自乳化药物传递系统：一种通过疏水离子对提高 BCS 类 III 药物口服传递的多功能方法。
Self-emulsifying drug delivery systems: A versatile approach to enhance the oral delivery of BCS class III drug via hydrophobic ion pairing.
机构信息
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Faisalabad, Pakistan.
Department of Pharmacy, Hazara University, Mansehra, Pakistan.
出版信息
PLoS One. 2023 Jun 9;18(6):e0286668. doi: 10.1371/journal.pone.0286668. eCollection 2023.
Biopharmaceutical classification systems (BCS) class III drugs belongs to a group of drugs with high solubility in gastrointestinal (GI) fluids and low membrane permeability result in significantly low bioavailability. Self-emulsifying drug delivery systems (SEDDS) considered a suitable candidate to enhance the bioavailability of poorly soluble drugs by improving their membrane permeability, however, incorporating hydrophilic drugs in to these carriers remained a great challenge. The aim of this study was to develop hydrophobic ion pairs (HIPs) of a model BCS class-III drug tobramycin (TOB) in order to incorporate into SEDDS and improve its bioavailability. HIPs of TOB were formulated using anionic surfactants sodium docusate (DOC) and sodium dodecanoate (DOD). The efficiency of HIPs was estimated by measuring the concentration of formed complexes in water, zeta potential determination and log P value evaluation. Solubility studies of HIPs of TOB with DOC were accomplished to screen the suitable excipients for SEDDS development. Consequently, HIPs of TOB with DOC were loaded into SEDDS and assessed the log DSEDDS/release medium and dissociation of these complexes at different intestinal pH over time. Moreover, cytotoxic potential of HIPs of TOB and HIPs loaded SEDDS formulations was evaluated. HIPs of TOB with DOC exhibited the maximum precipitation efficiency at a stoichiometric ratio of 1:5. Log P of HIPs of TOB improved up to 1500-fold compared to free TOB. Zeta potential of TOB was shifted from positive to negative during hydrophobic ion pairing (HIP). HIPs of TOB with DOC was loaded at a concentration of 1% (w/v) into SEDDS formulations. Log DSEDDS/release medium of loaded complexes in to oily droplets was above 2 and dissociated up to 20% at various pH within 4 h. Finding of this study suggested that improvement of the lipophilic character of BCS class-III drugs followed by incorporation into oily droplets can be deliberated as a promising tool to enhance the permeation across biological membranes.
生物制药分类系统（BCS）III 类药物属于一组在胃肠道（GI）流体中具有高溶解度但膜通透性低的药物，导致生物利用度显著降低。自乳化药物传递系统（SEDDS）被认为是一种通过提高其膜通透性来提高难溶性药物生物利用度的合适候选药物，然而，将亲水性药物纳入这些载体仍然是一个巨大的挑战。本研究旨在开发模型 BCS 类 III 药物妥布霉素（TOB）的疏水离子对（HIP），以便将其纳入 SEDDS 并提高其生物利用度。使用阴离子表面活性剂十二烷基硫酸钠（DOC）和月桂酸钠（DOD）制备 TOB 的 HIP。通过测量水中形成的复合物的浓度、测定zeta 电位和评估 log P 值来估计 HIP 的效率。完成了 TOB 与 DOC 的 HIP 的溶解度研究，以筛选用于 SEDDS 开发的合适赋形剂。因此，将 TOB 与 DOC 的 HIP 载入 SEDDS，并评估不同肠道 pH 下不同时间这些复合物的 log DSEDDS/释放介质和解离。此外，还评估了 TOB 的 HIP 和 HIP 负载 SEDDS 制剂的细胞毒性潜力。TOB 与 DOC 的 HIP 在化学计量比为 1:5 时表现出最大的沉淀效率。与游离 TOB 相比，TOB 的 HIP 的 log P 提高了 1500 倍。TOB 的 zeta 电位在疏水离子配对（HIP）过程中从正变为负。将 TOB 与 DOC 的 HIP 以 1%（w/v）的浓度载入 SEDDS 制剂中。负载复合物在油滴中的 log DSEDDS/释放介质大于 2，在 4 小时内各种 pH 下解离达 20%。本研究的结果表明，提高 BCS 类 III 药物的亲脂性，然后将其纳入油滴中，可以被视为一种提高跨生物膜渗透的有前途的工具。
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