Issue 33, 2024

A novel mucoadhesive paliperidone-nanoemulsion developed using the ultrasonication method in the treatment of schizophrenia

Abstract

Aim: To develop paliperidone mucoadhesive-nanoemulsion (PLP-NE) to enhance brain bioavailability. To evaluate comparative effects of PLP-NE and CS-PLP-NE in the treatment of schizophrenia, followed by a toxicity study of opt-NE. Material and methods: Oil: oleic acid, surfactant: Tween-80, and co-surfactant: Labrasol were chosen based on the solubility and maximum nanoemulsion area. The ultrasonication technique was applied with the aqueous micro titration method for the development of PLP-NE. The optimization of the method for the excellent PLP-NE was performed using a central composite design based on a five-factor and four-level. Oil (% v/v), Smix (v/v%), ultrasonication intensity in percentage, ultrasonication time in minutes, and temperature (°C) were optimized and used to the independent variables. Results: The parameters i.e., oil (5%), Smix (10%), ultrasonication time (5.0 min), ultrasonication intensity (25%), and temperature (38 °C) were optimized and used as independent and dependent variables for the development of novel PLP-NE. Based on experimental data, the dependent variables, i.e., globule size (53.90 ± 4.01 nm), % transmittance (92.56% ± 1.06%), PDI (0.218 ± 0.007), and zeta potential (−11.60 ± 0.031 mV), were determined. The smooth near about spherical shaped of PLP-NE globules with, refractive index i.e., 1.62 ± 0.021, viscosity: 39 ± 6 cp with the pH: 7.40 ± 0.089, and content of drug (97.98 ± 0.39%) for optimized-PLP-NE. The optimized PLP-NE with oleic acid, Tween-80, and Labrasol was used to improve brain bioavailability with good permeation via the intranasal route. CS-PLP-NE yielded good mucoadhesive property results compared to paliperidone-nanoemulsion, and PLP-S containing a 0.751 minutes retention time with their deuterated-IS (0.806 min) and m/z of 427.2/207.2 with IS (m/z: 431.2/211.2) for PLP and PLP-IS. A calibration curve was plotted with a linear range of 1–2000 ng mL−1 with inter- and intraday accuracy (97.03–99.31%) and precision (1.69–50.05%). The results of AUC(0–24) and Cmax for PLP were found to be highly significant (p < 0.001) as an improvement of brain bioavailability in rats via intranasal delivery of CS-PLP-NE. Furthermore, the locomotion test, social interaction, and forced swimming test (forced swimming, climbing, and immobility) of a mucoadhesive CS-PLP-NE (intranasally) provided highly significant results with the improvement of behavioral analysis when compared to the PLP-NE and PLP-S studies. Conclusion: CS-PLP-NE (i.n.) showed highly significant results, i.e., p < 0.001 for the improvement of bioavailability of the brain in the treatment of schizophrenia. Optimized-mucoadhesive-CS-based-PLP-NE is safe and shows no toxicity.

Graphical abstract: A novel mucoadhesive paliperidone-nanoemulsion developed using the ultrasonication method in the treatment of schizophrenia

Article information

Article type
Paper
Submitted
25 Jun 2024
Accepted
11 Jul 2024
First published
01 Aug 2024
This article is Open Access
Creative Commons BY-NC license

RSC Adv., 2024,14, 23952-23972

A novel mucoadhesive paliperidone-nanoemulsion developed using the ultrasonication method in the treatment of schizophrenia

N. Ahmad, K. Ansari, M. K. Alamoudi, A. Haque, Z. Ullah, M. S. Khalid and S. Ahmad, RSC Adv., 2024, 14, 23952 DOI: 10.1039/D4RA04624B

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