UGi-Pump® - An upper-GIT retention-enabling platform designed to provide with steady plasma drug concentration
Unmet Medical Need as a Driver for Innovative Products
Parkinson’s disease (PD) is the second most prevalent neurodegenerative disease, with estimted approximately 10 million population worldwide by 2030.
Levodopa (LD) is the mainstay for treatment of Parkinson's disease. But due to its short half-life, the current LD therapy necessitates multiple dosing, up to 8 times daily, which leads to substantial non-physiologic fluctuation of LD plasma concentrations, thereby exacerbating disease progression. The patients suffering advanced Parkinson's disease have a narrower therapeutic window that leads to “End of Dose Wearing off", “Peak-Dose Dyskinesia” and “High Levodopa Dose Burden". It's well believed that a steady LD plasma concentration (Continuous Dopaminergic Stimulation, CDS) can greatly mitigate the phenomenal symptoms, and even slow down the disease progression. Therefore, a therapy that can provide consistent levodopa plasma concentrations has become the all-sought goal for innovation of the delivery technologies.
Great Challenge to Slow Down Disease Progression
It’s a great challenge to develop an extended delivery technology for LD, since LD can be absorbed only at the upper gastrointestinal tract (UGIT) and the retention time of a conventional delivery system at UGIT is approximately 3-4 hrs.
An Innovative Delivery Technology
Realizing this unmet-medical need, WD Pharma has developed an innovative delivery technology called UGi-Pump® (Upper Gastrointestinal Pump).
UGi-Pump® is a controlled release system that can prolong the therapeutic coverage for the active pharmaceutical ingredients (API) that have their absorption window limited at the UGIT. As shown in Figure 1, UGi-Pump® is composed of two components, one being Extended-Release Platform (ERP) and the other Retention-Enabling Platform (REP). The REP functions to keep the ERP at the upper GI tract.
Figure 1. Two Components ofUGi-Pump®
Figure 2 is schematic representation of the configuration of the ERP. The proprietary high load/high flux ERP comprises a two-layer core (drug-containing Pull layer and osmotic Push layer), a rate-controlling membrane enclosing the core and optionally an immediate-release drug overcoat. A delivery orifice is laser-drilled through the membrane at the side of the drug-containing Pull layer. The ERP operates by imbibing water or moisture through the rate-controlling membrane into the bi-layer core, wherein it hydrates both layers, thereby causing the osmotic Push-layer to expand and push the hydrated, dispensable drug Pull-layer formulation through the orifice. The immediate-release drug overlayer of the ERP or immediate-release tablets comprising carbidopa/levodopa co-administrated with the ERP will provide a quick rising of the drug plasma concentration over its therapeutic level. The release profile of the ERP is not impacted by the environmental conditions, such as pH and agitation.
Figure 2. Configuration of Extended-Release Platform
UGi-Pump® is a non-invasive controlled delivery system that can provide a extended therapeutic coverage for 16-hour of waking time, with significantly reduced fluctuation of LD plasma concentration. UGi-Pump® is very stable with shelf-life at least two years at ambient conditions and can be readily handled by patients or their caregivers. Controlled release of LD utilizing UGi-Pump® will provide a very competitive and cost/effective option for treatment of advanced PD patients.
