College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL 33328, United States.
College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL 33328, United States.
Eur J Pharm Sci. 2021 Nov 1;166:105965. doi: 10.1016/j.ejps.2021.105965. Epub 2021 Aug 8.
Oral drug delivery is often challenged with enzymatic degradation of drug molecules in the gastrointestinal tract and high first-pass metabolism, resulting in low bioavailability. Delivery of drug molecules via the oral cavity mucosa is considered a viable option to enhance bioavailability. One of the relatively new dosage forms for transmucosal drug delivery is the oral thin film (OTF) with mucoadhesive properties that offers several advantages over conventional dosage forms, including faster dissolution, higher patient compliance, and extended oral retention by reduced salivary washout. Mucoadhesive OTFs should have sufficient muco-adhesiveness as well as suitable mechanical properties for their best performance, thus such characterization is critical in the successful design and development of OTFs. However, there is currently no FDA or USP-recommended analytical procedure or standard available for evaluating adhesiveness and mechanical properties of mucoadhesive OTFs. Therefore, we aimed to develop a fast and reliable in vitro method capable of differentiating various OTFs in terms of their adhesive strengths using a texture analyzer. We found that an in vitro gel substrate composed of 4% w/v gellan gum and 2% w/v glycerin could be used to discriminate between the adhesive features of the tested film samples. Also, our studies show that the adhesion test parameters of 0.96 N target force, probe speed of 0.1 mm/s, holding time of 15 s, and conditioning medium volume of 200 μL while using the said substrate could successfully differentiate between the adhesion strength of the OTF samples. We further examined the film samples for their physicomechanical properties to obtain a tangible and practical range of mechanical values for pharmaceutical OTFs using the puncture test and folding endurance test. We found a breaking factor above 34.5 N/mm, elongation to puncture less than 5.55% and folding endurance of at least 50 folds can be used as a starting point when designing and manufacturing OTFs.
口服给药常常面临药物分子在胃肠道中被酶降解以及首过代谢高的挑战，导致生物利用度低。通过口腔黏膜给药被认为是提高生物利用度的可行选择。经口腔黏膜给药的相对较新剂型之一是具有黏膜黏附特性的口腔薄膜（OTF），与传统剂型相比，它具有几个优势，包括更快的溶解、更高的患者依从性以及通过减少唾液冲洗而延长的口腔滞留时间。具有黏膜黏附性的 OTF 应该具有足够的黏膜黏附性以及适合的机械性能，以实现最佳性能，因此这种特性分析对于 OTF 的成功设计和开发至关重要。然而，目前尚无 FDA 或 USP 推荐的分析程序或标准可用于评估黏膜黏附性 OTF 的黏附性和机械性能。因此，我们旨在开发一种快速可靠的体外方法，使用质地分析仪根据其黏附强度来区分各种 OTF。我们发现，由 4% w/v 结冷胶和 2% w/v 甘油组成的体外凝胶基质可用于区分测试薄膜样品的黏附特征。此外，我们的研究表明，使用所述基质时，0.96 N 目标力、探针速度 0.1 mm/s、保持时间 15 s 和条件介质体积 200 μL 的黏附测试参数可以成功区分 OTF 样品的黏附强度。我们进一步检查了薄膜样品的物理机械性能，使用穿刺试验和耐折试验为药用 OTF 获得了切实可行的机械值范围。我们发现，断裂因子高于 34.5 N/mm、穿刺伸长率小于 5.55%和至少 50 次折叠耐力可以作为设计和制造 OTF 的起点。
