Compatibility of Commonly Used Active Pharmaceutical Ingredients in a Ready-to-Use Oral Suspending Vehicle
Abstract
:1. Introduction
2. Materials and Methods
2.1. Reagents, Reference Standards, and Equipment
2.2. Titration
2.3. Chromatographic Conditions
2.4. Validation of Chromatographic Methods
2.5. Formulating the Suspensions
2.5.1. SyrSpend® SF PH4 NEO
2.5.2. SyrSpend® SF PH4 Liquid
2.6. Forced-Degradation Studies: Stability-Indicating Characteristics
2.7. Stability Study
3. Results
4. Discussion
4.1. Amoxicillin
4.2. Clozapine
4.3. Indomethacin
4.4. Levodopa/Carbidopa
4.5. Levothyroxine Sodium (T4)
4.6. Lomustine
4.7. Methyldopa
4.8. Procarbazine
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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API | Concentration (mg/mL) | Pharmaceutical Class | Vehicle |
---|---|---|---|
Amoxicillin trihydrate | 50 | Antibiotic | SyrSpend® SF PH4 liquid |
Clozapine | 25 | Atypical antipsychotic | SyrSpend® SF PH4 liquid |
Indomethacin | 5 | Analgesic | SyrSpend® SF PH4 NEO |
Levodopa/ Carbidopa | 10/ 2.5 | Central nervous system agent/decarboxylase inhibitor | SyrSpend® SF PH4 liquid |
Levothyroxine Sodium (T4) | 0.025 | Hormone | SyrSpend® SF PH4 liquid |
Lomustine | 4 and 10 | Alkylating agents | SyrSpend® SF PH4 liquid |
Methyldopa | 50 | Antihypertensives | SyrSpend® SF PH4 liquid |
Procarbazine | 10 | Alkylating agents (malignancies) | SyrSpend® SF PH4 liquid |
API | Mobile Phase Composition (v/v) | Work Concentration (μg/mL) a/Injection Volume (µL) | Column | Flux (mL/min) | Ultraviolet Detection Wavelength (nm) |
---|---|---|---|---|---|
Clozapine | Methanol:triethylamine:water (800:0.75:200) | 100/10 | C8, 4.6 mm × 250 mm at 25 °C | 1.0 | 257 |
Indomethacin | Acetonitrile (550:450 v/v) with pH set to 8.0 with sodium hydroxide 1M | 500/0.5 | C8, 2.1 mm × 100 mm at 30 °C | 0.3 | 290 |
Levodopa/Carbidopa | Alcohol:Buffer monobasic sodium phosphate pH 2.2 (5:95) | 250/20 | C18, 4.6 mm × 250 mm at 25 °C | 1.0 | 280 |
Levothyroxine Sodium (T4) | 750 mL of ultra-purified water + 2 mL of phosphoric acid:acetonitrile (70:30) | 5/50 | L10, 4.6 mm × 250 mm at 25 °C | 1.0 | 225 |
Lomustine | Acetonitrile:water (1:1) | 100/20 | C18, 4.6 mm × 250 mm at 40 °C | 1.5 | 230 |
Methyldopa | Phosphate buffer pH 3.0:methanol (85:15) | 500/20 | C18, 4.6 mm × 250 mm at 25 °C | 1.0 | 280 |
Procarbazine | 0.1M Dibasic phosphate buffer pH 7.0:methanol:acetonitrile (810:90:100). | 100/20 | C18, 4.6 mm × 250 mm at 25 °C | 1.0 | 254 |
APIs | Linearity | Specificity | Precision | Accuracy | ||||||
