol Ertürk , Mustafa Ulvi Gürbüz , Metin Tülü , Abdürrezzak Emin Bozdoğan

https://doi.org/10.21597/jist.430007

Abstract

Bu çalışmada amacımız Jeffamine® çekirdekli PAMAM dendrimerlerin, biyofarmasötik sınıflandırma sistemi sınıf II ilacı ve alfa 1 engelleyici aktivite ile seçici olmayan bir beta-adrenerjik bloke edici ajan olan karvedilol’ün (CAR) sudaki çözünürlüğü üzerindeki etkisini araştırmaktır. CAR'ın sudaki çözünürlüğü, geleneksel döner şişe tekniği kullanılarak fosfat tamponlu tuz içinde oda sıcaklığında dendrimerler varlığında ölçüldü. Faz çözünürlük çalışmalarından elde edilen sonuçlar, CAR'ın sudaki çözünürlüğünü, dendrimer konsantrasyonuyla neredeyse orantılı olduğunu ve PAMAM dendrimerlerin mevcudiyetinde önemli ölçüde arttığını gösterdi. Bu çalışmalar gösterdi ki, PAMAM dendrimerlerin CAR'nin çözünürlüğünü arttırıcı olarak düşünülebileceğini ve çeşitli formülasyonların geliştirilmesine yardımcı olabileceğini gösterdi.

Keywords

Çözündürme, ilaç bağlama sabiti, karvedilol, kompleks, PAMAM dendrimer

Jeffamine® Core PAMAM Dendrimers as Solubility Enhancer of Carvedilol

Abstract

The aim of this study was to investigate the effect of Jeffamine® core poly(amidoamine) PAMAM dendrimers (JCPDs) on the aqueous solubility of carvedilol (CAR), a Biopharmaceutical Classification System (BCS) Class II drug, and a nonselective beta-adrenegenic blocking agent with alpha 1-blocking activity. The aqueous solubility of CAR was measured in the presence of JCPDs at room temperature in phosphate-buffered saline using traditional rotating bottle technique. Results obtained from the phase solubility studies revealed that the molar aqueous solubility of CAR increased significantly with a proportional increase in the concentration of fourth-generation JCPD, P4.NH₂. Likewise, the encapsulation efficiency of JCPD, P4.NH₂ improved as its concentration increased and the highest capacity was observed to be 60.75%. Furthermore, the drug binding constant of P4.NH₂ (11177.31 ± 0.15 M^-1) was found to be fifty times higher than that of β-cyclodextrin (227 M^-1), which is the most common studied solubility enhancer excipient for CAR drug. Overall, it can be concluded that PAMAMs, used for the first time in this study as the successful solubility enhancer of CAR, might be helpful and good candidates for the development of various formulations in the future studies.

Keywords

Carvedilol, complexation, drug binding constant, PAMAM dendrimer, Jeffamine

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