Clozapine-Encapsulated Binary Mixed Micelles in Thermosensitive Sol-Gels for Intranasal Administration
| Autor: | Madeleine S. A. Tan, Preeti Pandey, James R. Falconer, Dan J. Siskind, Alexandra Balmanno, Harendra S. Parekh |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
postural hypotension
Polymers and Plastics Science Bioengineering General. Including alchemy Article metabolic syndrome Biomaterials QD1-65 poloxamer gel polysorbates QD1-999 QD146-197 clozapine Organic Chemistry hypersalivation constipation antipsychotic schizophrenia Chemistry nose-to-brain delivery hydrogel cardiomyopathy Inorganic chemistry |
| Zdroj: | Gels Gels, Vol 8, Iss 38, p 38 (2022) Gels; Volume 8; Issue 1; Pages: 38 |
| ISSN: | 2310-2861 |
| Popis: | (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. |
| Databáze: | OpenAIRE |
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