Development and characterization of floating microballoons for oral delivery of cinnarizine by a factorial design

Abstract

Cinnarizine (CN) is a pipperazine derivative with anti-histaminic activity and high affinity to H₁ receptors. The objective of this study was to produce floating microspheres (FM) of CN by diffusion solvent evaporation technique to increase drug solubility and hence its bioavailability. The effect of process variables such as: Eudragit type, stirring rate and time of stirring after addition of oily phase to the aqueous phase were evaluated on the yield, particle size, loading, release and floating behaviors of microspheres using a factorial design. Release of CN from microspheres was studied in pHs: 1.2 and 7.2 using paddle technique. The samples of dissolution test were analysed spectrophotometrically at 256.1 nm and 256.5 nm respectively. particle size of microspheres was studied using microscopic method and their floating behavior was studied in HCl (0.1 N, pH 1.2) medium with Tween 20 (0.5% w/v). Eight formulations were produced by changing 3 variables each at 2 levels: Eudragit S100 (Ps) or a combination of two Eudragits S100:RLPO (1:3) (P_SR), stirring rate of 200 (R₂) or 300 rpm (R₃) and stirring time after addition of oily phase to the aqueous phase 0 (T₀) or 1 hr (T₁). The average size of microspheres was 300 µm. The highest yield efficiency (94%) was seen in P_SRR₃T₀ formulation and the greatest loading percentage was 8.5% in P_SRR₂T₁ formulation. The microspheres containing just Eudragit S100, didn't show suitable releasing profile during 8 hours in pH 1.2 but those containing combination of Eudragit S100:RL released approximately whole amount of CN during 10 hours (8 hours in pH 1.2 and 2 hours in pH 7.2). The highest floating percentage up to 6 hours was 77.5% in P_SR₂T₁ formulation. The type of Eudragit used seems to play an important role in producing sustained release floating microspheres. P_SRR₃T₀ formulation containing both types of Eudragit S100:RL (1.3) that releases 99.1% of the drug after 10 hours and 65% floating after 6 hr seems suitable for oral sustained delivery of CN.

Key Words: :

• Cinnarizine
• floating microsphere
• Eudragit S100
• Eudragit RL
• diffusion solvent evaporation