Riluzole Oral Suspension for the Treatment of Amyotrophic Lateral Sclerosis: Texture and Compatibility with Food Thickeners Evaluation
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
- Nutilis Powder (Nutricia, Zutemer, Netherlands)
- Nutilis Clear (Nutricia)
- RESOURCE® ThickenUp™ (Nestlé Health Science, Vevey, Switzerland)
- Fresubin® Clear Thickener (Fresenius Kabi, Bad Humboldt, Germany)
- THICK & EASY™ Instant Food Thickener (Fresenius Kabi)
- Milli-Q grade water, analytical grade solvents/reagents (Acetonitrile, Trifluoroacetic acid, Ethanol) analytical grade laboratory glassware, disposable plastic syringes and 0.45-µm hydrophilic PTFE syringe filters were used.
2.2. Methods
2.2.1. IDDSI Flow Test (Drink Testing Methods)
2.2.2. Preparation of Samples for the HPLC Analyses of Riluzole 5 mg/mL Oral Suspension-Thickener Mixtures
2.2.3. Determination of Riluzole Assay and Related Substances by HPLC
2.2.4. Determination of Appearance and pH of Riluzole 5 mg/mL Oral Suspension-Thickener Mixtures
3. Results
3.1. IDDSI Flow Test Results
3.2. HPLC Results: Riluzole Assay of Riluzole 5 mg/mL Oral Suspension-Thickener Mixtures
3.3. HPLC Results: Riluzole-Related Substances of Riluzole 5 mg/mL Oral Suspension-Thickener Mixtures
3.4. Appearance and pH of Riluzole 5 mg/mL Oral Suspension-Thickener Mixtures and Placebo Control Samples
4. Discussion
- All Riluzole HPLC assays were within the 90–110% of the label concentration, both at initial time and after two h.
- No related substances were detected, both at initial time and after two h. The only peaks detected in the HPLC chromatograms were unequivocally attributed to Placebo (i.e., the thickener itself).
- No practical pH differences were observed between Riluzole 5 mg/mL oral suspension alone and mixed with the thickeners, except for the Fresubin® Clear Thickener sample, for which a pH decrease was observed (from 7.2 to 6.4), however this pH decrease resulted to have no impact on Riluzole chemical stability.
- No significant changes in appearance were observed after two h.
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Thickening Agent | Stage 1 (Syrup) | Stage 2 (Custard) | Stage 3 (Pudding) |
---|---|---|---|
Nutilis Powder | 2–3 scoops (1) per 200 mL H2O | 3–4 scoops per 200 mL H2O | 4–5 scoops per 200 mL H2O |
Nutilis Clear | 1 scoop (1) per 200 mL H2O | 3 scoops per 200 mL H2O | 6 scoops per 200 mL H2O |
RESOURCE® ThickenUp™ | 1 brimming spoon (2) per 100 mL H2O | 1.5 brimming spoons per 100 mL H2O | 2 brimming spoons per 100 mL H2O |
Fresubin® Clear Thickener | 1 levelled scoop (3) per 100 mL H2O | 3 levelled scoops per 100 mL H2O | 6 levelled scoops per 100 mL H2O |
THICK & EASY™ Instant Food Thickener | 1 scoop (4) per 100 mL H2O | 1.5 scoops per 100 mL H2O | 2 scoops per 100 mL H2O |
