Intranasal delivery of Clozapine using nanoemulsion-based in-situ gels: An approach for bioavailability enhancement

Abdulla, Nourhan A.; Balata, Gehan F.; Elghamry, Hanaa A.; Gomaa, Eman Zakaria

doi:10.1016/j.jsps.2021.11.006

Cited by 40 publications

(15 citation statements)

References 80 publications

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“…The zeta potential values of the binary mixed micelles were low at −2.7 ± 1.1 mV for PS20-P407 and −3.0 ± 0.8 mV for PS80-P407. The stability of the micelles could be attributed to the hydrophilic groups of P407 and polysorbates, which may have provided a protective barrier and promoted steric stabilization by retarding Ostwald ripening and coalescence [ 36 , 37 ]. Upon visual inspection and on centrifugation at 12,000 rpm for 30 min at 4 °C, the sol–gels exhibited no phase separation after each time point.…”

Section: Resultsmentioning

confidence: 99%

Clozapine-Encapsulated Binary Mixed Micelles in Thermosensitive Sol–Gels for Intranasal Administration

Tan

Pandey

Falconer

et al. 2022

Gels

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(1) Background: Clozapine is the most effective antipsychotic. It is, however, associated with many adverse drug reactions. Nose-to-brain (N2B) delivery offers a promising approach. This study aims to develop clozapine-encapsulated thermosensitive sol–gels for N2B delivery. (2) Methods: Poloxamer 407 and hydroxypropyl methylcellulose were mixed and hydrated with water. Glycerin and carbopol solutions were added to the mixture and stirred overnight at 2–8 °C. Clozapine 0.1% w/w was stirred with polysorbate 20 (PS20) or polysorbate 80 (PS80) at RT (25 °C) before being added to the polymer solution. The final formulation was made to 10 g with water, stirred overnight at 2–8 °C and then adjusted to pH 5.5. (3) Results: Formulations F3 (3% PS20) and F4 (3% PS80) were selected for further evaluation, as their gelation temperatures were near 28 °C. The hydrodynamic particle diameter of clozapine was 18.7 ± 0.2 nm in F3 and 20.0 ± 0.4 nm in F4. The results show a crystallinity change in clozapine to amorphous. Drug release studies showed a 59.1 ± 3.0% (F3) and 53.1 ± 2.7% (F4) clozapine release after 72 h. Clozapine permeated after 8 h was 20.8 ± 3.0% (F3) and 17.8 ± 3.1% (F4). The drug deposition was higher with F4 (144.8 ± 1.4 µg/g) than F3 (110.7 ± 2.7 µg/g). Both sol–gels showed no phase separation after 3 months. (4) Conclusions: Binary PS80-P407 mixed micelles were more thermodynamically stable and rigid due to the higher synergism of both surfactants. However, binary mixed PS20-P407 micelles showed better drug permeation across the nasal mucosa tissue and may be a preferable carrier system for the intranasal administration of clozapine.

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Section: Resultsmentioning

confidence: 99%

Clozapine-Encapsulated Binary Mixed Micelles in Thermosensitive Sol–Gels for Intranasal Administration

Tan

Pandey

Falconer

et al. 2022

Gels

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“…The developed nanoemulsion was then converted into an in situ gel by using Pluronic® F-127 (PF127) and F-68 (PF68). Ciliotoxicity examinations also showed no damage to the epithelium lining and cells of the nasal mucosa after application of the formulation ( Abdulla et al, 2021 ).…”

