Bioequivalence Analysis of Terazosin Hydrochloride Tablets Based on Parallel Artificial Membrane Permeability Analysis
Abstract
:1. Introduction
2. Results
2.1. In Vitro Dissolution Profiles of TH Tablets
2.2. MacroFlux Assay of TH Tablets
2.3. Permeability of API
2.4. Permeability of the Powder of TH Tablets
2.5. Bioequivalence Studies of TH Tablets in Dogs
3. Discussion
3.1. In Vitro Dissolution Experiment
3.2. In Vitro Permeability Experiment
4. Materials and Methods
4.1. Instruments
4.2. Agents
4.3. In Vitro Dissolution Study
4.3.1. Experiment Conditions of Dissolution
4.3.2. Chromatographic Conditions
4.3.3. Calculation of In Vitro Dissolution Data
4.4. MacroFlux Assay for Evaluating the Permeation of TH Tablets
4.5. µFlux Assay for Evaluating the Permeability of API
4.6. µFlux Assay for Evaluating the Influence of Excipient
4.7. Bioequivalence Studies in Dogs
4.7.1. Experimental Method
4.7.2. Chromatographic and Mass Spectrometry Conditions
4.8. Statistical Analysis
4.8.1. Comparison of In Vitro Dissolution Profiles
4.8.2. PAMPA Experiments
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Enterprise | FaSSIF | FeSSIF | ||
---|---|---|---|---|
Flux (µg·min−1·cm−2) | Total Permeated Amount (µg) | Flux (µg·min−1·cm−2) | Total Permeated Amount (µg) | |
Abbott Laboratories | 0.00801 ± 0.00016 | 5.82 ± 0.03 | 0.00165 ± 0.00018 | 1.31 ± 0.21 |
A | 0.00729 ± 0.00018 | 5.32 ± 0.23 | 0.00153 ± 0.00007 | 1.32 ± 0.06 |
B | 0.00696 ± 0.00033 | 5.20 ± 0.20 | 0.00148 ± 0.00009 | 1.07 ± 0.08 |
C | 0.00752 ± 0.00030 | 5.36 ± 0.15 | 0.00166 ± 0.00010 | 1.29 ± 0.09 |
D | 0.00782 ± 0.00033 | 5.56 ± 0.16 | 0.00166 ± 0.00020 | 1.39 ± 0.13 |
E | 0.00705 ± 0.00021 | 5.11 ± 0.22 | 0.00152 ± 0.00005 | 1.21 ± 0.04 |
F | 0.00786 ± 0.00030 | 5.77 ± 0.36 | 0.00149 ± 0.00008 | 1.24 ± 0.06 |
G | 0.00667 ± 0.00028 | 5.46 ± 0.47 | 0.00142 ± 0.00013 | 1.24 ± 0.17 |
Enterprise | FaSSIF | FeSSIF | ||
---|---|---|---|---|
Flux (µg·min−1·cm−2) | Total Permeated Amount (µg) | Flux (µg·min−1·cm−2) | Total Permeated Amount (µg) | |
A | 87.20–94.60% | 84.81–98.10% | 85.22–99.70% | 93.07–108.56% |
B | 79.83–93.76% | 83.46–95.14% | 80.07–98.96% | 71.25–92.24% |
C | 87.48–100.23% | 87.83–96.45% | 90.86–110.33% | 86.33–110.85% |
D | 90.61–104.56% | 91.00–100.07% | 79.53–121.15% | 89.22–123.69% |
E | 83.59–92.26% | 81.47–94.16% | 86.74–97.39% | 87.23–98.13% |
F | 91.82–104.37% | 88.81–109.42% | 82.12–98.17% | 87.40–103.00% |
G | 77.39–89.14% | 80.26–107.57% | 72.42–99.78% | 73.30–116.15% |
pH | Enterprise | Pe (10−6 cm·s−1) | p-Value (t-Test) |
---|---|---|---|
5.0 | I | 2.61 ± 0.264 | 0.032 * |
II | 3.41 ± 0.333 | ||
6.5 | I | 75.67 ± 2.487 | 0.234 |
II | 78.70 ± 2.807 | ||
7.4 | I | 82.54 ± 5.939 | 0.091 |
II | 100.69 ± 12.885 |
Condition | Enterprise | Pe (10−6 cm·s−1) | p-Value (t-Test) |
---|---|---|---|
FaSSIF | Abbott Laboratories | 35.42 ± 3.02 | - |
B | 33.85 ± 2.16 | 0.503 | |
G | 31.27 ± 1.99 | 0.117 | |
FeSSIF | Abbott Laboratories | 4.74 ± 0.32 | - |