---|---|---|---|---|---|---|---|---|---|---|
Range (µg/mL) | Analytical Curve | R2 | F | LOD (µg/mL) | LOQ (µg/mL) | Discrepancy (%) | Repeatability (CV, %) | Intermediate Precision (CV, %) | Recovery (%) | |
Clozapine | 70.07-130.13 | y = 583841x − 1086406 | 0.9996 | 15719.29 | 0.005 | 0.014 | 1.98 | 0.12 | 2.05 | 100.19 |
Indomethacin | 359.80-668.20 | y = 0.039x + 0.0646 | 0.9978 | 3009.17 | 0.43 | 1.30 | 1.02 | 1.47 | 3.83 | 99.73 |
Levodopa/ Carbidopa | 175.56-326.04 | y = 15.92x − 271.22 | 0.9937 | 2041.11 | 0.01 | 0.03 | 0.56 | 0.17 | 3.22 | 100.54 |
Levothyroxine Sodium (T4) | 3.52-6.54 | y = 56.01x − 41.64 | 0.9910 | 712.06 | 0.02 | 0.06 | 1.68 | 0.81 | 0.77 | 101.62 |
Lomustine | 70.56-131.04 | y = 14.941x − 30.711 | 0.9968 | 2004.18 | 0.14 | 0.43 | 1.39 | 0.21 | 4.13 | 100.03 |
Methyldopa | 350.07-650.13 | y = 239370x − 4717139 | 0.9994 | 10018.78 | 0.0144 | 0.043 | 0.453 | 0.32 | 0.75 | 99.70 |
Procarbazine | 72.52-134.68 | y = 30.711 + 14.941 | 0.9991 | 6987.13 | 0.0003 | 0.001 | 1.94 | 0.71 | 0.61 | 100.05 |
API | HCl | NaOH | UV | Heat | H2O2 |
---|---|---|---|---|---|
%d * | %d | %d | %d | %d | |
Clozapine | −11.96 | −85.17 | −50.76 | −5.11 | −8.11 |
Indomethacin | −66.24 | −100.00 | −5.28 | −12.35 | −2.09 |
Levodopa/Carbidopa | 1.38/4.21 | 0.43/−28.56 | −0.23/2.74 | 1.69/3.31 | −0.87/−1.59 |
Levothyroxine Sodium (T4) | −59.08 | −58.34 | −51.32 | −80.02 | −99.95 |
Lomustine | −99.66 | −99.02 | −29.57 | −99.64 | 6.53 |
Methyldopa | −0.29 | −97.84 | −0.34 | −3.35 | −0.89 |
Procarbazine | −35.30 | −72.24 | −28.19 | −70.79 | −98.86 |
Elapsed Time (Days) | %Recovery | |||
---|---|---|---|---|
Refrigerated Temperature (2–8 °C) | Controlled Room Temperature (20–25 °C) | |||
Amoxicillin 50 mg/mL | ||||
T = 0 | 100.00 ± 0.07 | 100.00 ± 0.07 | ||
T = 7 | 101.07 ± 0.23 | 99.37 ± 0.37 | ||
T = 14 | 99.11 ± 0.05 | 97.41 ± 0.11 | ||
T = 30 | 101.40 ± 0.02 | 94.38 ± 0.02 | ||
Clozapine 25 mg/mL | ||||
T = 0 | 100 ± 0.22 | 100 ± 0.22 | ||
T = 7 | 99.98 ± 0.60 | 98.59 ± 0.45 | ||
T = 14 | 98.54 ± 0.31 | 98.96 ± 0.42 | ||
T = 30 | 99.03 ± 0.18 | 99.26 ± 0.45 | ||
T = 60 | 99.21 ± 0.45 | 97.05 ± 0.34 | ||
T = 90 | 99.39 ± 0.17 | 96.27 ± 0.42 | ||
Indomethacin 5 mg/mL | ||||
T = 0 | 100.00 ± 0.35 | 100.00 ± 1.66 | ||
T = 7 | 99.93 ± 0.05 | 99.24 ± 1.01 | ||
T = 14 | 98.49 ± 0.11 | 98.86 ± 0.03 | ||
T = 30 | 95.56 ± 0.03 | 99.27 ± 0.07 | ||
T = 60 | 95.48 ± 0.04 | 100.85 ± 0.03 | ||
T = 90 | 95.81 ± 0.07 | 100.78 ± 0.08 | ||
Levodopa 10 mg/mL + Carbidopa 2.5 mg/mL | ||||
Levodopa | Carbidopa | Levodopa | Carbidopa | |