Composition | Nutilis Powder (A) | Nutilis Clear (B) | RESOURCE® ThickenUp™ (C) | Fresubin® Clear Thickener (D) | THICK & EASY™ Instant Food Thickener (E) |
---|---|---|---|---|---|
Riluzole 5 mg/mL oral suspension (g) | 2.0 | 2.0 | 2.0 | 2.0 | 2.0 |
Thickening agent (g) | 0.174 | 0.2088 | 0.1566 | 0.1827 | 0.1566 |
Syringe Type | Syringe n° | Replicate n° | Riluzole 5 mg/mL Oral Suspension Lot 1521601 (Development Lot) | |||
---|---|---|---|---|---|---|
Operator n° 1 | Operator n° 2 | |||||
Volume of Liquid (mL) Remaining into the Syringe after 10 s | IDDSI Level | Volume of Liquid (mL) Remaining into the Syringe after 10 s | IDDSI Level | |||
BD Plastipak™ 10 mL (*) | (1) | 1 | 4.0–4.5 mL | 2 | 4.0–4.5 mL | 2 |
2 | 4.0–4.5 mL | 2 | 4.0–4.5 mL | 2 | ||
3 | 4.0–4.5 mL | 2 | 4.0–4.5 mL | 2 | ||
(2) | 1 | 5.0–5.5 mL | 2 | 4.5–5.0 mL | 2 | |
2 | 5.0–5.5 mL | 2 | 4.5–5.0 mL | 2 | ||
3 | 5.0–5.5 mL | 2 | 4.5–5.0 mL | 2 | ||
(3) | 1 | 4.0–4.5 mL | 2 | 3.5–4.0 mL | 1 | |
2 | 4.0–4.5 mL | 2 | 3.5–4.0 mL | 1 | ||
3 | 4.0–4.5 mL | 2 | 3.5–4.0 mL | 1 | ||
IDDSI level AVERAGE (**) | - | 2 | - | 2 |
Syringe Type | Syringe n° | Replicate n° | Riluzole 5 mg/mL Oral Suspension Lot 16,100 (Commercial Lot) | |||
---|---|---|---|---|---|---|
Operator n° 1 | Operator n° 2 | |||||
Volume of Liquid (mL) Remaining into the Syringe after 10 s | IDDSI Level | Volume of Liquid (mL) Remaining into the Syringe after 10 s | IDDSI Level | |||
BD Plastipak™ 10 mL (*) | (1) | 1 | 5.5–6.0 mL | 2 | 5.5–6.0 mL | 2 |
2 | 5.5–6.0 mL | 2 | 5.5–6.0 mL | 2 | ||
3 | 5.5–6.0 mL | 2 | 5.5–6.0 mL | 2 | ||
(2) | 1 | 6.5–7.0 mL | 2 | 5.0–5.5 mL | 2 | |
2 | 6.5–7.0 mL | 2 | 5.0–5.5 mL | 2 | ||
3 | 6.5–7.0 mL | 2 | 6.0–6.5 mL | 2 | ||
(3) | 1 | 5.5–6.0 mL | 2 | 5.0–5.5 mL | 2 | |
2 | 5.5–6.0 mL | 2 | 5.0–5.5 mL | 2 | ||
3 | 5.5–6.0 mL | 2 | 5.0–5.5 mL | 2 | ||
IDDSI level AVERAGE (**) | - | 2 | - | 2 |
Sample | Riluzole Individual Assay mg/mL (% l.c.) (*) | Riluzole Average Assay mg/mL (% l.c.) (*) | |
---|---|---|---|
Control (Riluzole 5 mg/mL oral suspension) | Control— sample 1 | 4.96 (99.2) | 4.99 (99.8) |
Control— sample 2 | 5.01 (100.2) | ||
A: Nutilis Powder—Riluzole 5 mg/mL oral suspension mixture | Time 0— sample 1 | 4.93 (98.6) | 4.97 (99.4) |
Time 0— sample 2 | 5.00 (100.0) | ||
After 2 h— sample 1 | 5.06 (101.2) | 5.06 (101.2) | |
After 2 h— sample 2 | 5.05 (101.0) | ||
B: Nutilis Clear—Riluzole 5 mg/mL oral suspension mixture | Time 0— sample 1 | 5.12 (102.4) | 5.11 (102.2) |
Time 0— sample 2 | 5.10 (102.0) | ||
After 2 h— sample 1 | 5.11 (102.2) | 5.12 (102.4) | |
After 2 h— sample 2 | 5.13 (102.6) | ||
C: RESOURCE® ThickenUp™ —Riluzole 5 mg/mL oral suspension mixture | Time 0— sample 1 | 4.89 (97.8) | 4.93 (98.6) |
