NIOSOME-ENCAPSULATED CLOMIPRAMINE FOR TRANSDERMAL CONTROLLED DELIVERY
Clomipramine (CLM) is a highly selective inhibitor of serotonin reuptake antidepressant. The objective of the present research was to decrease the extensive first-pass metabolism of the drug in the liver by developing and optimizing niosomal transdermal formulation of CLM in order to improve its bioavailability. Niosomes were prepared according to Â Â Â Â Â 4 Ã— 22 factorial design where surfactant type was set at four levels (Tween 20, Tween 60, Span 20 and Span 60), surfactant to cholesterol ratio at two levels (1:1, and 1:0.5) and charge inducing agent (dicetyl phosphate) at two levels (present and absent). Entrapment efficiency (%EE) and release efficiency percentage after 6 h (RE6 %) were chosen as dependent variables. CLM loaded niosomes were prepared by employing a thin film hydration technique using different non-ionic surfactants (Tween 20, Tween 60, Span 20 or Span 60), in the presence of cholesterol and a negative charge inducer dicetyl phosphate (DP) in different molar ratios. The prepared niosomes were characterized for entrapment efficiency, shape, size, zeta-potential and in vitro drug release. The studies demonstrated successful preparation of CLM niosomes. Niosomes showed percentage entrapment efficiency (%EE) of 72.54 Â± 0.37 % for optimized formula (F5) which composed of (1:1:0.1 molar ratio of Tween 60, cholesterol and DP) and 25 mg of CLM. The selected formula F5 (1:1:0.1) was incorporated in gel base of HPMC-K15M (4%) and evaluated through in vitro release. Skin irritancy test performed on albino rats, showed no sign of irritation.
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