Abstract
Background: Bilastine is a second-generation antihistamine belonging to poorly soluble, highly permeable drug class. This resulted in low and variable oral bioavailability. Being antihistaminic, its combination with caffeine is possible. Accordingly, the aim was to research bilastine/caffeine solid dispersion on the dissolution rate and oral bioavailability of bilastine.
Methods: Ethanol-aided kneading of mixtures of bilastine and caffeine at molar ratios of 1:1 (C1), 1:2 (C2) and 1:3 (C3) was achieved. The kneading process continued till complete vaporization of ethanol and was repeated four times. During the last co-grinding step, an amount of Avicel equivalent to bilastine weight was added to obtain flowable mixtures. The resultant systems were characterized by FTIR, DSC, PXRD and in-vitro dissolution. The optimum formulation was assessed in-vivo for antihistaminic effect using Carrageenan induced paw edema.
Results: Instrumental analysis indicated molecular dispersion of bilastine in caffeine matrix or transformation into amorphous state. The different formulations exhibited enhanced dissolution parameters compared to native bilastine. Pure bilastine powder exhibited dissolution efficiency (%DE) of 54.24% with only 10.96% of bilastine dose was dissolved in first five minutes (Q5). Co grinding of bilastine and caffeine increased Q5 to 33.64%, 54.80% and 63.94 % for C1, C2 and C3, respectively. Besides, % DE values reached 74.80%, 83.22% and 78.88% for them, respectively. Augmented dissolution improved bilastine antihistaminic efficacy of C2 reflecting better bioavailability. This was manifested as significant reduction in the area under edema formation in case of C2 compared to drug suspension, untreated group, the physical mixture, and the physical mixture without bilastine (Avicel plus caffeine).
Conclusion: The study introduced bilastine-caffeine solid dispersion as simple tool to hasten bilastine dissolution and efficacy.