Effect of Cetrimide and Ascorbic Acid on in Vitro Human Skin Permeation of Haloperidol.

Abstract

Haloperidol (HP) is given in the treatment of acute psychosis as well as in maintenance therapy to prevent the relapse of the psychosis.1) Long-acting formulations are more meaningful in the maintenance therapy since long-term daily oral dose of 3 to 10 mg of HP 2) may lead to noncompliance. HP decanoate oily injection, the only long acting formulation available at present, has some disadvantages namely; complex dosing schedule while converting from oral therapy to depot therapy, 3) pain at the site of injection, individual to individual variation in the liberation of active drug from the parent drug 4) and marked variations of HP plasma concentration.5) Because of these disadvantages, the development of alternative long-acting formulations could be beneficial.Drug delivery via skin offers many advantages such as sustained drug delivery, improved patient compliance, reduced side effects, elimination of first-pass effect, interruption or termination of treatment when necessary. 6) However, many drugs require some mechanism to enhance their penetration through the excellent skin barrier to achieve therapeutic plasma concentration. One common approach is using chemical enhancers, which act by increasing the solubility of the drug in stratum corneum (SC) or disrupting the lipid matrix of SC or interacting with the intracellular protein.7) HP, which was reported to penetrate only sub-therapeutically through the human skin in vitro, would require penetration enhancers. 8) In this study, cetrimide and ascorbic acid, effect of which were studied in our earlier work on the permeation of HP through the rat skin in vitro, 9) were used at various concentrations 0.1, 0.3 and 0.6% (w/v) on human skin and the mechanism of enhancement by cetrimide was probed with diffusion profile kinetics and Fourier transform infrared (FT-IR) spectroscopy. ExperimentalMaterials HP, droperidol, DL-lactic acid, L-ascorbic acid, antibiotic antimycotic solution (100ϫ) and sodium dihydrogen phosphate monohydrate were purchased from Sigma Chemical Company and cetrimide from Chempure Pte Ltd., Singapore. All other chemical reagents were of at least reagent grade and all materials were used as supplied.Analytical Method Drug concentrations were determined by reversed phase HPLC (C 18 column, Hewlett Packard Pte Ltd., Germany) at 254 nm. Mobile phase consisted of 0.05 M phosphate buffer (pH 3) and acetonitrile in the ratio of 50 : 50. Droperidol was used as an internal standard. Flow rate was 1.3 ml/min and injection volume was 100 ml. Retention times of the internal standard and drug were approximately 4 and 6.5 min. Mean peak area ratios of the drug and internal standard in 0.03% (v/v) lactic acid were linearly related to the drug concentrations for the samples containing 1 to 7 mg/ml (rϭ0.9999). Intraday and interday coefficient of variations for all concentrations varied from 1.29 to 11.64%. Solubility Studies Excess of HP was added to 0.03% (v/v) lactic acid containing antibacterial antimycotic solution (1 in 100 dilution) with and without enhanc...

Characterization of an Antimicrobial Extract from Elaeagnus angustifolia

“…Thus, decreased antimicrobial activity of Elaeagnus angustifolia by lysozyme may be related to break down of polyphenolic glycosides (flavonoids). Our study on inactivation of the Elaeagnus angustifolia extract by detergents like Tween 80, Tween 20, Triton X100 and toluene showed that inactivation occurs because these detergents can interact with both proteins and lipids and this interaction is irreversible (14). It is therefore, tempting to propose the presence of a lipid compound which had a potent antimicrobial activity.…”

Overcoming the Stratum Corneum: The Modulation of Skin Penetration

“…Ascorbic acid has been tested for its penetration enhancement properties using haloperidol as a model drug and amber glass Franz-type diffusion cells for the permeation studies. Ascorbic acid did not increase the permeation of the drug but increased the haloperidol solubility in the vehicle, which leads to a concentration-dependent increase in the haloperidol fl ux [90] . The primary capsaicinoid capsaicin was tested to compare its skin penetration-enhancing effects with those of Azone.…”

Thermotropic and Spectroscopic Behavior of Skin: Relationship with Percutaneous Permeation Enhancement

“…Further, cetrimide treatment decreased the absorbance of amide A and amide II bands, probably due to its interaction with keratin. However, no shift in amide I band at 1650 cm -1 was observed, indicating that it failed to produce any change in protein conformation [185].…”