Abstract
Abstract
Background/objective: Niosomes are a versatile vesicle delivery system for transporting drugs via different types of drug delivery systems. Paliperidone (PAL) is a hydrophobic drug with anti-schizophrenic activity. In this study, the central aim was to prepare a niosomal PAL-loaded dosage form for the treatment and enhancement of the therapeutic response to schizophrenia. Method: Different surfactants, including Span 65, Span 80, Span 60/Tween 80, Span 65/Tween 80, and Span 80/Tween 80, were combined with cholesterol at surfactant-to-cholesterol ratios of 1:3 and 1:4 to prepare niosomes using the thin-film hydration method. The formulations were characterized for several parameters using a series of evaluation techniques such as particle size, entrapment efficiency (EE%), zeta potential, drug content, and drug release over 24 hour, in vitro permeation over 8 hours, scanning electron microscopy, Fourier-transformed infrared spectroscopy, X-ray diffraction, FESEM, and atomic force microscopy. The selected formula, F23, was then incorporated into carbopol 934 in a ratio of 1.5% (w/v) to formulate a gel. The gel dosage form was evaluated for drug release and FTIR Furthermore, an in vivo pharmacokinetic evaluation was conducted on rats weighing 200 ±50g to compare the transdermal nanoniosomal gel against an oral free paliperidone solution.
Result: The optimized PAL niosome formulation (cholesterol: Span 60: Tween 80 at 1:2:2 ratio) showed a vesicle size, PDI, zeta potential, drug content and entrapment efficiency of 139.5± 5.6 nm, 0.2102±0.3 , -28.238 ± 2.1 mV, 96% ±3.5 and 85.6% ±0.14, respectively. Moreover, the release of F23 in 6 hours was 56.2%, which denoted a sustained release. The prepared PAL-loaded niosome (F23) improved the cumulative amount of drug permeated (260 ± 0.3 µg/cm²), and steady-state transdermal flux (127.4±0.2 µg/cm²/h), with a lag time of about (0.16 ± 0.02 h) when compared to pure PAL drug. In the in vivo evaluation, the transdermal nanoniosomal gel demonstrated superior pharmacokinetic profiles compared to the oral solution, achieving a higher peak concentration C_max: 3.69 ng/ml vs. 3.25 ng/ml, prolonged time to reach peak concentration T_max: 24 h vs. 12h, and significantly improved bioavailability as reflected by the increased extent of absorption AUC_0-72: 160.83 ng/h/ml vs. 119.84 ng/h/ml; AUC_0-∞:183.92 ng/h/ml vs.132.68 ng/h/ml.
Conclusion: Thus, incorporation of paliperidone into a niosomal vesicle gel was found to be an efficient vesicular carrier for a transdermal delivery system, providing sustained release and enhanced systemic bioavailability.
| Has the manuscript been published | not published |
|---|---|
| Intend to be published in the IJPS ? | NO |
