الفهرس 
Pharmaceutical study on a central nervous system acting drug
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Abstract
Haloperidol is one of the widely used antipsychotic drugs. When orally administered, it suffers from low bioavailability due to hepatic 1st pass metabolism. This study aimed at developing Hal-loaded spanlastics and penetration enhancer-containing spanlastics (PECSs) to increase transdermal permeation of Hal with sustained release. At first, spanlastics were prepared using Span 60 and various edge activators according to a 31.41 factorial design. The independent variables were the type of edge activator (Tween 60, Tween 80 or Pluronic F68) and Span 60: edge activator ratio (9:1, 8:2, 6:4 or 5:5). Then, the best two formulae (F6 and F7) were modified by adding one of three penetration enhancers, namely labrasol, transcutol and tetraglycol at 1 % w/v concentration. Both spanlastics and PECS were successfully prepared using ethanol injection method showing reasonable values of percentage entrapment efficiency (EE %), particle size (PS), polydispersity index (PDI) and zeta potential (ZP). The statistical analysis of the ex-vivo permeation parameters showed that formula F1L - made of Span® 60 and Tween® 80 at the weight ratio of 4:1along with 1% w/v Labrasol® as penetration enhancer- was the best formula. F1L 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 F1L showed a maximum yield by mixing of 100 æl of diluted formula with 50 æl saline having 200 MBq of 99mTc and containing 13.6 mg of reducing agent (NaBH4) and volume completed to 300 æl by saline at pH 10 for 10 min as reaction time. The biodistribution study showed that the transdermal 99mTc-F1L hydrogel exhibited a more sustained release with pulsatile behavior in the blood with high brain levels than the oral 99mTc-F1L dispersion. So, transdermal F1L hydrogel may be considered as a promising sustained release formula for the maintenance therapy with Hal with reduced dose size and less frequent administration