Development and Pharmacokinetic Evaluation of Novasomes for the Trans-nasal Delivery of Fluvoxamine Using Arachidonic Acid-Carboxymethyl Chitosan Conjugate.

Autor: Gulshan S; Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Faisalabad 38000, Pakistan., Shah S; Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Faisalabad 38000, Pakistan., Shah PA; College of Pharmacy, University of the Punjab, Lahore 54000, Pakistan., Irfan M; Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Faisalabad 38000, Pakistan., Saadullah M; Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Faisalabad 38000, Pakistan., Abbas G; Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Faisalabad 38000, Pakistan., Hanif M; Department of Pharmaceutics, Faculty of Pharmacy, Bahauddin Zakariya University Multan, Multan 60800, Pakistan., Rasul A; Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Faisalabad 38000, Pakistan., Ahmad N; School of Chemical and Materials Engineering, National University of Science and Technology, Islamabad 24090, Pakistan., Mahmood A; Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Faisalabad 38000, Pakistan., Basheer E; Department of Pharmacognosy, Faculty of Pharmaceutical Sciences, Government College University, Faisalabad 38000, Pakistan., Habib MO; Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Faisalabad 38000, Pakistan., Alotaibi HF; Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah Bint AbdulRahman University, Riyadh 11671, Saudi Arabia., Obaidullah AJ; Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia., Alsabhan JF; Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia., Alwassil OL; Department of Pharmaceutical Sciences, College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, Riyadh 11481, Saudi Arabia.
Jazyk: angličtina
Zdroj: Pharmaceutics [Pharmaceutics] 2023 Aug 31; Vol. 15 (9). Date of Electronic Publication: 2023 Aug 31.
DOI: 10.3390/pharmaceutics15092259
Abstrakt: Depression is the major mental illness which causes along with loss of interest in daily life, a feeling of hopelessness, appetite or weight changes, anger and irritability. Due to the hepatic first-pass metabolism, the absolute bioavailability of fluvoxamine (FVM) after oral administration is about 50%. By avoiding the pre-systemic metabolism, nasal delivery would boost bioavailability of FVM. Additionally, the absorption is anticipated to occur more quickly than it would via the oral route because of the existence of microvilli and high vasculature. A nonionic surfactant, cholesterol and an arachidonic acid-carboxymethyl chitosan (AA-CMCS) conjugate were used to develop FVM-loaded novasomes. To investigate the effects of surfactant concentration, AA-CMCS conjugate concentration and stirring speed on the novasomes' characteristics, a Box-Behnken design was used. The dependent variables chosen were zeta potential, polydispersity index and particle size. The AA-CMCS conjugate was confirmed by 1 H-NMR and FTIR. Using Design Expert software (version 7; Stat-Ease Inc., Minneapolis, MN, USA), novasomes were further optimized. The chosen optimal formulation (NAC8) was made up of AA-CMCS conjugate, Span 60 and cholesterol. Particle size, zeta potential and PDI values for NAC8 formulation were 101 nm, -35 mV and 0.263, respectively. The NAC8 formulation's DSC and TGA analysis demonstrated that the medication had been uniformly and amorphously distributed throughout the novasomes. The NAC8 formulation showed 99% and 90% FVM release and permeation, respectively, and the novasome adherence time was 24 h. An improved antidepressant effect along with five-fold increase in bioavailability of FVM was observed after trans-nasal administration of NAC8 formulation compared to the reference commercially available Flumin ® tablets. FVM-loaded novasomes administered via the nasal route may therefore constitute an advancement in the management of depression.
Databáze: MEDLINE
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