Intrinsic lipolysis rate for systematic design of lipid-based formulations

Lipid-based formulations (LBFs) are used by the pharmaceutical industry in oral delivery systems for both poorly water-soluble drugs and biologics. Digestibility is key for the performance of LBFs and in vitro lipolysis is commonly used to compare the digestibility of LBFs. Results from in vitro lipolysis experiments depend highly on the experimental conditions and formulation characteristics, such as droplet size (which defines the surface area available for digestion) and interfacial structure. This study introduced the intrinsic lipolysis rate (ILR) as a surface area-independent approach to compare lipid digestibility.

The data contained in this dataset has been collected in the period from July 2021 until March 2022 at the Biomedical Center (BMC), Uppsala University.

The dataset contains two types of data: 1) dynamic light scattering (DLS) measurements of acylglycerol nanoemulsion droplets and 2) in vitro pH stat lipolysis data obtained from the digestion of acylglycerol nanoemulsions. 

Nineteen acylglycerol nanoemulsions were prepared with polysorbate 80 as stabilizer and digested in vitro. The experiments were conducted in triplicate. The data contained in this dataset is arranged in folders representing the nineteen acylglycerol nanoemulsions. The folder title gives information about the acylglycerol in the nanoemulsion and the concentration of polysorbate 80 used to stabilize the nanoemulsion. 

The hydrodynamic diameter of the nanoemulsion droplets was measured using a Litesizer 500 (Anton Paar, Graz, Austria). DLS measurements were conducted at 37 °C using the instrument’s automatic setting for adjustment of the focus and measurement angle. 

The in vitro pH stat lipolysis was conducted using a titrator (907 Titrando, Metrohm, Herisau, Switzerland) connected to a 10 ml burette, a pH electrode (iUnitrode with Pt 1000, Metrohm, Herisau, Switzerland) and a propeller stirrer. Lipolysis was conducted for 90 min using 0.6 M NaOH as the titrant when digesting nanoemulsions and 0.2 M NaOH when digesting the lipolysis medium (i.e., fasted state simulated intestinal fluid) without nanoemulsion (‘blank’). After lipolysis, the pH was rapidly raised to 9 to estimate the amount of unionized fatty acids (i.e., termed ‘back titration’; BT).

脂质基制剂（Lipid-based formulations, LBFs）已被制药工业广泛应用于难溶性药物与生物制剂的口服递送系统中。消化特性是决定脂质基制剂性能的核心关键，而体外脂解实验通常被用于比较不同脂质基制剂的消化能力。体外脂解实验的结果高度依赖于实验条件与制剂自身特性，例如液滴尺寸（决定了可供脂解反应进行的表面积）以及界面结构。本研究提出了固有脂解速率（Intrinsic Lipolysis Rate, ILR）这一不依赖表面积的分析方法，用于标准化比较脂质的消化能力。

本数据集收录的数据采集于2021年7月至2022年3月，采集地点为乌普萨拉大学生物医学中心（Biomedical Center, BMC）。

本数据集包含两类数据：1）酰基甘油纳米乳液滴的动态光散射（Dynamic Light Scattering, DLS）表征数据；2）通过酰基甘油纳米乳体外消化实验获得的pH稳态脂解数据。

本研究共制备19种以聚山梨酯80为稳定剂的酰基甘油纳米乳，并对其开展体外消化实验，所有实验均设置三次重复。本数据集的数据按照对应19种酰基甘油纳米乳的文件夹进行组织，文件夹名称包含了纳米乳中酰基甘油的种类以及用于稳定纳米乳的聚山梨酯80浓度信息。

采用Litesizer 500型粒度仪（安东帕公司，奥地利格拉茨）对纳米乳液滴的流体动力学直径进行表征。动态光散射实验均在37℃下开展，仪器自动调整聚焦参数与测量角度。

体外pH稳态脂解实验采用连接有10mL滴定管、pH电极（带Pt 1000的iUnitrode电极，瑞士万通公司，黑里绍）与桨式搅拌器的滴定仪（907 Titrando，瑞士万通公司，黑里绍）完成。脂解实验总时长为90分钟：消化纳米乳时采用0.6 M氢氧化钠作为滴定剂，而消化不含纳米乳的脂解介质（即空腹状态模拟肠液，又称"空白组"）时则采用0.2 M氢氧化钠。脂解反应结束后，快速将体系pH调至9，以估算未电离脂肪酸的总量，该步骤又称"回滴（Back Titration, BT）"。