Hot-Melt extrusion coupled with pressurized carbon dioxide for enhanced processability of pharmaceutical polymers and drug delivery applications - An integrated review.

Hot-melt extrusion (HME) technology is one of the primary approaches that has been implemented in recent years to overcome poor drug solubility/dissolution issues through the development of solid dispersion systems. Carbon dioxide (CO2) either in supercritical (SupC) or subcritical (SubC) forms has been introduced to HME as a temporary plasticizer, reducing the operating temperature and eventually processing heat-sensitive molecules more efficiently. In this paper, a comprehensive review of CO2-HME processes focused on pharmaceutical polymers and applications is presented. The steps and requirements for the setup of experimental devices are demonstrated, with a detailed influence of CO2 characteristics on HME processes. The most relevant physical and chemical properties of pharmaceutical grade polymers subjected to the CO2- HME process are described. The basic knowledge and main mechanisms of HME process parameters in conjunction with CO2 concentration with regard to process feasibility and final product formation are discussed. HME coupled with CO2 is extensively reviewed to provide a complete understanding of how to optimize the process parameters and conditions to reach optimized characteristics of final outcomes, as well as the sequential relationship between those outcomes (foaming → porosity → milling → tableting). Pharmaceutical applications of CO2-based HME are presented in detailed case studies, including extrusion feasibility, solubility, dissolution rate enhancement, and gastroretentive or floating drug delivery. Finally, the current status of general CO2-based techniques, as well as future perspectives and opportunities for promising applications through the integration of CO2 with HME is presented.

Application of Hot Melt Extrusion Technology in the Development of Abuse-Deterrent Formulations: An Overview.

The misuse, abuse, and illicit use of prescription opioid analgesics is a global public health concern. However, there are many viable therapeutic options for the treatment of patients with chronic pain. Both intact and manipulated opioid drug products are abused by various routes such as oral, nasal, and injection, which may lead to overdose, drug addiction, and even death. To combat the abuse of these medications, regulatory agencies and pharmaceutical companies are switching their interest towards developing Abuse Deterrent Formulations (ADFs), with the intent to deter the abuse of opioid products to a maximum extent. There are several manufacturing strategies implemented in an attempt to develop ADFs. An example includes matrix tablets of high molecular weight polymers such as polyethylene oxide. The scalable and continuous manufacturing techniques, such as Hot-Melt Extrusion (HME), is increasingly accepted by pharmaceutical companies to advance the development and manufacturing of ADFs. The application of the HME technique in the development of ADFs may overcome the challenges of opioid analgesic formulation development and provide improved protection against misuse and abuse, while also ensuring access to safe and effective use in patients with chronic pain. This review deals with a brief overview of strategies, with emphasis on HME to deter opioid abuse, in vitro characterization methods, commonly used excipients in the development of ADFs, and regulatory standards to meet the requirements of ADFs.