Multi-day Pain Management Therapy with Novel Injectable Formulation

描述（由申请人提供）：我们的长期目标是广泛使用PPF技术，以促进具有均匀大小和物理特性的药物包封微颗粒的有效生产，这些微颗粒可以在单次给药后以可控的速率在体内数天内释放特定药物。对于这项提议，我们特别针对成本和剂量有效的慢性疼痛管理，精确定制药物释放特性。在美国，慢性疼痛折磨着很多人。更安全的（计划外）阿片类药物的缓释制剂可以提高患者的依从性和药物疗效，并可以限制突破性疼痛的可能性，所有这些都不会使患者面临成瘾的风险。然而，现有的缓释阿片类药物制剂是不够的，并且仅限于提供最多24小时的缓解。使用曲马多，一种计划外的阿片类药物，该项目旨在创造一种长效（长达5天）的曲马多注射剂制剂，以增强疼痛缓解，填补制药市场的关键创新空白。本应用程序的具体目的是优化PPF技术生产的负载曲马多的微球，具有5天零级药物释放曲线，模拟恒定输注泵样给药（specific Aim 1），并验证曲马多缓释制剂在体内获得的结果（specific Aim 2）。我们的总体假设是，使用PPF技术生产的均匀微球开发的扩展疼痛管理疗法将提供成本和剂量有效的慢性疼痛管理，具有精确定制的药物释放特性，与使用传统方法制造的曲马多负载微球相比，它将提供更可控和可预测的药物释放。与当代市售的缓释疼痛管理产品（如ULTRAM(R)）相比，显著改善了可控释放特性。多日慢性疼痛管理治疗有可能为疼痛管理提供革命性的替代方案。

DESCRIPTION (provided by applicant): Our long term goal is to widespread the use of PPF technology for promoting effective production of drug-encapsulating microparticles with uniform size and physical characteristics that can be leveraged to release a specific drug at controlled rates over multi-day periods in vivo after a single administration. For this proposal, we are specifically targeting a cost and dose-effective management of chronic pain with precisely tailored drug release characteristics. Chronic pain afflicts a large population in United States. Extended release formulations of safer (unscheduled) opioids can improve patient compliance and drug efficacy, and can limit the possibility of breakthrough pain, all without putting the patients at the risk of addiction. However, existing extended release opioid formulations are insufficient, and are limited to providing relief up to a maximum of 24 h. Using tramadol, an unscheduled opioid, this project aims to create a long-acting (up to 5-day) tramadol formulation in an injectable form to enhance pain relief and fill a critical innovation gap in the pharmaceutical market. The specific objective of this application is to optimize tramadol-loaded microspheres produced by PPF technology with a 5 day zero-order drug release profiles, imitating a constant infusion pump-like dosing (Specific Aim 1), and validate the results achieved with extended release formulations of tramadol in vivo (Specific Aim 2). Our overall hypothesis is that extended pain management therapy developed using uniform microspheres produced by PPF technology will offer a cost and dose-effective management of chronic pain with precisely tailored drug release characteristics, which will provide a more controlled and predictable drug release compared to tramadol-loaded microspheres fabricated using conventional methods, and significantly improve controlled release characteristics compared to contemporary commercially-available sustained-release pain management products (e.g., ULTRAM(R)). Multi-day chronic pain management therapy holds the potential to provide a revolutionary alternative for pain management. PUBLIC HEALTH RELEVANCE: Chronic pain afflicts a large population in United States. Extended release formulations of safer (unscheduled) opioids can improve patient compliance and drug efficacy, and can limit the possibility of breakthrough pain, all without putting the patients at the risk of addiction. However, existing extended release opioid formulations are insufficient, and are limited to providing relief up to a maximum of 24 h. Using tramadol, an unscheduled opioid, this project aims to create a long- acting (up to 5-day) tramadol formulation in an injectable form to enhance pain relief and fill a critical innovation gap in the pharmaceutical market.