Time 0— sample 2 | 4.96 (99.2) | ||
After 2 h— sample 1 | 4.94 (98.8) | 4.96 (99.2) | |
After 2 h— sample 2 | 4.98 (99.6) | ||
D: Fresubin® Clear Thickener—Riluzole 5 mg/mL oral suspension mixture | Time 0— sample 1 | 4.99 (99.8) | 5.03 (100.7) |
Time 0— sample 2 | 5.07 (101.4) | ||
After 2 h— sample 1 | 4.93 (98.6) | 4.95 (98.9) | |
After 2 h— sample 2 | 4.96 (99.2) | ||
E: THICK & EASY™ Instant Food Thickener—Riluzole 5 mg/mL oral suspension mixture | Time 0— sample 1 | 4.96 (99.2) | 4.97 (99.4) |
Time 0— sample 2 | 4.97 (99.4) | ||
After 2 h— sample 1 | 5.03 (100.6) | 5.01 (100.2) | |
After 2 h— sample 2 | 4.98 (99.6) |
Sample | Initial (time 0) | After 2 h | ||
---|---|---|---|---|
Appearance | pH | Appearance | pH | |
Control (Riluzole 5 mg/mL oral suspension) | Slightly brown, opaque homogenous suspension | 8.19 | Slightly brown, opaque homogenous suspension | 8.18 |
A: Nutilis Powder—Riluzole 5 mg/mL oral suspension mixture | Slightly brown, opaque homogenous mixture | 8.02 | Slightly brown, opaque homogenous mixture | 7.99 |
B: Nutilis Clear—Riluzole 5 mg/mL oral suspension mixture | Slightly brown, opaque homogenous mixture | 8.01 | Slightly brown, opaque homogenous mixture | 7.86 |
C: RESOURCE® ThickenUp™—Riluzole 5 mg/mL oral suspension mixture | Slightly brown, opaque homogenous mixture | 7.99 | Slightly brown, opaque homogenous mixture | 8.03 |
D: Fresubin® Clear Thickener—Riluzole 5 mg/mL oral suspension mixture | Slightly brown, opaque homogenous mixture | 7.21 | Slightly brown, opaque homogenous mixture | 6.40 |
E: THICK & EASY™ Instant Food Thickener—Riluzole 5 mg/mL oral suspension mixture | Slightly brown, opaque homogenous mixture | 8.05 | Slightly brown, opaque homogenous mixture | 7.93 |
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Colombo, G.; Artico, R.; Barbareschi, D. Riluzole Oral Suspension for the Treatment of Amyotrophic Lateral Sclerosis: Texture and Compatibility with Food Thickeners Evaluation. J 2020, 3, 275-288. https://doi.org/10.3390/j3030021
Colombo G, Artico R, Barbareschi D. Riluzole Oral Suspension for the Treatment of Amyotrophic Lateral Sclerosis: Texture and Compatibility with Food Thickeners Evaluation. J. 2020; 3(3):275-288. https://doi.org/10.3390/j3030021
Chicago/Turabian StyleColombo, Giuseppe, Roberta Artico, and Daniele Barbareschi. 2020. "Riluzole Oral Suspension for the Treatment of Amyotrophic Lateral Sclerosis: Texture and Compatibility with Food Thickeners Evaluation" J 3, no. 3: 275-288. https://doi.org/10.3390/j3030021
APA StyleColombo, G., Artico, R., & Barbareschi, D. (2020). Riluzole Oral Suspension for the Treatment of Amyotrophic Lateral Sclerosis: Texture and Compatibility with Food Thickeners Evaluation. J, 3(3), 275-288. https://doi.org/10.3390/j3030021