Rajesh A Michael, Popat Kiritkumar Mangaldas
Reverse Osmosis Membrane Division, Central Salt and Marine Chemicals Research Institute, Council of Scientific & Industrial Research (CSIR), G.B. Marg, Bhavnagar 364 002, India.
Academy of Scientific and Innovative Research, Central Salt and Marine Chemicals Research Institute, Council of Scientific & Industrial Research (CSIR), G.B. Marg, Bhavnagar 364 002, India.
J Pharm Anal. 2017 Aug;7(4):244-251. doi: 10.1016/j.jpha.2016.11.001. Epub 2016 Nov 12.
The objective of this study was to carry out taste masking of ofloxacin (Ofl) by ion exchange resins (IERs) followed by sustained release of Ofl by forming interpenetrating polymer network (IPN) beads. Drug-resin complexes (DRCs) with three different ratios of Ofl to IERs (1:1, 1:2, 1:4) were prepared by batch method and investigated for in vivo and in vitro taste masking. DRC of methacrylic acid-divinyl benzene (MD) resin and Ofl prepared at a ratio of 1:4 was used to form IPN beads. IPN beads of MD 1:4 were prepared by following the ionic cross-linking method using sodium carboxymethyl xanthan gum (SCMXG) and SCMXG-sodium carboxymethyl cellulose (SCMXG-SCMC). IPN beads were characterized with FT-IR and further studied on sustained release of Ofl at different pH. In vivo taste masking carried out by human volunteers showed that MD 1:4 significantly reduced the bitterness of Ofl. Characterization studies such as FT-IR, DSC, P-XRD and taste masking showed that complex formation took place between drug and resin. In vitro study at gastric pH showed complete release of drug from MD 1:4 within 30 min whereas IPN beads took 5 h at gastric pH and 10 h at salivary pH for the complete release of drug. As the crosslinking increased the release kinetics changed into non-Fickian diffusion to zero-order release mechanism. MD 1:4 showed better performance for the taste masking of Ofl and IPNs beads prepared from it were found useful for the sustained release of Ofl at both the pH, indicating a versatile drug delivery system.
本研究的目的是通过离子交换树脂（IERs）对氧氟沙星（Ofl）进行味觉掩蔽，然后通过形成互穿聚合物网络（IPN）珠实现Ofl的缓释。采用分批法制备了三种不同Ofl与IERs比例（1:1、1:2、1:4）的药物-树脂复合物（DRCs），并对其进行体内和体外味觉掩蔽研究。以1:4比例制备的甲基丙烯酸-二乙烯基苯（MD）树脂与Ofl的DRC用于形成IPN珠。采用羧甲基黄原胶钠（SCMXG）和SCMXG-羧甲基纤维素钠（SCMXG-SCMC），通过离子交联法制备了MD 1:4的IPN珠。用傅里叶变换红外光谱（FT-IR）对IPN珠进行了表征，并进一步研究了其在不同pH值下Ofl的缓释情况。人体志愿者进行的体内味觉掩蔽研究表明，MD 1:4显著降低了Ofl的苦味。FT-IR、差示扫描量热法（DSC）、粉末X射线衍射（P-XRD）等表征研究以及味觉掩蔽表明，药物与树脂之间形成了复合物。体外研究表明，在胃pH值下，MD 1:4中的药物在30分钟内完全释放，而IPN珠在胃pH值下需要5小时，在唾液pH值下需要10小时才能完全释放药物。随着交联度的增加，释放动力学从非菲克扩散转变为零级释放机制。MD 1:4在Ofl的味觉掩蔽方面表现出更好的性能，由其制备的IPN珠在两种pH值下对Ofl的缓释均有效，表明这是一种通用的药物递送系统。
