Comparative Study of Donepezil-Loaded Formulations for the Treatment of Alzheimer’s Disease by Nasal Administration
Abstract
:1. Introduction
2. Results and Discussion
2.1. Solubility and Preparation of DPZ Gels
2.2. Physicochemical Characterization of DPZ-CGel, DPZ-PGel1 and DPZ-PGel2
2.3. Stability Studies
2.4. Cytotoxicity Results
2.5. In Vitro Release Studies
2.6. Ex vivo Permeation Studies
3. Conclusions
4. Materials and Methods
4.1. Materials
4.2. Solubility Studies
4.3. Preparation of Formulations
4.4. Physicochemical Characterization of DPZ-CGel, DPZ-PGel1 and DPZ-PGel2
4.4.1. pH Determination
4.4.2. Morphological Analysis
4.4.3. Gelation Temperature
4.4.4. Viscosity and Rheological Behavior
4.4.5. Swelling Test
4.5. Stability Assays
4.6. Cytotoxicity Assay
4.7. In Vitro Drug Release Study
4.8. Permeation Studies through Ex Vivo Nasal Mucosa
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Ingredients (% w/w) | DPZ-CGel | DPZ-PGel1 | DPZ-PGel2 |
---|---|---|---|
DPZ | 6.25 mg/mL | 6.25 mg/mL | 6.25 mg/mL |
Chitosan | 1 | - | - |
Pluronic F-127 | - | 18 | 18 |
Transcutol® P | 20 | 20 | - |
N-Methylpyrrolidone | - | - | 5 |
Water | 59 | 62 | 77 |
Acid acetic solution | 20 | - | - |
Formulas | 25 °C | 35 °C | ||||||
---|---|---|---|---|---|---|---|---|
Viscosity (mPa·s) at 50 s−1 | Apparent Thixotropy (Pa/s) | Rheological Behavior | Mathematical Model | Viscosity (mPa.s) at 50 s−1 | Apparent Thixotropy (Pa/s) | Rheological Behavior | Mathematical Model | |
DPZ-CGEL | 487 ± 1.5 | 72.7 | Pseudoplastic | Cross (r = 1) | 335 ± 0.9 | 43.3 | Pseudoplastic | Cross (r = 1) |
DPZ-PGel1 | 336 ± 3.3 | 39.5 | Pseudoplastic | Cross (r = 1) | 1345 ± 16.6 | 441.4 | Pseudoplastic | Cross (r = 1) |
DPZ-PGel2 | 232 ± 0.9 | 15.3 | Pseudoplastic | Cross (r = 1) | 1112 ± 21.5 | 568.7 | Pseudoplastic | Cross (r = 1) |
Parameters | DPZ-CGel (Days) | DPZ-PGel1 (Days) | DPZ-PGel2 (Days) | |||
---|---|---|---|---|---|---|
1 | 30 | 1 | 30 | 1 | 30 | |
Appearance | Homogeneous and slightly yellowish | Homogeneous and slightly yellowish | Homogeneous and translucent | Homogeneous and translucent | Homogeneous and translucent | Homogeneous and translucent |
pH | 6.30 ± 0.09 | 6.18 ± 0.05 | 6.30 ± 0.09 | 6.22 ± 0.03 | 6.30 ± 0.09 | 6.39 ± 0.05 |
Drug content (%) | 99.70 ± 0.06 | 99.70 ± 0.09 | 99.60 ± 0.03 | 99.30 ± 0.08 | 101.30 ± 0.05 | 99.7 ± 0.10 |
Parameters | DPZ-CGel (Days) | DPZ-PGel1 (Days) | DPZ-PGel2 (Days) | |||
---|---|---|---|---|---|---|
1 | 30 | 1 | 30 | 1 | 30 | |
Appearance | Homogeneous and slightly yellowish | Homogeneous and slightly yellowish | Homogeneous and translucent | Homogeneous and translucent | Homogeneous and translucent | Homogeneous and translucent |
pH | 6.30 ± 0.09 | 6.33 ± 0.03 | 6.30 ± 0.09 | 6.26 ± 0.08 | 6.30 ± 0.09 | 6.39 ± 0.07 |
Drug content (%) | 99.70 ± 0.06 | 98.67 ± 0.05 | 99.60 ± 0.03 | 99.50 ± 0.06 | 101.30 ± 0.05 | 100.50 ± 0.15 |
Permeation Parameters | DPZ-CGel | DPZ-PGel1 | DPZ-PGel2 |
---|---|---|---|
Jss (µg/(h/cm2)) | 0.83 ± 0.07 b,c | 8.76 ± 0.92 a,c | 3.54 ± 0.29 |
Tl (h) | 0.45 ± 0.05 b,c | 0.34 ± 0.02 | 0.31 ± 0.03 |
P2 (1/h) | 0.37 ± 0.04 b,c | 0.48 ± 0.05 | 0.54 ± 0.05 |
P1 (cm) x 103 | 0.36 ± 0.04 b,c | 2.90 ± 0.35 a,c | 1.05 ± 0.18 |
Kp (cm/h) x 103 | 0.13 ± 0.01 b,c | 1.40 ± 0.20 a,c | 0.57 ± 0.07 |
Css (µg/mL) | 0.01 ± 0.00 b,c | 0.13 ± 0.02 a,c | 0.05 ± 0.00 |
Qret (µg drug/g tissue/cm2) | 546.96 ± 53.81 b,c | 620.23 ± 59.34 | 518.74 ± 57.21 |
Model | Equation |
---|---|
Newton | |
Bingham | |
Ostwald-de-Waele | |
Herschel-Bulkley | |
Casson | |
Cross |
Kinetic Model | Equation |
---|---|
Zero Order | |
Higuchi | |
First Order | |
Korsmeyer-Peppas |
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Espinoza, L.C.; Guaya, D.; Calpena, A.C.; Perotti, R.M.; Halbaut, L.; Sosa, L.; Brito-Llera, A.; Mallandrich, M. Comparative Study of Donepezil-Loaded Formulations for the Treatment of Alzheimer’s Disease by Nasal Administration. Gels 2022, 8, 715. https://doi.org/10.3390/gels8110715
Espinoza LC, Guaya D, Calpena AC, Perotti RM, Halbaut L, Sosa L, Brito-Llera A, Mallandrich M. Comparative Study of Donepezil-Loaded Formulations for the Treatment of Alzheimer’s Disease by Nasal Administration. Gels. 2022; 8(11):715. https://doi.org/10.3390/gels8110715
Chicago/Turabian StyleEspinoza, Lupe Carolina, Diana Guaya, Ana Cristina Calpena, Rodolfo Miguel Perotti, Lyda Halbaut, Lilian Sosa, Adriel Brito-Llera, and Mireia Mallandrich. 2022. "Comparative Study of Donepezil-Loaded Formulations for the Treatment of Alzheimer’s Disease by Nasal Administration" Gels 8, no. 11: 715. https://doi.org/10.3390/gels8110715