a Department of Chemical and Pharmaceutical Engineering, Faculty of Chemistry and Pharmacy , Sofia University , Sofia , Bulgaria.
Drug Dev Ind Pharm. 2018 Jul;44(7):1130-1138. doi: 10.1080/03639045.2018.1438461. Epub 2018 Feb 20.
To reveal the physicochemical mechanisms governing the solubilization of albendazole in surfactant and phospholipid-surfactant solutions and, on this basis, to formulate clinically relevant dose of albendazole in solution suitable for parenteral delivery.
(1) A new drug delivery system for parenteral delivery of albendazole is proposed, offering high drug solubility and low toxicity of the materials used; (2) New insights on the role of surface curvature on albendazole solubilization in surfactant and surfactant-phospholipid aggregates are provided.
The effect of 17 surfactants and 6 surfactant-phospholipid mixtures on albendazole solubility was studied. The size of the colloidal aggregates was determined by light-scattering. The dilution stability of the proposed formulation was assessed by experiments with model human serum.
Anionic surfactants increased very strongly drug solubility at pH = 3 (up to 4 mg/mL) due to strong electrostatic attraction between the oppositely charged (at this pH) drug and surfactant molecules. This effect was observed with all anionic surfactants studied, including sodium dodecyl sulfate, double chain sodium dioctylsulfosuccinate (AOT), and the bile salt sodium taurodeoxycholate. The phospholipid-surfactant mixture of 40% sodium dipalmitoyl-phosphatidylglycerol +60% AOT provided highest albendazole solubilization (4.4 mg/mL), smallest colloidal aggregate size (11 nm) and was stable to dilution with model human serum at (and above) 1:12 ratio.
A new albendazole delivery system with high drug load and low toxicity of the materials used was developed. The high solubility of albendazole was explained with vesicle-to-micelle transition due to the larger interfacial curvature preferred for albendazole solubilization locus.
揭示控制阿苯达唑在表面活性剂和磷脂-表面活性剂溶液中增溶的物理化学机制，并在此基础上配制适合于注射给药的临床相关剂量的阿苯达唑溶液。
（1）提出了一种新的阿苯达唑注射给药药物传递系统，该系统具有高药物溶解度和所用材料的低毒性；（2）提供了关于表面曲率在表面活性剂和表面活性剂-磷脂聚集体中对阿苯达唑增溶作用的新见解。
研究了 17 种表面活性剂和 6 种表面活性剂-磷脂混合物对阿苯达唑溶解度的影响。通过光散射法测定胶体聚集体的粒径。通过模型人血清实验评估所提出配方的稀释稳定性。
在 pH=3 时，阴离子表面活性剂（由于在该 pH 下药物和表面活性剂分子带相反电荷，因此存在强烈的静电吸引力）非常强烈地增加了药物的溶解度（高达 4mg/mL）。在所有研究的阴离子表面活性剂中均观察到这种效应，包括十二烷基硫酸钠、双链二辛基磺基琥珀酸钠（AOT）和胆汁盐牛磺脱氧胆酸钠。40%二棕榈酰基磷脂酰甘油+60%AOT 的磷脂-表面活性剂混合物提供了最高的阿苯达唑增溶度（4.4mg/mL）、最小的胶体聚集体尺寸（11nm），并且在 1:12 及以上的比例下与模型人血清稀释时稳定。
开发了一种新的阿苯达唑给药系统，该系统具有高药物载量和所用材料的低毒性。阿苯达唑的高溶解度可以通过由于更大的界面曲率而发生的囊泡-胶束转变来解释，这有利于阿苯达唑的增溶位置。
