Tadalafil Sublingual Tablets Preparation Process Formulation And Preliminary Pharmacokinetic Study In Beagle Dogs

Objective First aim is to develop the prescription and preparation technique of tadalafil sublingual tablets based on the study of raw materials and tadalafil tablet.Second aim is to obtain the pharmacokinetic parameters of tadalafil tablet and tadalafil sublingual tablet by pharmacokinetic test in beagle dogs.Third aim is to analyze whether tadalafil sublingual tablet could shorten the peak time and improve the bioavailability by comparing the pharmacokinetic parameters with tadalafil tablet.Methods The final prescription and preparation technique of tadalafil sublingual tablets were determined by the technique of solid dispersion.What's more,the wetting time,disintegration time and dissolution rate were used as prescription evaluation indexes.The reproducibility of the prescription process and the accuracy of content and dissolution detection method were verified by prescription amplification,Thus to preliminary draft the quality standards of tadalafil sublingual tablet.The pharmacokinetic parameters of tadalafil tablet and tadalafil sublingual tablet were analyzed by pharmacokinetic study in Beagle dogs,and the significance of this experimental study was then obtained.Results Tadalafil sublingual tablets were prepared by solid dispersion technology with the air preparation process to improve the prescription of tadalafil sublingual tablets were comprised of(5mg)excipients lactose(50 mg),croscarmellose sodium(20 mg),microcrystalline cellulose(16 mg),poloxamer two(5 mg),silica(3 mg)and magnesium stearate(1 mg).The preparation process(100 pieces)was carried out by dissolving tadalafil(500 mg)in 300 m L of methanol,adding lactose(5 g)and stirring the mixture at 80 °C for 1 hour.The cream was sieved through 200 mesh after dring at80 °C for 1 hour,and then mixed and compressed withcross-Sodiumcarboxymethylcellulose(2g),microcrystallinecellulose(1.6 g),poloxamer(500 mg),silica(300 mg),and the like.Magnesium stearate(100 mg)Amplification and stability experiment results showed a good reproducibility ogf prescription process and a good stability ofthe formulation.The AUC(0-52h)of tadalafil sublingual tablet(T1,T2)and tadalafil tablet(R)were(761.141±692.435)?(868.784±592.38)and(714.734±692.435),AUC(0-?h)were(823.44±293.34)?(941.96±721.2)?(741.41±722.88),Cmaxwere(90.1±20.37)?(86.49±28.4)?(76.12±30.54),Tmaxwere(1.563±0.177)h?(1.5)h and(1.875±0.443)h.ConclusionThe study results show that tadalafil sublingual tablet was prepared and the dissolution of tadalafil is improved by the use of solid dispersion technology,Analysis of AUC and Cmax showed that tadalafil sublingual tablets can significantly improve bioavailability and peak concentration,but Tmax analysis showed that tadalafil sublingual tablets did not significantly shorten the time to peak.