Rapid Delivery of Therapeutics Via Dissolution of Polymeric Films

口服给药是最常见的给药形式，以各种形式的片剂和胶囊的使用为主。然而，与片剂相关的一些问题削弱了这种给药形式的效用。例如，吞咽困难的患者（儿童、老人、严重恶心的人和患有吞咽困难的患者）不能耐受固体药片。此外，药片必须通过胃肠道，治疗药物通过肠道被吸收。这需要大量的时间，延迟治疗行动的开始。最后，吞下的药物通常会进行代谢，并可能导致肝毒性。作为片剂的替代品，在口腔中迅速溶解的聚合物薄膜受到了极大的关注。这些薄膜被辉瑞公司以李斯德林PocketPaks的名字引入市场，自2001年以来一直是一种受欢迎的口气清新剂。然而，这些薄膜也可以装载药物制剂用于口服药物输送。这使得治疗剂量在口腔中释放，并通过粘膜被吸收直接进入血液，绕过胃和肝脏。这是有利的，因为它导致药物快速进入循环，绕过胃肠道代谢，减少肝毒性，并且不需要吞咽。然而，在快速溶解的聚合物薄膜中装载不同的药物化合物，特别是那些不溶于水的药物，会带来挑战，因为不同的结构会影响薄膜的完整性和性能。该提案旨在研究在聚合物薄膜内结合和封装各种药物的新配方，并帮助工业合作伙伴（Rapid Dose Therapeutics, Inc.）为制药行业开发替代的递送方法。

Oral delivery of pharmaceuticals is the most common form of drug administration, and is dominated by the use of tablets and capsules of various forms. However, there are a number of problems associated with tablets that diminish the utility of this form of dose administration. For instance, patients that have difficulty swallowing (children, the elderly, people with severe nausea, and patients suffering from dysphasia) are unable to tolerate solid tablets. In addition, tablets must pass through the gastrointestinal tract, with the therapeutic agents being absorbed through the gut. This takes significant amounts of time, delaying the onset of therapeutic action. Finally, drugs that are swallowed generally undergo metabolism, and can cause liver toxicity. As an alternative to tablets, thin polymer films that rapidly dissolve in the mouth have received significant attention. These films have been introduced in the market by Pfizer as Listerine PocketPaks, and have been a popular breath freshener since 2001. However, these films can also be loaded with pharmaceutical agents for oral drug delivery. This allows a therapeutic dose to be released in the mouth, and to be absorbed through the mucosal membranes directly into the bloodstream, bypassing the stomach and liver. This is advantageous as it results in rapid entry of drugs into circulation, bypasses gastrointestinal metabolism, decreases liver toxicity, and does not require swallowing. However, loading different drug compounds, especially those that are not water soluble, within a rapidly dissolving thin polymer film poses challenges, as different structures will impact film integrity and properties. This proposal aims to investigate new formulations for incorporation and encapsulation of a wide array of drugs within polymer films, and to help the industrial partner (Rapid Dose Therapeutics, Inc.) develop alternative delivery methods for the pharmaceutical industry.