Formulation and Characterization of Carvedilol Leciplex for Glaucoma Treatment: In-Vitro, Ex-Vivo and In-Vivo Study
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Formulation of Carvedilol Leciplex
2.3. Evaluation of Carvedilol Leciplex
2.3.1. Determination of Entrapment Efficiency (EE)
2.3.2. Particle Size, Distribution and Zeta Potential
2.3.3. Morphology
2.4. Ex-Vivo Corneal Permeation Study
2.5. In-Vivo Evaluation of Carvedilol Leciplex
2.5.1. Pharmacokinetic Study
2.5.2. Pharmacodynamic Study
2.5.3. Histological Examination
2.6. Statistical Analysis of Data
3. Results and Discussion
3.1. In-Vitro Evaluation of Carvedilol Leciplex
3.1.1. Entrapment Efficiency
3.1.2. Particle Size, Distribution and Zeta Potential
3.1.3. Morphology
3.2. Ex-Vivo Corneal Permeation
3.3. In-Vivo Evaluation of Carvedilol Leciplex
3.3.1. Pharmacokinetic Study
3.3.2. Pharmacodynamic Study
3.3.3. Histological Examination
4. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Formulation Code | Composition | |||
---|---|---|---|---|
SPC | CTAB | DDAB | Carvedilol | |
mg/mL | mg/mL | mg/mL | mg/mL | |
F1 | 18.6 | 8.7 | - | 5 |
F2 | 18.6 | - | 11.1 | 5 |
F3 | 31 | 2.9 | - | 5 |
F4 | 31 | - | 3.7 | 5 |
F5 | 18.6 | - | - | 5 |
F6 | 31 | - | - | 5 |
Formulation Code | Characteristics | |||
---|---|---|---|---|
PS | PDI | ZP | EE | |
nm | mV | % | ||
F1 | 91.48 ± 1.8 | 0.18 | 34.5 ± 0.58 | 95.10 ± 1.0 |
F2 | 16.04 ± 1.2 | 0.16 | 53.9 ± 0.91 | 95.59 ± 0.83 |
F3 | 706 ± 0.98 | 0. 47 | 31.6 ± 0.46 | 96.00 ± 0.98 |
F4 | 523 ± 1.1 | 0.50 | 47.2 ± 0.72 | 96.93 ± 1.3 |
F5 | 1094 ± 2.3 | 0.40 | 2.82 ± 0.54 | 95.27 ± 0.69 |
F6 | 1867 ± 1.5 | 0.70 | 7.83 ± 0.63 | 95.90 ± 0.94 |
Formulae | Jss (µg/cm2/h) | Papp (µg/cm) | Q8 (µg/cm2) |
---|---|---|---|
F1 | 13.40 ± 0.36 | 0.0134 ± 0.060 | 85.80 ± 0.56 |
F2 | 115.74 ± 0.21 | 0.1157 ± 0.044 | 480.36 ± 0.58 |
F3 | 2.47 ± 0.17 | 0.00247 ± 0.023 | 27.10 ± 1.1 |
F4 | 92.49 ± 0.54 | 0.0924 ± 0.091 | 402.83 ± 0.97 |
F5 | 7.82 ± 0.29 | 0.0078 ± 0.023 | 35.53 ± 0.87 |
F6 | 4.15 ± 0.13 | 0.00415 ± 0.020 | 23.60 ± 0.80 |
Drug sol. | 35.15 ± 0.19 | 0.03515 ± 0.01 | 201.49 ± 0.50 |
Pharmacokinetic Parameters | Carvedilol Solution | Carvedilol Leciplex |
---|---|---|
T1/2 (h) | 4.48 ± 0.8 | 7.0 ± 0.67 |
tmax (h) | 1 ± 0.19 | 0.5 ± 0.0 |
Cmax (µg/mL) | 5.93 ± 0.42 | 7.53 ± 0.61 |
AUC (0–6) (µg h/ML) | 41.79 ± 2.8 | 74.47 ± 4.3 |
MRT (h) | 6.64 ± 0.50 | 10.30 ± 0.96 |
Time (h) | Mean IOP of GP1 (mmHg) | Mean IOP of GP2 (mmHg) |
---|---|---|
0 | 40.9 ± 1.2 | 41.4 ± 1.5 |
0.25 | 38.00 ± 3.8 | 30.9 ± 2.1 |
0.5 | 29.21 ± 3.1 | 22.6 ± 2.10 |
1 | 22.5 ± 2.0 | 21.6 ± 1.0 |
2 | 22.5 ± 2.0 | 20.9 ± 0.00 |
4 | 22.5 ± 2.0 | 20.6 ± 0.73 |
6 | 24.4 ± 2.0 | 21.83 ± 2.3 |
8 | 27.7 ± 2.2 | 22.23 ± 2.6 |
10 | 30.4 ± 2.7 | 22.23 ± 2.6 |
12 | 30.4 ± 2.7 | 22.23 ± 2.6 |
24 | 37.0 ± 3.0 | 23.91 ± 3.71 |
48 | 41.7 ± 2.3 | 33.23 ± 1.4 |
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Hassan, D.H.; Abdelmonem, R.; Abdellatif, M.M. Formulation and Characterization of Carvedilol Leciplex for Glaucoma Treatment: In-Vitro, Ex-Vivo and In-Vivo Study. Pharmaceutics 2018, 10, 197. https://doi.org/10.3390/pharmaceutics10040197
Hassan DH, Abdelmonem R, Abdellatif MM. Formulation and Characterization of Carvedilol Leciplex for Glaucoma Treatment: In-Vitro, Ex-Vivo and In-Vivo Study. Pharmaceutics. 2018; 10(4):197. https://doi.org/10.3390/pharmaceutics10040197
Chicago/Turabian StyleHassan, Doaa H., Rehab Abdelmonem, and Menna M. Abdellatif. 2018. "Formulation and Characterization of Carvedilol Leciplex for Glaucoma Treatment: In-Vitro, Ex-Vivo and In-Vivo Study" Pharmaceutics 10, no. 4: 197. https://doi.org/10.3390/pharmaceutics10040197
APA StyleHassan, D. H., Abdelmonem, R., & Abdellatif, M. M. (2018). Formulation and Characterization of Carvedilol Leciplex for Glaucoma Treatment: In-Vitro, Ex-Vivo and In-Vivo Study. Pharmaceutics, 10(4), 197. https://doi.org/10.3390/pharmaceutics10040197