T = 0 | 100.00 ± 2.38 | 100.00 ± 0.84 | 100.00 ± 2.38 | 100.00 ± 0.84 |
T = 7 | 101.69 ± 0.28 | 100.06 ± 0.90 | 98.36 ± 0.37 | 98.11 ± 1.78 |
T = 14 | 100.38 ± 1.77 | 99.46 ± 0.78 | 98.06 ± 0.14 | 97.80 ± 0.03 |
T = 30 | 100.54 ± 0.96 | 98.39± 0.69 | 98.88 ± 0.07 | 97.82 ± 0.02 |
T = 60 | 100.72 ± 0.55 | 98.91 ± 0.87 | 98.93± 0.09 | 97.88 ± 0.04 |
T = 90 | 100.63 ± 0.54 | 98.79 ± 1.03 | 98.44 ± 0.31 | 97.83 ± 0.26 |
Levothyroxine Sodium (T4) 0.025 mg/mL | ||||
T = 0 | 100.0 ± 0.55 | NP | ||
T = 7 | 96.52 ± 0.20 | NP | ||
T = 14 | 96.26 ± 0.55 | NP | ||
T = 30 | 96.22 ± 0.55 | NP | ||
T = 60 | 96.00 ± 1.4 | NP | ||
T = 90 | 96.06 ± 0.87 | NP | ||
Lomustine 4 mg/mL | ||||
T = 0 | 100 ± 0,29 | NP | ||
T = 7 | 97.41 ± 0.31 | NP | ||
T = 14 | 97.29 ± 0.17 | NP | ||
T = 30 | 97.35 ± 0.19 | NP | ||
T = 60 | 97.24 ± 0.88 | NP | ||
T = 90 | 97.15 ± 0.34 | NP | ||
Lomustine 10 mg/mL | ||||
T = 0 | 100 ± 0.34 | NP | ||
T = 7 | 99.33 ± 0.22 | NP | ||
T = 14 | 98.55 ± 0.17 | NP | ||
T = 30 | 99.13 ± 0.19 | NP | ||
T = 60 | 98.63 ± 0.94 | NP | ||
T = 90 | 98.57 ± 0.13 | NP | ||
Methyldopa 50 mg/mL | ||||
T = 0 | 100.00 ± 0.2 | NP | ||
T = 7 | 99.17 ± 0.14 | NP | ||
T = 14 | 99.81 ± 0.42 | NP | ||
T = 30 | 99.35 ± 0.44 | NP | ||
T = 60 | 99.44 ± 0.2 | NP | ||
T = 90 | 99.52 ± 0.42 | NP | ||
Procarbazine 10 mg/mL | ||||
T = 0 | 100.00 ± 0.23 | NP | ||
T = 7 | 99.75 ± 1.43 | NP | ||
T = 14 | 100.10 ± 0.42 | NP | ||
T = 30 | 100.67 ± 1.22 | NP | ||
T = 60 | 80.44 ± 1.23 | NP |
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Mansourian, M.; Dijkers, E.; Silva, C.C.V.; Polonini, H.C. Compatibility of Commonly Used Active Pharmaceutical Ingredients in a Ready-to-Use Oral Suspending Vehicle. Pharmaceutics 2023, 15, 2388. https://doi.org/10.3390/pharmaceutics15102388
Mansourian M, Dijkers E, Silva CCV, Polonini HC. Compatibility of Commonly Used Active Pharmaceutical Ingredients in a Ready-to-Use Oral Suspending Vehicle. Pharmaceutics. 2023; 15(10):2388. https://doi.org/10.3390/pharmaceutics15102388
Chicago/Turabian StyleMansourian, Mercedeh, Eli Dijkers, Carolina C. V. Silva, and Hudson C. Polonini. 2023. "Compatibility of Commonly Used Active Pharmaceutical Ingredients in a Ready-to-Use Oral Suspending Vehicle" Pharmaceutics 15, no. 10: 2388. https://doi.org/10.3390/pharmaceutics15102388
APA StyleMansourian, M., Dijkers, E., Silva, C. C. V., & Polonini, H. C. (2023). Compatibility of Commonly Used Active Pharmaceutical Ingredients in a Ready-to-Use Oral Suspending Vehicle. Pharmaceutics, 15(10), 2388. https://doi.org/10.3390/pharmaceutics15102388