Development of a Sustained-Release Weekly Amiloride Patch for the Management of Resistant Hypertension
Abstract
Resistant hypertension is a condition in which, despite simultaneous use of three classes of antihypertensive agents at their maximum doses, the blood pressure remains above the normal or ideal value of 120/80 mmHg. Amiloride, a potassium-sparing diuretic agent, has been found to be an option for add-on therapy. It is especially useful for diabetic patients who may be resistant to spironolactone, a drug in the same class as amiloride. When taken orally, the bioavailability of amiloride is 30-50%. Because adherence is a common issue for patients being treated with multiple agents for treatment-resistant hypertension, oral administration of amiloride may provide little to no added benefit for this patient population. In addition, bothersome gastrointestinal side effects have been reported when administered orally. Considering these factors, our goal is to design a long-acting skin patch of amiloride. Preliminary studies showed oleyl alcohol and propylene glycol facilitated the skin permeation of amiloride (2% w/w) solution over 7 days. Therefore, suspension-type, acrylate (DURO-TAK 387-2516) and silicone (BIO-PSATM 7-4301)-based adhesive patches incorporating oleyl alcohol and propylene glycol were formulated with 2% amiloride. The formulation process involved optimization of the release liners and backing membranes. 3M™ Scotchpak™ 1022 and CoTran™ 9702 were determined to be the favorable ones, respectively. The patches were punched and coat weights were determined to be 31.60 ± 0.36 mg/cm2 (acrylate) and 51.83 ± 4.01 mg/cm2 (silicone). The skin patches were tested for drug permeation across dermatomed pig ear skin using Franz Diffusion Cells for 7 days. The drug permeation from the acrylate and silicone patches was found to be 5.48 ± 1.47 µg/cm2 and 9.77 ± 1.41 µg/cm2, respectively (p>0.05) after 7 days. Future studies will focus on enhancing drug concentration in the patches to further optimize the drug permeation to attain therapeutically relevant systemic concentrations of the drug.
Start Time
16-4-2025 9:00 AM
End Time
16-4-2025 11:30 AM
Presentation Type
Poster
Presentation Category
Health
Student Type
Clinical Doctoral Student (e.g., medical student, pharmacy student)
Faculty Mentor
Ashana Puri
Faculty Department
Pharmaceutical Sciences
Development of a Sustained-Release Weekly Amiloride Patch for the Management of Resistant Hypertension
Resistant hypertension is a condition in which, despite simultaneous use of three classes of antihypertensive agents at their maximum doses, the blood pressure remains above the normal or ideal value of 120/80 mmHg. Amiloride, a potassium-sparing diuretic agent, has been found to be an option for add-on therapy. It is especially useful for diabetic patients who may be resistant to spironolactone, a drug in the same class as amiloride. When taken orally, the bioavailability of amiloride is 30-50%. Because adherence is a common issue for patients being treated with multiple agents for treatment-resistant hypertension, oral administration of amiloride may provide little to no added benefit for this patient population. In addition, bothersome gastrointestinal side effects have been reported when administered orally. Considering these factors, our goal is to design a long-acting skin patch of amiloride. Preliminary studies showed oleyl alcohol and propylene glycol facilitated the skin permeation of amiloride (2% w/w) solution over 7 days. Therefore, suspension-type, acrylate (DURO-TAK 387-2516) and silicone (BIO-PSATM 7-4301)-based adhesive patches incorporating oleyl alcohol and propylene glycol were formulated with 2% amiloride. The formulation process involved optimization of the release liners and backing membranes. 3M™ Scotchpak™ 1022 and CoTran™ 9702 were determined to be the favorable ones, respectively. The patches were punched and coat weights were determined to be 31.60 ± 0.36 mg/cm2 (acrylate) and 51.83 ± 4.01 mg/cm2 (silicone). The skin patches were tested for drug permeation across dermatomed pig ear skin using Franz Diffusion Cells for 7 days. The drug permeation from the acrylate and silicone patches was found to be 5.48 ± 1.47 µg/cm2 and 9.77 ± 1.41 µg/cm2, respectively (p>0.05) after 7 days. Future studies will focus on enhancing drug concentration in the patches to further optimize the drug permeation to attain therapeutically relevant systemic concentrations of the drug.