Investigating the Effect of Salcaprozate Sodium on Skin Permeation of Cromolyn Sodium
Location
Culp Ballroom
Start Date
4-7-2022 9:00 AM
End Date
4-7-2022 12:00 PM
Poster Number
89
Faculty Sponsor’s Department
Pharmaceutical Sciences
Name of Project's Faculty Sponsor
Ashana Puri
Additional Sponsors
Brooke Schmeichel, Thomas Jones
Competition Type
Competitive
Type
Poster Presentation
Project's Category
Public Health
Abstract or Artist's Statement
Drug delivery via skin is a non-invasive, patient compliant, and effective method for circulatory or skin-targeted therapeutic treatment. Based on its mechanism of action, a topical system employing cromolyn sodium (CS) poses as a cheaper, safer alternative to current treatments for atopic dermatitis, an allergic skin disease. Clinical studies have successfully treated atopic dermatitis with CS emulsions; however, semisolid CS gels have not been investigated and no commercial formula is available to date. Additionally, clinical doses of CS do not passively permeate skin, although different chemical enhancers can be incorporated into formulation to enhance cutaneous drug absorption. This study aimed to investigate salcaprozate sodium (SNAC) as a chemical enhancer for optimized drug delivery to the dermis for potential remedial effects of CS gels. Gels were prepared weight-to-weight by combining 4% CS, 1% hydroxypropyl cellulose as gelling agent, and respective amounts of propylene glycol as base. For SNAC gels, contents included 2.5%, 4.5%, and 9% SNAC, and amount of propylene glycol was adjusted accordingly. CS gel (4%) containing no SNAC was used as a control. After overnight shaking, gels were sonicated for 30 min to use in in vitro permeation studies. Porcine ear skin was mounted on Franz diffusion cells maintained at 37°C, and permeation studies were performed over 24 h for each formulated gel to determine their effect on CS permeation across skin. Donor compartment contained 100 μL gel while the receptor held phosphate buffered saline (PBS). At predetermined timepoints, 300 μL of receptor solution was sampled, replaced with fresh PBS, and analyzed using HPLC with CS detection at 236 nm. Following 24 h, remaining gel was removed, and skin surface was cleaned. Skin layers were manually separated, minced, and left to shake for 4 h to extract permeated drug using methanol. These samples were vacuum dried overnight and reconstituted with PBS to be analyzed using HPLC. Efficiency of skin extraction methods was evaluated by assessing amount of drug recovered from skin compared to amount of drug absorbed where results were plotted, and subsequent equations were used to correct skin data. Student’s T test with Welch’s correction was applied to confirm statistical significance between gels. Passive delivery of the 4% CS control gel to the dermis was 0 μg/cm2. The SNAC containing gels demonstrated significantly improved drug delivery to the dermis when compared to control for 2.5% (36.26 ± 13.05, p=0.05), 4.5% (11.64 ± 1.45, p=0.001), and 9% (35.87 ± 2.23, p=0.004) SNAC groups. No significant differences were observed between any SNAC gel group and the control gel regarding drug delivered to the epidermis or receptor over 24 h. This study observed the greatest delivery of CS to the dermis with the 2.5% SNAC gel, posing as a promising option for a commercially available topical CS gel for the skin-targeted treatment of atopic dermatitis.
Investigating the Effect of Salcaprozate Sodium on Skin Permeation of Cromolyn Sodium
Culp Ballroom
Drug delivery via skin is a non-invasive, patient compliant, and effective method for circulatory or skin-targeted therapeutic treatment. Based on its mechanism of action, a topical system employing cromolyn sodium (CS) poses as a cheaper, safer alternative to current treatments for atopic dermatitis, an allergic skin disease. Clinical studies have successfully treated atopic dermatitis with CS emulsions; however, semisolid CS gels have not been investigated and no commercial formula is available to date. Additionally, clinical doses of CS do not passively permeate skin, although different chemical enhancers can be incorporated into formulation to enhance cutaneous drug absorption. This study aimed to investigate salcaprozate sodium (SNAC) as a chemical enhancer for optimized drug delivery to the dermis for potential remedial effects of CS gels. Gels were prepared weight-to-weight by combining 4% CS, 1% hydroxypropyl cellulose as gelling agent, and respective amounts of propylene glycol as base. For SNAC gels, contents included 2.5%, 4.5%, and 9% SNAC, and amount of propylene glycol was adjusted accordingly. CS gel (4%) containing no SNAC was used as a control. After overnight shaking, gels were sonicated for 30 min to use in in vitro permeation studies. Porcine ear skin was mounted on Franz diffusion cells maintained at 37°C, and permeation studies were performed over 24 h for each formulated gel to determine their effect on CS permeation across skin. Donor compartment contained 100 μL gel while the receptor held phosphate buffered saline (PBS). At predetermined timepoints, 300 μL of receptor solution was sampled, replaced with fresh PBS, and analyzed using HPLC with CS detection at 236 nm. Following 24 h, remaining gel was removed, and skin surface was cleaned. Skin layers were manually separated, minced, and left to shake for 4 h to extract permeated drug using methanol. These samples were vacuum dried overnight and reconstituted with PBS to be analyzed using HPLC. Efficiency of skin extraction methods was evaluated by assessing amount of drug recovered from skin compared to amount of drug absorbed where results were plotted, and subsequent equations were used to correct skin data. Student’s T test with Welch’s correction was applied to confirm statistical significance between gels. Passive delivery of the 4% CS control gel to the dermis was 0 μg/cm2. The SNAC containing gels demonstrated significantly improved drug delivery to the dermis when compared to control for 2.5% (36.26 ± 13.05, p=0.05), 4.5% (11.64 ± 1.45, p=0.001), and 9% (35.87 ± 2.23, p=0.004) SNAC groups. No significant differences were observed between any SNAC gel group and the control gel regarding drug delivered to the epidermis or receptor over 24 h. This study observed the greatest delivery of CS to the dermis with the 2.5% SNAC gel, posing as a promising option for a commercially available topical CS gel for the skin-targeted treatment of atopic dermatitis.