Abstract
In this study, a first attempt has been made to deliver levosulpiride transdermally through a thiolated chitosan microneedle patch (TC-MNP). Levosulpiride is slowly and weakly absorbed from the gastrointestinal tract with an oral bioavailability of less than 25% and short half-life of about 6 h. In order to enhance its bioavailability, levosulpiride-loaded thiolated chitosan microneedle patches (LS-TC-MNPs) were fabricated. Firstly, thiolated chitosan was synthesized and characterized by nuclear magnetic resonance (1HNMR) spectroscopy, attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy, differential scanning calorimetry (DSC), and X-ray diffraction (XRD). Thiolated chitosan has been used in different drug delivery systems; herein, thiolated chitosan has been used for the transdermal delivery of LS. LS-TC-MNPs were fabricated from different concentrations of thiolated chitosan solution. Furthermore, the levosulpiride-loaded thiolated chitosan microneedle patch (LS-TC-MNP) was characterized by FTIR spectroscopic analysis, scanning electron microscopy (SEM) study, penetration ability, tensile strength, moisture content, patch thickness, and elongation test. LS-TC-MNP fabricated with 3% thiolated chitosan solution was found to have the best tensile strength, moisture content, patch thickness, elongation, drug-loading efficiency, and drug content. Thiolated chitosan is biodegradable, nontoxic and has good absorption and swelling in the skin. LS-TC-MNP-3 consists of 100 needles in 10 rows each with 10 needles. The length of each microneedle was 575 μm; they were pyramidal in shape, with sharp pointed ends and a base diameter of 200 µm. The microneedle patch (LS-TC-MNP-3) resulted in-vitro drug release of 65% up to 48 h, ex vivo permeation of 63.6%, with good skin biocompatibility and enhanced in-vivo pharmacokinetics (AUC = 986 µg/mL·h, Cmax = 24.5 µg/mL) as compared to oral LS dispersion (AUC = 3.2 µg/mL·h, Cmax = 0.5 µg/mL). Based on the above results, LS-TC-MNP-3 seems to be a promising strategy for enhancing the bioavailability of levosulpiride.
Highlights
Levosulpiride was successfully delivered through transdermal route by using LS-thiolated chitosan microneedle patch (TC-microneedle patch (MNP))-3
Chitosan was modified into thiolated chitosan (TC) by thioglycolic acid and ethyl-3-(3-dimethylamino propyl) carbodiimide hydrochloride (EDAC) coupling
Microneedle patches were fabricated by different concentrations of thiolated chitosan solution
Summary
It is the levo-enantiomer of racemic sulpiride. It has several pharmacological properties, including antipsychotic and antidepressant action and effective against ulcer [1]. Levosulpiride is a biopharmaceutical classification system (BCS) class IV drug; it has low water solubility and low permeability [5]. It is not readily metabolized, as 70–90% of the intravenous dose and 15–25% of oral dose are excreted unchanged in the urine [6]. The drug is useful in lower doses (75 mg orally) for the treatment of irritable colon syndrome and duodenal or gastric ulcer related to psychosomatic stress [7].
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