Formulation and Optimization of Bisoprolol Fumarate Orally Fast Dissolving Film with Combination of HPMC E15 and Maltodextrin as Matrix Polymers

Abstrak

Bisoprolol fumarate is a drug belonging β blockers group, and specifically is selective β1 adrenergic receptor blocker, a class medicines used primarily in cardiovascular diseases. The drug has 9-12 hrs half life (t_1/2) and shows bioavailability of more than 80%¹. An orally fast dissolving film dosage form with drug in mouth are absorbed through buccal/oral mucosa in to systemic circulation avoiding first pass metabolism². The study aimed to made of orally fast dissolving film bisoprolol fumarate by solvent casting method with combination of HPMC E15 and maltodextrin as matrix. Factorial design 2³was applied to optimize the formula of orally fast dissolving film bisoprolol fumarate by varying level of polymer, it was HPMC E15 300 – 600 mg, maltodextrin 50 – 150 mg, and PEG400 50 – 90 mg. The optimum formula was determined by superimposed contour plot from various parameters: physical properties of orally fast dissolving film bisoprolol fumarate such as thickness, folding endurance, surface pH, in vitro disintegration, hidration study, and drug release for 300 second using Design Expert ® program. The study result showed that physical properties of 8 formulas such as organoleptic test were transparent, homogeny, and smooth in both of side; thickness 0.062 – 0.132 mm; weight variation 50.85 – 70.60 mg; folding endurance 987 – 2012; surface pH 6.69 – 6.99; disintegration (drop method) 18.33 – 20.76 sec; disintegration (petridish method) 27.63 – 30.41 sec; in vitro dissolution for 300 sec was 94.35 – 98.99%; and swelling index up to 30 second was 146.63 – 173.34%. Based on superimposed contour plot Design Expert® from factor response of folding endurance, surface pH, in vitro disintegration drop method, in vitro disintegration petridish method, swelling index, dan DE₃₀₀with a statistically significant finding requires a P-value of 0.05 were obtained optimum formulas for the area in the range of HPMC E15 509.88 mg; Maltodextrin 108.63 mg; and PEG400 50 mg with the value of desirability 0.519.

Key Words: bisoprolol fumarate, orally fast dissolving film, factorial design