Location
D.P. Culp Center Room 304
Start Date
4-5-2024 3:30 PM
End Date
4-5-2024 4:30 PM
Name of Project's Faculty Sponsor
Ashana Puri
Faculty Sponsor's Department
Pharmaceutical Sciences
Competition Type
Competitive
Type
Oral Presentation
Presentation Category
Health
Abstract or Artist's Statement
Resistant hypertension is a condition in which blood pressure remains above the ideal value (120/80 mmHg), despite concurrent use of three antihypertensive agents of different classes taken at maximally tolerated doses. Amiloride has been clinically proven to manage resistant hypertension in patients with multiple treatment regimens including a diuretic. Currently, it is available as an oral tablet, which is administered once daily with an oral bioavailability of 50%, which gets reduced to 30% when administered with food. In addition, gastrointestinal side effects are also reported. Patient adherence to the multi-drug treatment regimen has been found to be low in patients with resistant hypertension and hence, administering amiloride in oral forms may not solve the problem, despite its proven pharmacological efficacy in such situations. Thus, considering the low oral bioavailability, associated side effects, and prospects of better patient compliance, our study aims to investigate the passive transdermal delivery of amiloride and evaluate the effects of chemical enhancement techniques on its permeation through dermatomed porcine ear skin into the dermis layer. Our long-term goal is to design a long-acting skin patch for transdermal delivery of amiloride for the management of resistant hypertension. Our hypothesis suggests the use of chemical enhancers will significantly enhance drug permeation across the skin. Chemical enhancers explored included oleic acid, oleyl alcohol, vitamin E TPGS, N-methyl-2-pyrrolidone (NMP), and a combination of oleic acid and oleyl alcohol. Drugs in propylene glycol served as the control. In vitro, permeation studies of the amiloride drug solution in different chemical enhancers were conducted across dermatomed porcine ear skin using Franz Diffusion Cells to determine 168-hour drug permeation profiles. Oleyl alcohol (761.86 ±74.97 µg/cm2) and oleic acid (691.90 ±78. 59 µg/cm2) significantly enhanced the permeation flux over 7 days as compared to the control in propylene glycol (193.42 ±38.02 µg/cm2) (p0.05). Our research findings have indicated a marked improvement in amiloride permeation through porcine skin using oleic acid and oleyl alcohol, providing valuable evidence to support our hypothesis. The encouraging results of this preliminary investigation provide evidence for the use of oleic acid and oleyl alcohol as chemical enhancers in transdermal preparations of amiloride to be used for the treatment regimen of resistant hypertension.
Effect of Chemical enhancers on Transdermal Delivery of Amiloride for Management of Resistant Hypertension
D.P. Culp Center Room 304
Resistant hypertension is a condition in which blood pressure remains above the ideal value (120/80 mmHg), despite concurrent use of three antihypertensive agents of different classes taken at maximally tolerated doses. Amiloride has been clinically proven to manage resistant hypertension in patients with multiple treatment regimens including a diuretic. Currently, it is available as an oral tablet, which is administered once daily with an oral bioavailability of 50%, which gets reduced to 30% when administered with food. In addition, gastrointestinal side effects are also reported. Patient adherence to the multi-drug treatment regimen has been found to be low in patients with resistant hypertension and hence, administering amiloride in oral forms may not solve the problem, despite its proven pharmacological efficacy in such situations. Thus, considering the low oral bioavailability, associated side effects, and prospects of better patient compliance, our study aims to investigate the passive transdermal delivery of amiloride and evaluate the effects of chemical enhancement techniques on its permeation through dermatomed porcine ear skin into the dermis layer. Our long-term goal is to design a long-acting skin patch for transdermal delivery of amiloride for the management of resistant hypertension. Our hypothesis suggests the use of chemical enhancers will significantly enhance drug permeation across the skin. Chemical enhancers explored included oleic acid, oleyl alcohol, vitamin E TPGS, N-methyl-2-pyrrolidone (NMP), and a combination of oleic acid and oleyl alcohol. Drugs in propylene glycol served as the control. In vitro, permeation studies of the amiloride drug solution in different chemical enhancers were conducted across dermatomed porcine ear skin using Franz Diffusion Cells to determine 168-hour drug permeation profiles. Oleyl alcohol (761.86 ±74.97 µg/cm2) and oleic acid (691.90 ±78. 59 µg/cm2) significantly enhanced the permeation flux over 7 days as compared to the control in propylene glycol (193.42 ±38.02 µg/cm2) (p0.05). Our research findings have indicated a marked improvement in amiloride permeation through porcine skin using oleic acid and oleyl alcohol, providing valuable evidence to support our hypothesis. The encouraging results of this preliminary investigation provide evidence for the use of oleic acid and oleyl alcohol as chemical enhancers in transdermal preparations of amiloride to be used for the treatment regimen of resistant hypertension.