Universidade Federal de Pernambuco, Departamento de Ciências Farmacêuticas, CEP: 50740-520 Recife, PE, Brazil.
University of Bath, Department of Pharmacy & Pharmacology, Claverton Down, Bath BA2 7AY, UK.
Int J Pharm. 2018 Apr 25;541(1-2):167-172. doi: 10.1016/j.ijpharm.2018.02.032. Epub 2018 Feb 17.
The topical bioavailabilities of metronidazole from a commercially available 'reference' product (Rozex®) and two extemporaneous test formulations were compared. With the reference drug product, a full skin pharmacokinetic profile, in vivo in human volunteers (following a 6-h uptake and clearance over the subsequent 22 h), was obtained using an improved stratum corneum (SC) sampling procedure. Then, a two-time point SC sampling method enabled the bio(in)equivalence of the test formulations to Rozex® to be evaluated. One test formulation was shown to be bioequivalent to Rozex®, both for uptake and clearance, whereas the other (more viscous and less spreadable) formulation was not. The delivery of metronidazole into the underlying viable epidermal tissue from Rozex® and from the equivalent test formulation was 2.5 to 3.5-fold higher than that from the inequivalent extemporaneous vehicle. The results highlight that the quantitative composition of a formulation, as well as its physical properties that influence events that take place at the vehicle-skin interface, can have a dramatic impact on the delivery of drug into the SC and subsequently to the viable skin layers below. The reproducible, sensitive and facile in vivo methodology employed may prove of particular value where regulatory approval of generic formulations lacks objective rigour.
比较了市售“参比”产品（Rozex®）和两种临时测试制剂的甲硝唑的局部生物利用度。使用改进的角质层（SC）取样程序，从人体志愿者（经过 6 小时的吸收和随后 22 小时的清除）获得了参比药物产品的完整皮肤药代动力学特征。然后，采用两次 SC 取样方法评估了测试制剂与 Rozex®的生物等效性。结果表明，一种测试制剂在吸收和清除方面与 Rozex®具有生物等效性，而另一种（粘性更大、更不易扩散）制剂则不具有生物等效性。Rozex®和等效测试制剂将甲硝唑递送至下面的有活力的表皮组织的量是来自不等效临时载体的 2.5 至 3.5 倍。结果表明，制剂的定量组成以及影响发生在载体-皮肤界面的物理性质，可以对药物递送至 SC 以及随后递送至下面有活力的皮肤层产生巨大影响。所采用的可重现、灵敏且简便的体内方法可能在缺乏客观严格性的情况下对通用配方的监管批准具有特殊价值。
