Effect of hydrophilic substances on liberation of quinidine from starch—methylcellulose spheres

The spheres were prepared by the desolvation technique combined with gravitational sedimentation of droplets of methylcellulose gel suspensions with the addition of 25% quinidine adsorbate on the potato starch and 5% hydrophilic agents such as Span 80, Tween 60, glyceryl monostearate or PEG 2000 instilled into a desolvation liquid (saturated sodium acetate:paraffin liquid:heptane 1:1:1, v/v/v) through a standardized capillary.As follows from the physicochemical studies the sphericity (Sp) changed within the range 1.020–1.314, the porosity (P) was 19.1–66.5% and the loading efficiency was 35.10–67.07%. The release studies show that the dissolution efficiency after 60 min (DE₆₀) in acidic medium was 78.6% for quinidine and 52.6–63.4% for the spheres; in phosphate buffer pH 6.8 DE₆₀ was 32.4% for quinidine, but ranged within 16.3–26.0% for the spheres. The release of the drug from the spheres was fast and it was slightly difference (the loaded drug was released within 60 min) in acidic medium, while differentation of release in the phosphate buffer made it possible to evaluate the effect of hydrophilic additives on the dissolution rate.The general process of release can be described by the modified Higuchi equation $M_t^{*}=K_0·(\sqrt{t}-\sqrt{T_D})$ , which facilitates the analysis of the theoretical amount of the released substance $M_t^{*}$ depending on the zero-order dissolution rate constant K₀ and the dissolution lag time (T_D). Accordingly, spheres with sustained release can be most effectively produced by addition of PEG 2000. These spheres are characterized by Sp = 1.035, P = 60.2% and a loading efficiency of quinidine 67.07%. The release in acidic medium proceeds with K₀ = 3.857 mg·min^−0.5 and T_D = 6.21 min, in phosphate buffer K₀ was 1.293 rng·min^−0.5 and T_D = 7.14 min. These parameters were of less importance for the other formulations. The modified Higuchi equation gives information about the parameters of drug released.