Kalicharan R W, Oussoren C, Schot P, de Rijk E, Vromans H
Department of Clinical Pharmacy, Division of Laboratory & Pharmacy, University Medical Center Utrecht, P/O Box 85500, 3508 GA Utrecht, the Netherlands; Department of Pharmaceutics, UIPS, Utrecht University, PO Box 80082, 3508 TB Utrecht, The Netherlands.
Department of Pharmaceutics, UIPS, Utrecht University, PO Box 80082, 3508 TB Utrecht, The Netherlands.
Int J Pharm. 2017 Aug 7;528(1-2):595-601. doi: 10.1016/j.ijpharm.2017.06.055. Epub 2017 Jun 17.
Sustained release of lipophilic compounds can be achieved with oil depots. These parenteral formulations are generally injected in the vastus lateralis and deltoid muscle. It is known that the absorption rate differs between these two muscles. The reason for this is not fully understood. The aim of the current study was to investigate the fate of an oil depot in different tissues to elucidate whether the disappearance rate of oil is the cause of observed differences in absorption rate. A study with healthy volunteers was conducted to determine 1.0mL oil depots in the vastus lateralis and deltoid muscle for two weeks. The spatial distribution of the oil depots was determined using MRI. Additionally, a study in rats was conducted to microscopically examine the oil immediately and after 31days of injection. All rats were injected with a 0.1mL oil depot with and without benzyl alcohol (BOH), a commonly used excipient in oil depots. In humans, it was shown that all oil depots were equal in volume and surface area directly after injection. Moreover, the disappearance rate for all oil depots was similar; within one week there was no depot visible anymore by MRI. This in contrast to the depots in rats, which were still microscopically visible after 31days. It is concluded from these observations that the oil is dispersed to small droplets in the course of time. The resulting increase in surface area does not lead to an increase in absorption rate however. The results of this paper show that the variation in drug absorption as found for the two muscles is not caused by a distinction in surface areas or disappearance rates of the oil depots. Therefore, it is argued that the local tissue drainage (e.g. lymph flow) plays a considerable role in drug absorption from oil depots, whereby the lymph flow differs between the muscles.
油库可实现亲脂性化合物的缓释。这些肠胃外制剂通常注射到股外侧肌和三角肌中。众所周知，这两块肌肉的吸收速率有所不同。其原因尚未完全明确。本研究的目的是调查油库在不同组织中的转归，以阐明油的消失速率是否是观察到的吸收速率差异的原因。对健康志愿者进行了一项研究，以确定在股外侧肌和三角肌中注射1.0mL油库两周后的情况。使用磁共振成像（MRI）确定油库的空间分布。此外，还对大鼠进行了一项研究，在注射后立即和31天后对油进行显微镜检查。所有大鼠均注射了含和不含苯甲醇（BOH，油库中常用的辅料）的0.1mL油库。在人体中，结果显示注射后所有油库的体积和表面积均相等。此外，所有油库的消失速率相似；一周内MRI已无法再看到任何油库。这与大鼠中的油库形成对比，大鼠中的油库在31天后通过显微镜仍可见。从这些观察结果可以得出结论，随着时间的推移，油会分散成小液滴。然而，由此导致的表面积增加并未导致吸收速率增加。本文的结果表明，两块肌肉中发现的药物吸收差异并非由油库的表面积或消失速率差异所致。因此，有人认为局部组织引流（如淋巴液流动）在油库药物吸收中起相当大的作用，而两块肌肉中的淋巴液流动有所不同。