B | 5.14 ± 0.39 | 0.239 | |
D | 5.20 ± 0.38 | 0.186 | |
G | 5.70 ± 0.72 | 0.104 |
Enterprise | AUC(0–t) (ng·mL−1·h−2) | AUC(0–∞) (ng·mL−1·h−2) | Cmax (ng·mL−1) | Tmax (h) | t1/2β (h) |
---|---|---|---|---|---|
Abbott Laboratories | 545.27 ± 70.76 | 558.18 ± 72.66 | 55.68 ± 10.80 | 1.58 ± 0.66 | 8.18 ± 0.86 |
B | 535.50 ± 77.18 | 554.83 ± 76.97 | 56.49 ± 9.65 | 1.17 ± 0.41 | 9.14 ± 1.76 |
Enterprise | Parameter | T | R | T/R (%) | 90% Confidence Interval |
---|---|---|---|---|---|
A | Cmax | 49.36 | 50.04 | 97.68 | 91.05~104.79% |
AUC0–t | 481.3771 | 484.7605 | 99.30 | 96.44~102.25% | |
AUC0–∞ | 493.9153 | 496.4887 | 99.48 | 96.66~102.39% | |
D | Cmax | 47.225 | 43.812 | 107.79 | 98.39~118.09% |
AUC0–t | 411.6 | 406.7 | 101.23 | 96.17~106.55% | |
AUC0–∞ | 424.7 | 419.9 | 101.14 | 96.16~106.38% |
Enterprise | Composition of the Tablets | Formulation |
---|---|---|
Abbott | Lactose, corn starch, magnesium stearate, talcum powder | Wet granulation |
A | Lactose, ethanol, magnesium stearate, MCC, pre-gelatinized starch | Wet granulation |
B | Lactose, magnesium stearate, MCC, CMS-Na | Wet granulation |
C | Lactose, corn starch, 10% corn starch pulp, magnesium stearate | Wet granulation |
D | Lactose, magnesium stearate, MCC, CMC, pre-gelatinized starch | Direct powder compression |
E | Lactose, magnesium stearate, L-HPC | Wet granulation |
F | Lactose, magnesium stearate, MCC, CMS-Na | Wet granulation |
G | Lactose, corn starch, magnesium stearate, MCC, PVP-K30 | Wet granulation |
Time (min) | Phase A (%) | Phase B (%) |
---|---|---|
0 | 80 | 20 |
1 | 80 | 20 |
1 | 10 | 90 |
4 | 10 | 90 |
4 | 80 | 20 |
5 | 80 | 20 |
Parameter | TH | Prazosin Hydrochloride |
---|---|---|
Scanning mode | Positive | Positive |
Ion source | ESI | ESI |
Spray voltage (V) | 3500 | 3500 |
Shealth gas (psi) | 35 | 35 |
Aux gas (psi) | 10 | 10 |
Capillary temperature (℃) | 400 | 400 |
Detection mode | SRM | SRM |
Precursor ion (m/z) | 388.083 | 384.027 |
Product ion (m/z) | 290.090 | 231.040 |
Tube lens (V) | 94 | 97 |
Collision energy (V) | 25 | 40 |
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Niu, J.; Huang, H.; Ji, M.; Zhang, W.; Huang, Y.; Ma, L.; Wang, B.; Liu, Q. Bioequivalence Analysis of Terazosin Hydrochloride Tablets Based on Parallel Artificial Membrane Permeability Analysis. Pharmaceuticals 2024, 17, 1024. https://doi.org/10.3390/ph17081024
Niu J, Huang H, Ji M, Zhang W, Huang Y, Ma L, Wang B, Liu Q. Bioequivalence Analysis of Terazosin Hydrochloride Tablets Based on Parallel Artificial Membrane Permeability Analysis. Pharmaceuticals. 2024; 17(8):1024. https://doi.org/10.3390/ph17081024
Chicago/Turabian StyleNiu, Jianzhao, Hanhan Huang, Ming Ji, Wenjing Zhang, Yin Huang, Lingyun Ma, Baolian Wang, and Qian Liu. 2024. "Bioequivalence Analysis of Terazosin Hydrochloride Tablets Based on Parallel Artificial Membrane Permeability Analysis" Pharmaceuticals 17, no. 8: 1024. https://doi.org/10.3390/ph17081024