Irfan Jaffar, Ali Arshad, Hussain Muhammad Ajaz, Haseeb Muhammad Tahir, Naeem-Ul-Hassan Muhammad, Hussain Syed Zajif
Institute of Chemistry, University of Sargodha Sargodha 40100 Pakistan.
Centre for Organic Chemistry, School of Chemistry, University of the Punjab Lahore 54590 Pakistan
RSC Adv. 2024 Mar 7;14(12):8018-8027. doi: 10.1039/d4ra00095a. eCollection 2024 Mar 6.
The current research work is based on the evaluation of a citric acid (CA) cross-linked ( M.) leaf hydrogel (CL-ALH) for pH-dependent and sustained drug release application. The CA was used in different concentrations (1.25, 2.5, 5.0, and 10.0%) to cross-link the ALH using homogenous reaction conditions. The synthesis of CL-ALH was confirmed through Fourier transform and nuclear magnetic resonance spectroscopic studies. The thermal analysis indicated that the ALH and CL-ALH were stable and decomposed in two steps. The scanning electron microscopic images of CL-ALH confirmed its porous nature due to the presence of interconnected channeling. The swelling of CL-ALH was evaluated at pH 1.2, 6.8, and 7.4 as well as in deionized water (DW). High swelling of CL-ALH was observed in DW, and at pH 7.4 and 6.8 whereas, less swelling of CL-ALH was witnessed at pH 1.2. CL-ALH also exhibited swelling/deswelling behavior in DW and ethanol, DW and normal saline, and at pH 7.4 and 1.2. Tablets were prepared from CL-ALH as a release retarding agent demonstrating the sustained release of venlafaxine hydrochloride (VFX) for 8 h. Whereas, VFX was released within 4 h from the ALH-based tablet formulation (un-cross-linked material) indicating the prolonged and sustained release behavior of CL-ALH. The VFX was released from CL-ALH tablets and followed zero-order kinetics. The mechanism followed by VFX release from CL-ALH tablets was non-Fickian diffusion. The fate of the tablet formulation was observed through an X-ray study. The CL-ALH-based tablet safely passed through the stomach of a stray dog without any significant erosion and then disintegrated in the small intestine and colon. These findings confirmed that the CL-ALH is an effective excipient for designing a sustained-release drug delivery system for the small intestine and colon.
当前的研究工作基于对柠檬酸（CA）交联的（M.）叶水凝胶（CL-ALH）用于pH依赖性和持续药物释放应用的评估。使用不同浓度（1.25%、2.5%、5.0%和10.0%）的CA在均相反应条件下交联ALH。通过傅里叶变换和核磁共振光谱研究证实了CL-ALH的合成。热分析表明，ALH和CL-ALH是稳定的，并且分两步分解。CL-ALH的扫描电子显微镜图像证实了由于存在相互连接的通道，其具有多孔性质。在pH 1.2、6.8和7.4以及去离子水（DW）中评估了CL-ALH的溶胀情况。在DW、pH 7.4和6.8时观察到CL-ALH的高溶胀，而在pH 1.2时CL-ALH的溶胀较小。CL-ALH在DW和乙醇、DW和生理盐水以及pH 7.4和1.2时也表现出溶胀/消溶胀行为。以CL-ALH作为释放阻滞剂制备了片剂，证明盐酸文拉法辛（VFX）持续释放8小时。而VFX在4小时内从基于ALH的片剂制剂（未交联材料）中释放，表明CL-ALH具有延长和持续释放行为。VFX从CL-ALH片剂中释放并遵循零级动力学。VFX从CL-ALH片剂中释放所遵循的机制是非菲克扩散。通过X射线研究观察了片剂制剂的命运。基于CL-ALH的片剂安全地通过了一只流浪狗的胃，没有任何明显的侵蚀，然后在小肠和结肠中崩解。这些发现证实，CL-ALH是设计用于小肠和结肠的缓释药物递送系统的有效辅料。
