Abstract
Haloperidol (Hal) is one of the widely used antipsychotic drugs. When orally administered, it suffers from low bioavailability due to hepatic first pass metabolism. This study aimed at developing Hal-loaded penetration enhancer-containing spanlastics (PECSs) to increase transdermal permeation of Hal with sustained release. PECSs were successfully prepared using ethanol injection method showing reasonable values of percentage entrapment efficiency, particle size, polydispersity index and zeta potential. The statistical analysis of the ex vivo permeation parameters led to the choice of F1L – made of Span® 60 and Tween® 80 at the weight ratio of 4:1 along with 1% w/v Labrasol® – as the selected formula (SF). SF was formulated into a hydrogel by using 2.5% w/v of HPMC K4M. The hydrogel exhibited good in vitro characteristics. Also, it retained its physical and chemical stability for one month in the refrigerator. The radiolabeling of SF showed a maximum yield by mixing of 100 µl of diluted formula with 50 µl saline having 200 MBq of 99mTc and containing 13.6 mg of reducing agent (NaBH4) and volume completed to 300 µl by saline at pH 10 for 10 min as reaction time. The biodistribution study showed that the transdermal 99mTc-SF hydrogel exhibited a more sustained release pattern and longer circulation duration with pulsatile behavior in the blood and higher brain levels than the oral 99mTc-SF dispersion. So, transdermal hydrogel of SF may be considered a promising sustained release formula for Hal maintenance therapy with reduced dose size and less frequent administration than oral formula.
Highlights
Haloperidol (Hal), the dopamine D2 receptor antagonist is a widely prescribed typical antipsychotic drug for the acute and maintenance therapy of schizophrenia, mania and other psychiatric disorders (Derendorf, 1995; Dold et al, 2015)
TweenVR 80 and surfactant permeation enhancers (LabrasolVR and TranscutolVR P) if present promote the elasticity of the vesicles creating systems with disrupted packing characteristics able to squeeze themselves through the pores of the skin (Trotta et al, 2002)
That may be due to the fact that both LabrasolVR and TranscutolVR P are surfactants (Manconi et al, 2011) and they are largely incorporated in the vesicle bilayer and increase the vesicles permeability having adverse effect on EE%, while TetraglycolVR is not essentially a surfactant and its incorporation in the bilayer structure is not to the same degree and most of it remain in the medium (Hao et al, 2002; Ahad et al, 2009)
Summary
Haloperidol (Hal), the dopamine D2 receptor antagonist is a widely prescribed typical antipsychotic drug for the acute and maintenance therapy of schizophrenia, mania and other psychiatric disorders (Derendorf, 1995; Dold et al, 2015). The transdermal route, may be of special interest as a suitable alternative because it's noninvasive and avoids the hepatic first-pass metabolism. Other advantages of this route include its ability to maintain the drug delivery for long periods of time leading to decreased dosing frequency and higher patient compliance. It can be used for patients who can't swallow tablets and capsules and those who try to crush tablets to facilitate swallowing which is not acceptable in case of controlled release tablets (Tanner & Marks, 2008)
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