SMGA gels for the skin permeation of haloperidol.
Small molecule gelling agent (SMGA) gels were developed using the gelator GP-1 in the solvents, namely, isostearyl alcohol (ISA) and propylene glycol (PG), to deliver haloperidol through the skin. The concentrations of the drug, haloperidol, the enhancer, farnesol and the gelator, GP-1 are 3 mg/ml, 5% (w/v) and 5% (w/v), respectively. The study employed a three-factor full factorial statistical design to investigate the influence of factor level changes on the permeability coefficient and permeation lag-time of haloperidol. Gels were prepared by raising temperature to 120 degrees C, followed by natural cooling under room temperature of 22+/-1 degrees C. The rheological properties of the gels were examined with a strain-controlled dynamic mechanical method. The in vitro permeation study was conducted with automated flow-through type cells. The gels successfully incorporated the drug and enhancer without losing their aesthetic properties. The in vitro human skin permeation study showed the permeation of the drug in ISA-based gels reached the pseudo steady state faster than PG-based gels and were less affected by gelator. PG-based gels delivered the drug at a faster rate with the incorporation of the enhancer. GP-1 did not influence the drug permeation rate but it increased permeation lag-time. The co-existence of gelator or enhancer increased the lag-time to a larger extent than when used separately. The novel SMGA gels are suitable for topical or transdermal delivery.
Department of Pharmacy, National University of Singapore, Republic of Singapore.
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Kang
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Liu
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Sawant
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Ho
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Chan
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Chan
D000279:Administration, Cutaneous; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D004339:Drug Compounding; D005204:Farnesol / Q000737:chemistry; D005233:Fatty Alcohols / Q000737:chemistry; D005260:Female; D005782:Gels; D005971:Glutamates / Q000737:chemistry*; D006220:Haloperidol / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D010539:Permeability / Q000187:drug effects; D019946:Propylene Glycol / Q000737:chemistry; D012212:Rheology; D012869:Skin Absorption
D014150:Antipsychotic Agents; D004337:Drug Carriers; D005233:Fatty Alcohols; D005782:Gels; D005971:Glutamates; C507105:N-lauroyl-L-glutamic acid di-n-butylamide; D005204:Farnesol; D019946:Propylene Glycol; D006220:Haloperidol; C026199:isostearyl alcohol