Preparation and Characterization of Ion-Sensitive Brimonidine Tartrate In Situ Gel for Ocular Delivery
Abstract
:1. Introduction
2. Materials and Methods
2.1. Chemicals
2.2. Animals
2.3. Formulation Screening
2.3.1. Formulation Preparation
2.3.2. Gelation Ability
2.3.3. Viscosity Measurement
2.4. In Vitro Release Study
2.5. Permeation Studies
2.5.1. Dialysis Membrane Permeation Study
2.5.2. Ex Vivo Transcorneal and Transscleral Permeation Studies
2.5.3. Mathematical Modeling of Drug Release Kinetics
2.6. Pre-Corneal Retention Study
2.7. Ocular Irritation Studies
2.8. Stability Studies of BRT-ISG
2.9. Study on the Pharmacokinetics of Ophthalmic BRT-ISG in Rabbit Anterior Chamber
3. Results and Discussion
3.1. Formulation Screening
3.1.1. Gelation Ability
3.1.2. Viscosity Measurement
3.2. In Vitro Release Study
3.3. Permeation Studies
3.3.1. Dialysis Membrane Permeation Study
3.3.2. Ex Vivo Transcorneal and Transscleral Permeation Studies
3.4. Pre-Corneal Retention Study
3.5. Ocular Irritation Studies
3.6. Stability Studies of BRT-ISG
3.7. Study on the Pharmacokinetics of Ophthalmic BRT-ISG in Rabbit Anterior Chamber
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Formulations | Gellan Gum/% | HPMC/% | Gelling Capacity |
---|---|---|---|
1 | 0.3 | + | |
2 | 0.4 | ++ | |
3 | 0.45 | ++ | |
4 | 0.45 | 0.1 | ++ |
5 | 0.45 | 0.2 | ++ |
6 | 0.5 | ++ | |
7 | 0.6 | ++ |
Methods | Zero-Order Equation | First-Order Equation | Higuchi Equation | Ritger–Peppas Equation | |
---|---|---|---|---|---|
R2 | R2 | R2 | R2 | n | |
Dialysis bag model | 0.548 | 0. 963 | 0.680 | 0.804 | 0.157 |
Dialysis membrane permeation model | 0.862 | 0.997 | 0.980 | 0.968 | 0.564 |
Transscleral permeation model | 0.932 | 0.984 | 0.978 | 0.963 | 0.754 |
Transcorneal permeation model | 0.978 | 0.985 | 0.992 | 0.980 | 0.950 |
Temperature /°C | Time /Day | Appearance Characters | pH | Osmolarity /mOsmol/kg | Contents /% | Impurity Contents/% |
---|---|---|---|---|---|---|
0 | light yellow, odorless and transparent | 6.74 ± 0.05 | 289.0 ± 1.0 | 99.96 ± 0.25 | Signal 0.0% All 0.0% | |
40 | 5 | light yellow, odorless and transparent | 6.72 ± 0.04 | 288.0 ± 2.6 | 100.51 ± 0.03 | |
10 | light yellow, odorless and transparent | 6.71 ± 0.03 | 292.0 ± 4.2 | 101.83 ± 0.52 | Signal 0.0% All 0.04% | |
60 | 5 | light yellow, odorless and transparent | 6.75 ± 0.03 | 296.0 ± 2.6 | 102.22 ± 0.05 | |
10 | light yellow, odorless and transparent | 6.79 ± 0.02 | 302.0 ± 4.0 | 100.67 ± 0.35 | Signal 0.0% All 0.02% | |
4500 lx ± 500 lx | 5 | light yellow, odorless and transparent | 6.73 ± 0.05 | 288.0 ± 1.5 | 99.40 ± 0.05 | |
10 | light yellow, odorless and transparent | 6.75 ± 0.03 | 292.0 ± 3.1 | 100.86 ± 0.22 | Signal 0.02% All 0.41% |
Temperature /°C | Time /Month | Appearance Characters | pH | Osmolarity /mOsmol/kg | Contents /% | Impurity Contents/% |
---|---|---|---|---|---|---|
0 | light yellow, odorless and transparent | 6.74 ± 0.05 | 289.0 ± 1.0 | 99.96 ± 0.25 | Signal 0.0% All 0.0% | |
40 | 1 | light yellow, odorless and transparent | 6.73 ± 0.02 | 296.0 ± 2.1 | 99.24 ± 0.86 | Signal 0.02% All 0.06% |
2 | light yellow, odorless and transparent | 6.75 ± 0.03 | 294.0 ± 1.5 | 99.11 ± 1.02 | Signal 0.05% All 0.14% | |
3 | light yellow, odorless and transparent | 6.79 ± 0.02 | 298.0 ± 2.5 | 100.46 ± 1.02 | Signal 0.06% All 0.15% | |
6 | light yellow, odorless and transparent | 6.85 ± 0.04 | 301.0 ± 2.9 | 100.55 ± 0.19 | Signal 0.14% All 0.33% |
Parameter | Eye Drops | BRT−ISG | |
---|---|---|---|
AUC(0-t) | mg·min/L | 412.61 ± 204.31 | 1397.08 ± 444.57 ** |
AUC(0-∞) | mg·min/L | 426.34 ± 212.54 | 1514.91 ± 504.58 ** |
MRT(0-t) | min | 110.28 ± 18.17 | 140.06 ± 17.50 ** |
MRT(0-∞) | min | 121.04 ± 20.02 | 165.31 ± 22.36 ** |
t1/2 | min | 64.99 ± 19.18 | 75.60 ± 17.66 |
Tmax | min | 60 ± 21.21 | 93.00 ± 28.98 ** |
Cmax | mg/L | 3.06 ± 1.42 | 8.16 ± 2.62 ** |
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Xu, H.; Liu, Y.; Jin, L.; Chen, X.; Chen, X.; Wang, Q.; Tang, Z. Preparation and Characterization of Ion-Sensitive Brimonidine Tartrate In Situ Gel for Ocular Delivery. Pharmaceuticals 2023, 16, 90. https://doi.org/10.3390/ph16010090
Xu H, Liu Y, Jin L, Chen X, Chen X, Wang Q, Tang Z. Preparation and Characterization of Ion-Sensitive Brimonidine Tartrate In Situ Gel for Ocular Delivery. Pharmaceuticals. 2023; 16(1):90. https://doi.org/10.3390/ph16010090
Chicago/Turabian StyleXu, Haonan, Ye Liu, Lu Jin, Xu Chen, Xinghao Chen, Qiao Wang, and Zhan Tang. 2023. "Preparation and Characterization of Ion-Sensitive Brimonidine Tartrate In Situ Gel for Ocular Delivery" Pharmaceuticals 16, no. 1: 90. https://doi.org/10.3390/ph16010090