Section: Recent Advancement Of Delivering Antipsychotics Using Intran...mentioning

confidence: 99%

Advances and Challenges in Intranasal Delivery of Antipsychotic Agents Targeting the Central Nervous System

et al. 2022

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Treatment of central nervous system (CNS) disorders is challenging using conventional delivery strategies and routes of administration because of the presence of the blood–brain barrier (BBB). This BBB restricts the permeation of most of the therapeutics targeting the brain because of its impervious characteristics. Thus, the challenges of delivering the therapeutic agents across the BBB to the brain overcoming the issue of insufficient entry of neurotherapeutics require immediate attention for recovering from the issues by the use of modern platforms of drug delivery and novel routes of administration. Therefore, the advancement of drug delivery tools and delivering these tools using the intranasal route of drug administration have shown the potential of circumventing the BBB, thereby delivering the therapeutics to the brain at a significant concentration with minimal exposure to systemic circulation. These novel strategies could lead to improved efficacy of antipsychotic agents using several advanced drug delivery tools while delivered via the intranasal route. This review emphasized the present challenges of delivering the neurotherapeutics to the brain using conventional routes of administration and overcoming the issues by exploring the intranasal route of drug administration to deliver the therapeutics circumventing the biological barrier of the brain. An overview of different problems with corresponding solutions in administering therapeutics via the intranasal route with special emphasis on advanced drug delivery systems targeting to deliver CNS therapeutics has been focused. Furthermore, preclinical and clinical advancements on the delivery of antipsychotics using this intranasal route have also been emphasized.

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“…Abdulla et al [ 237 ] developed a nanoemulsion-based in-situ gel, also called emulgel, of clozapine for intranasal administration as an approach for bioavailability enhancement. Clozapine is an antipsychotic agent used in the treatment of schizophrenia [ 238 ].…”

Section: Applications Of Cross-linked Gels In Cns Drug Deliverymentioning

confidence: 99%

“…Clozapine is an antipsychotic agent used in the treatment of schizophrenia [ 238 ]. It displays limited solubility and is subject to hepatic first-pass metabolism when administered orally [ 237 , 238 ]. In this study, clozapine-loaded nanoemulsion was dispersed in an aqueous PF127 mobile phase.…”

Section: Applications Of Cross-linked Gels In Cns Drug Deliverymentioning

confidence: 99%

“…In this study, clozapine-loaded nanoemulsion was dispersed in an aqueous PF127 mobile phase. The optimized formulation demonstrated a high release profile, small average globule size (<100 nm), and low viscosity [ 237 ]. Particles with small sizes (<100 nm) are a critical factor for nose-to-brain drug delivery as they produce a larger surface area, enhancing the rate of drug absorption through olfactory and trigeminal nerve terminations [ 237 ].…”

Section: Applications Of Cross-linked Gels In Cns Drug Deliverymentioning

confidence: 99%

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A Comprehensive Review of Cross-Linked Gels as Vehicles for Drug Delivery to Treat Central Nervous System Disorders

Mashabela

Maboa

Miya

et al. 2022

Gels

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Gels are attractive candidates for drug delivery because they are easily producible while offering sustained and/or controlled drug release through various mechanisms by releasing the therapeutic agent at the site of action or absorption. Gels can be classified based on various characteristics including the nature of solvents used during preparation and the method of cross-linking. The development of novel gel systems for local or systemic drug delivery in a sustained, controlled, and targetable manner has been at the epitome of recent advances in drug delivery systems. Cross-linked gels can be modified by altering their polymer composition and content for pharmaceutical and biomedical applications. These modifications have resulted in the development of stimuli-responsive and functionalized dosage forms that offer many advantages for effective dosing of drugs for Central Nervous System (CNS) conditions. In this review, the literature concerning recent advances in cross-linked gels for drug delivery to the CNS are explored. Injectable and non-injectable formulations intended for the treatment of diseases of the CNS together with the impact of recent advances in cross-linked gels on studies involving CNS drug delivery are discussed.

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Intranasal delivery of Clozapine using nanoemulsion-based in-situ gels: An approach for bioavailability enhancement

Cited by 40 publications

References 80 publications

Clozapine-Encapsulated Binary Mixed Micelles in Thermosensitive Sol–Gels for Intranasal Administration

Clozapine-Encapsulated Binary Mixed Micelles in Thermosensitive Sol–Gels for Intranasal Administration

Advances and Challenges in Intranasal Delivery of Antipsychotic Agents Targeting the Central Nervous System

A Comprehensive Review of Cross-Linked Gels as Vehicles for Drug Delivery to Treat Central Nervous System Disorders

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