Development of a Cyclodextrin-Based Mucoadhesive-Thermosensitive In Situ Gel for Clonazepam Intranasal Delivery
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. HPLC Assay of Clonazepam (CLZ)
2.3. Experimental Design
2.4. Thermosensitive Gels Preparation
2.5. Characterization of Thermosensitive Gels
2.5.1. Determination of pH
2.5.2. Determination of Gelation Temperature
2.5.3. Determination of Gelation Time
2.5.4. Determination of Gel Strength
2.5.5. Determination of Gel Mucoadhesive Strength
2.5.6. Determination of Mucoadhesion Time
2.5.7. Rheological Studies
2.6. In Vitro Drug Release Studies
2.7. Cytotoxicity and Transport Studies
2.8. Statistical Analysis
3. Results
3.1. Pre-Formulation Studies with Design of Experiment (DoE)
3.2. Preparation and Characterization of Drug-Loaded Gel Formulations
3.3. In Vitro Drug Release Studies
3.4. Cytotoxicity and Transport Studies through Caco-2 Cells
3.5. Transport Experiments with Caco-2 Cells
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Conflicts of Interest
References
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Exp. No | PLX % w/v | HA % w/v | RAMEB % w/v | Chito Gl % w/v | Gel. T °C | Gel Time s | pH |
---|---|---|---|---|---|---|---|
1 | 20 | 0 | 3 | 0.1 | 32.0 | 72 | 5.68 |
2 | 24 | 0 | 3 | 0.1 | 28.0 | 43 | 5.53 |
3 | 20 | 0 | 5 | 0.1 | 31.0 | 97 | 5.29 |
4 | 24 | 0 | 5 | 0.1 | 29.0 | 55 | 5.22 |
5 | 20 | 0.50 | 3 | 0.1 | 32.0 | 55 | 6.35 |
6 | 24 | 0.50 | 3 | 0.1 | 28.0 | 30 | 6.43 |
7 | 20 | 0.50 | 5 | 0.1 | 31.0 | 60 | 6.43 |
8 | 24 | 0.50 | 5 | 0.1 | 29.0 | 31 | 6.53 |
9 | 22 | 0.25 | 4 | 0.1 | 30.0 | 74 | 6.24 |
10 | 22 | 0.25 | 4 | 0.1 | 29.5 | 73 | 6.10 |
11 | 22 | 0.25 | 4 | 0.1 | 29.5 | 77 | 6.30 |
Batch Code | PLX (% w/v) | HA (% w/v) | Chito Gl (% w/v) | RAMEB (% w/v) | CLZ (% w/v) |
---|---|---|---|---|---|
G1 | 22 | 0.25 | 0.1 | 3 | 0.060 |
G2 | 22 | 0.25 | 0.1 | 3 | / |
G3 | 22 | 0.25 | 0.1 | 4 | 0.080 |
G4 | 22 | 0.25 | 0.1 | 4 | / |
G5 | 22 | 0.25 | 0.1 | 5 | 0.095 |
G6 | 22 | 0.25 | 0.1 | 5 | / |
G0 | 22 | / | / | / | / |
G0A | 22 | 0.25 | / | / | / |
G0B | 22 | / | 0.1 | / | / |
G0AB | 22 | 0.25 | 0.1 | / | / |
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Cirri, M.; Maestrelli, F.; Nerli, G.; Mennini, N.; D’Ambrosio, M.; Luceri, C.; Mura, P.A. Development of a Cyclodextrin-Based Mucoadhesive-Thermosensitive In Situ Gel for Clonazepam Intranasal Delivery. Pharmaceutics 2021, 13, 969. https://doi.org/10.3390/pharmaceutics13070969
Cirri M, Maestrelli F, Nerli G, Mennini N, D’Ambrosio M, Luceri C, Mura PA. Development of a Cyclodextrin-Based Mucoadhesive-Thermosensitive In Situ Gel for Clonazepam Intranasal Delivery. Pharmaceutics. 2021; 13(7):969. https://doi.org/10.3390/pharmaceutics13070969
Chicago/Turabian StyleCirri, Marzia, Francesca Maestrelli, Giulia Nerli, Natascia Mennini, Mario D’Ambrosio, Cristina Luceri, and Paola Angela Mura. 2021. "Development of a Cyclodextrin-Based Mucoadhesive-Thermosensitive In Situ Gel for Clonazepam Intranasal Delivery" Pharmaceutics 13, no. 7: 969. https://doi.org/10.3390/pharmaceutics13070969
APA StyleCirri, M., Maestrelli, F., Nerli, G., Mennini, N., D’Ambrosio, M., Luceri, C., & Mura, P. A. (2021). Development of a Cyclodextrin-Based Mucoadhesive-Thermosensitive In Situ Gel for Clonazepam Intranasal Delivery. Pharmaceutics, 13(7), 969. https://doi.org/10.3390/pharmaceutics13070969