Evaluation of the Effect of Combining a Penetration Enhancer to a pH Modifier on Enhancing the Sublingual Permeability of Atropine sulfate from Fast Disintegrating Sublingual Tablets

Nova Southeastern University, Davie, Florida, USA

Objective: To evaluate the effect of combining different permeability enhancers to a pH modifier incorporated into fast disintegrating sublingual tablets (FDSTs) on the sublingual permeability of atropine sulfate (AS). Method: Five FDSTs formulations of AS 8 mg containing Na Bicarb 1%, as an alkalizing agent, and a transcellular (0.5% or 1% sodium dodecyl sulfate (SDS); or 15% or 20% sodium glycholate (Na Gly), or a paracellular (16% palmitoyl carnitine chloride (PCC)) enhancers, were manufactured. AS permeability was evaluated through an excised porcine sublingual membrane. AS FDSTs with no pH modifier and penetration enhancer were used as controls. Samples were then analyzed using HPLC-UV and the cumulative amount of AS was calculated and statistically compared using ANOVA and Tukey-Kramer Tests (p<0.05). Results: Mean (± SD) area under the curve (AUC0-90) of cumulative drug diffused with 0.5% SDS, 1% SDS, 15% Na Gly, 20% Na Gly, and 16% PCC were statistically higher than controls. The AUC0-90 of AS FDSTs with transcellular enhancers (SDS and Na Gly) were significantly higher than with paracellular enhancer (PCC). Also, AS influx and permeability from AS FDSTs with transcellular enhancers were significantly higher than with paracellular enhancer and controls. Incorporating SDS 1% with Na Bicarb 1% achieved the highest enhancement in AS sublingual permeability and increased AS permeability 17-fold compared to controls. Conclusion: The addition of penetration enhancers along with pH modifier into AS FDST formulation significantly enhanced AS sublingual permeability. Transcellular enhancers were superior to paracellular enhancer, which suggest a transcellular passive transport mechanism for AS.