Joshi Prachi, Mallepogu Prabhakar, Kaur Harpreet, Singh Ridhima, Sodhi Ikjot, Samal Sanjaya K, Jena Kailash C, Sangamwar Abhay T
Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Sahibzada Ajit Singh Nagar, Punjab 160062, India.
Department of Physics, Indian Institute of Technology, Ropar, Rupnagar, Punjab 140001, India.
Eur J Pharm Sci. 2021 Dec 1;167:106014. doi: 10.1016/j.ejps.2021.106014. Epub 2021 Oct 10.
Supersaturation as a formulation principle relates to the aqueous solubility of poorly soluble drugs in solution . However, supersaturation state of drugs tends to crystallize because of its thermodynamic instability thereby compromising the solubility and biopharmaceutical performance of drugs. The present study aims to investigate the supersaturation potential of albendazole (ABZ) and its precipitation via nucleation and crystal growth. We hypothesized the use of polymers will avoid ABZ precipitation by interacting with drug molecules. The drug polymer interactions are characterized using conventional methods of Fourier transform infrared (FTIR), Nuclear magnetic resonance (NMR) and Polarized light microscopy (PLM). We have used a novel approach of sum frequency generation (SFG) vibrational spectroscopic in exploring the drug polymer interactions at air-water interface. Recently we have reported the SFG for e rifaximin-polymer interactions (Singh et al., 2021). The supersaturation assay, saturation solubility studies and nucleation induction time analysis revealed polyvinyl alcohol (PVA) and polyvinyl pyrrolidone (PVP K30) as effective precipitation inhibitors thereby enhancing the ABZ equilibrium solubility and in vitro supersaturation maintenance of ABZ. Further, modification in the solid state of ABZ has confirmed the influence of polymers on its precipitation behaviour. We conclude that PVA and PVP K30 act as nucleation and crystal growth inhibitor, respectively for the precipitation inhibition of ABZ.
过饱和作为一种制剂原理，与难溶性药物在溶液中的水溶性相关。然而，药物的过饱和状态因其热力学不稳定性而易于结晶，从而损害药物的溶解度和生物药剂学性能。本研究旨在探究阿苯达唑（ABZ）的过饱和潜力及其通过成核和晶体生长的沉淀过程。我们假设使用聚合物将通过与药物分子相互作用来避免ABZ沉淀。使用傅里叶变换红外光谱（FTIR）、核磁共振（NMR）和偏光显微镜（PLM）等传统方法对药物-聚合物相互作用进行表征。我们采用和频产生（SFG）振动光谱这一新颖方法来探究气-水界面处的药物-聚合物相互作用。最近我们报道了利福昔明-聚合物相互作用的SFG（Singh等人，2021年）。过饱和测定、饱和溶解度研究和成核诱导时间分析表明，聚乙烯醇（PVA）和聚乙烯吡咯烷酮（PVP K30）是有效的沉淀抑制剂，从而提高了ABZ的平衡溶解度以及ABZ在体外的过饱和维持能力。此外, ABZ固态的改变证实了聚合物对其沉淀行为的影响。我们得出结论，PVA和PVP K30分别作为成核抑制剂和晶体生长抑制剂来抑制ABZ的沉淀。
