Development of a Novel Aspirin Suppository Formulation and Evaluation of the Acetylation of COX-1 Via a HT-29/Caco-2 Cell Absorption Assay Used to Detect the Absorption of Aspirin Formulated With Various Bases and Excipients

Abstract

As the baby-boomer population ages, hospitalization rates will rise, increasing the number of patients who are NPO. Research indicates that aspirin use also increases with advanced age. With the increased prevalence of this demographic, there continues to be a growing need for alternative dosage forms for aspirin administration. A common and limited-risk alternative is rectally administered aspirin. However, there appears to be only one commercially available aspirin suppository and it has yielded erratic results as shown in previous research. Aspirin is considered a pro-drug; once it is inside the body, the acidic environment cleaves the aspirin molecule down to salicylic acid, its active form. Rectal cells may not provide an acidic environment needed to cleave the aspirin molecule into salicylic acid, thereby inhibiting the absorption and rate of onset of the drug. With this thought in mind and with the erratic results from the literature, the aim of this study, to be completed by summer of 2015, is to create a novel aspirin suppository. The study will be a prospective preclinical in-vitro design conducted in the Cedarville University Pharmaceutical Sciences lab. The samples will include two colonic adenocarcinoma cell lines, Caco-2 and HT-29. A standard curve will be developed as a baseline by using a 12(S)-HETE ELISA Assay using purified 12(S)-HETE. The two cell lines will be cultured, then incubated. Aspirin will be added to the samples and incubated again for 30 minutes. After incubation, medium samples will be taken and the same ELISA Assay will be performed on the results. The cell line that yields the most consistent results will be selected. The various aspirin formulations will be tested on this cell line in the same fashion. The ELISA assay will be performed and the concentration of 12(S)-HETE will be determined, plotted, and compared to the standard curve. A repeated-measures ANOVA will then be performed to analyze statistical significance