Chronomodulated drug delivery system of salbutamol sulphate for the treatment of nocturnal asthma

Abstract

A time dependent pulsed release system consisting of an effervescent core surrounded by consecutive layers of swelling and rupturable polymers was prepared and evaluated. The cores containing salbutamol sulphate as bioactive agent were prepared by direct compression method using different ratios of microcrystalline cellulose and effervescent agent and then coated sequentially with an inner swelling layer containing a hydrocolloid, hydroxypropylmethylcellulose E5 and an outer rupturable layer having Eudragit RL/RS (1:1). The effects of various processing and formulative parameters on the performance of system were studied. The rupture and dissolution tests were studied using the USP paddle method at 50 rpm in 0.1 N HCl and phosphate buffer pH 6.8. The lag time of the drug release decreased by increasing the inner swelling layer and increased by increasing the rupturing layer level. All the results obtained in the present study suggest that osmotic pumping effect was involved which eventually lead to the drug release.

Keywords: Nocturnal asthma; circadian rhythm; rupturing layer; salbutamol sulphate; swelling layer; time-dependent drug delivery system.

Fig. 1

Scanning electron micrograph of the tablet showing core tablet with different layers of polymers.

Fig. 2

In vitro dissolution behavior of developed pulsatile drug delivery system.

Fig. 3

Effect of inner swelling layer concentration on the lag time of the time-dependent release tablet. Inner swelling layer concentrations were, 30% w/w (–♦–), 20% w/w (–■–) and 10 % w/w (–▲–).

Fig. 4

Effect of outer coating on % water uptake and lag time of developed pulsed release tablet. Eudragit outer coating levels used were 4 mg/cm² (–♦–), 6 mg/cm² (–■–), 8 mg/cm² (–▲–) and 10 mg/cm² (–●–).

Fig. 5

Effect of sodium chloride and sodium bicarbonate on the lag time of the pulsed release tablet. With sodium chloride (–♦.–) and without (–■–). With sodium bicarbonate (–▲–) and with out (–■–).

Fig. 6

Effect of paddle rotation (rpm) of dissolution apparatus on the lag time and release profile of pulsed release tablet. Paddle rotation 50 rpm (–♦–) and 100 rpm (–■–).

Fig. 7

Effect of pH of dissolution medium on lag time of pulsed release system. pH 1.2 (–♦–), pH 5.5 (–■–), pH 6.8 (–▲–) and pH 7.2 (–■–).