Division of Pharmaceutical Manufacturing II, Office of Pharmaceutical Manufacturing Assessment, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, Maryland, USA.
Division of Product Quality Research, Office of Testing and Research, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, Maryland, USA.
Int J Pharm. 2020 Mar 30;578:119132. doi: 10.1016/j.ijpharm.2020.119132. Epub 2020 Feb 10.
This study investigated the effects of drug recrystallization on the in vitro performance of testosterone drug-in-adhesive transdermal delivery system (TDS). Six formulations were prepared with a range of dry drug loading in the adhesive matrix from 1% to 10% w/w with the aim of generating TDS with various levels of drug crystals. We visually quantified the amount of crystals in TDS by polarized light microscopy. The effect of drug recrystallization on adhesion, tackiness, cohesive strength, viscoelasticity, drug release, and drug permeation through human cadaver skin were evaluated for these TDS samples. The Optical images showed no crystals in 1% and 2% testosterone TDSs; however, the amount of crystals increased by increasing testosterone loading from 4 to 10%. A proportional and significant decrease (p < 0.05) in tack, peel, and shear strength of the adhesive matrix with increasing amount of crystals in TDS was observed. The drug crystals resulted in a proportional deterioration of the viscoelastic properties of the adhesive matrix. The 2% testosterone TDS showed faster drug release rate when compared to 1% testosterone TDS. The increase in drug loading from 2% to 4% w/w slightly increased the cumulative amount of testosterone released. Further increase in drug loading in TDS to 6, 8, and 10% was nonsignificant (p > 0.05) to affect the drug release and permeation. In conclusion, this study demonstrated that the extent of drug recrystallization can be quantitatively correlated with the deterioration of performance characteristics of TDS products.
本研究考察了药物重结晶对睾酮贴剂透皮给药系统（TDS）体外性能的影响。制备了六种制剂，其在粘合剂基质中的干药物载量范围为 1%至 10%w/w，旨在生成具有不同药物晶体水平的 TDS。我们通过偏光显微镜对 TDS 中的晶体量进行了直观的定量。评估了这些 TDS 样品中药物重结晶对粘合性、粘性、内聚强度、粘弹性、药物释放和药物透过人体尸体皮肤的影响。光学图像显示 1%和 2%睾酮 TDS 中没有晶体；然而，随着睾酮负载量从 4%增加到 10%，晶体数量增加。观察到随着 TDS 中晶体数量的增加，粘合基质的粘性、剥离和剪切强度呈比例显著降低（p<0.05）。药物晶体导致粘合基质的粘弹性呈比例恶化。与 1%睾酮 TDS 相比，2%睾酮 TDS 显示出更快的药物释放速率。药物负载从 2%增加到 4%w/w 时，释放的睾酮累积量略有增加。进一步增加 TDS 中的药物负载至 6%、8%和 10%对药物释放和渗透没有显著影响（p>0.05）。总之，本研究表明药物重结晶的程度可以与 TDS 产品性能特征的恶化定量相关。
