Study Of Dutasteride SMEDDS Oral Films Drug Delivery Systems

Dutasteride is a second-generation 5α-reductase inhibitors, It is researched and developmented by GSK, It is the only listed suppressing typeⅠand typeⅡ 5α-reductase drugs at present and treatment for moderate、severe benign prostatic hyperplasia. Its oral absorption is better, and could absorbed through the skin. Dutasteride belongs to the classⅡin the Biopharmaceutics Classification, It is a drug of high permeability, low solubility.The article preparation dutasteride for oral films on the basis of Dutasteride liquid self-microemulsions. not only to improve the solubility and dissolution rate of the active substance, but also has a positive meaning in increased bioavailability, and reflect the advantages of solid preparations while maintaining the inherent advantages of liquid self-microemulsions, expand the applications scope of self-microemulsion formulation.Objective:To prepare dutasteride self-microemulsions oral films, and evaluate it in vitro and vivo.Methods: Adopt Single-factor test screening prescription, orthogonal design optimization prescription; preparation dutasteride self-microemulsions oral films by solvent casting method; study its appearance、 thickness、disintegrate time、in vitro dissolution、drug loading per unit area and other indicators; content of dutasteride in oral film was determined by HPLC; TEM was used to observe dutasteride self-microemulsion oral film surface features; SEM was used to observe dutasteride self-microemulsion oral film morphology after its re-dissolved in water; Particle size was measured by Malvern laser particle size analyzer; Compare pharmacokinetics of Dutasteride self-microemulsions oral films and Dutasteride soft capsules(Avodart) in Beagle dogs.Result: Dutasteride self-microemulsions oral films is smooth 、 no bubbles; disintegrate time is(26±2)s; Malvern laser particle size analyzer measured the average particle size of dutasteride self- microemulsion oral film after its re-dissolved in water is 147.9nm; TEM show dutasteride self-microemulsion exist in the form of oil droplets; SEM show dutasteride self-microemulsion oral film exist emulsion droplets after re-dissolved in water; vitro dissolution can be the same with listed in the medium with surfactant, was significantly faster than the listed dutasteride soft gelatin capsules; The majoy pharmacokinetic parameters of the test preparation and reference preparations were as follows: AUC0-t(2783.8±757.0) and(2886.6±829.7) ng?ml-1?h, AUC0-∞(2883.1±864.6) and(2891.4±629.9)ng?ml-1?h, t1/2(45.8±10.4) and(42.2±14.9)h, tmax(3.8± 3.6) and(4.1 ± 1.2) h, Cmax(46.1±3.3) and(45.3±8.5) ng/ml.Conclusion: Dutasteride self-microemulsions oral films not only maintains the characteristics of the liquid self-microemulsions, but also to solve the weekness of traditional liquid formulations, Oral film preparation method is simple, low cost, can improve patient compliance, will be beneficial in men with moderate、severe BPH treatment.