Background
Methods
Drugs/chemicals/reagents/solvents
Experimental
Mass uniformity
Amount of active compound
System suitability tests (SST)
Preparation of ART and LUM standard solutions
Preparation of sample solutions
Equilibrium solubility
Solution stability
Dissolution of ART and LUM from FDC ART/LUM tablets
Screening study
Optimization of dissolution conditions
Discriminatory power
Validation of the dissolution procedures
Linearity and range
Precision/repeatability
Robustness
Statistical analysis
Results
Mass uniformity
Amount of active compounds
Product | ART | LUM |
---|---|---|
% l.c. (%RSD) | % l.c. (%RSD) | |
Comether® | 104.6 (0.73) | 109.3 (0.72) |
Artel-L® | 108.1 (1.06) | 103.2 (2.15) |
Artemine® | 104.7 (2.92) | 106.1 (0.04) |
ART/LUM | 110.1 (0.34) | 109.8 (0.25) |
ART/LUM-Ea | 90.1 (0.66) | 95.8 (0.63) |
Equilibrium solubility
# | Medium | Solubility (µg/ml) |
---|---|---|
ART | ||
1 | 0.5% w/v Myrj 52/HCl (pH 1.2) | 151 |
2 | 1% w/v Myrj 52/HCl (pH 1.2) | 181 |
3 | 1% w/v Myrj 52/HCl (pH 2.3) | 290 |
4 | 1.5% w/v Myrj 52/HCl (pH 2.3) | 452 |
5 | 2% w/v Myrj 52/HCl (pH 2.3) | 652 |
6 | 0.5% w/v SLS/HCl (pH 1.2) | 323 |
7 | 1% w/v SLS/HCl (pH 1.2) | 337 |
8 | 0.5% w/v Myrj 52/0.05 M ammonium acetate buffer (pH 4.5) | 8 |
9 | 1% w/v Myrj 52/0.05 M ammonium acetate buffer (pH 4.5) | 33 |
10 | 0.5% w/v SLS/0.05 M ammonium acetate buffer (pH 4.5) | 138 |
11 | 1% w/v SLS/0.05 M ammonium acetate buffer (pH 4.5) | 219 |
12 | 0.5% w/v Myrj 52/0.05 M sodium phosphate buffer (pH 6.8) | 22 |
13 | 1% w/v Myrj 52/0.05 M sodium phosphate buffer (pH 6.8) | 37 |
14 | 0.5% w/v SLS/0.05 sodium phosphate buffer (pH 6.8) | 5 |
15 | 1% w/v SLS/0.05 M sodium phosphate buffer (pH 6.8) | 5 |
16 | 0.5% w/v Tween80/0 0.05 M ammonium acetate buffer (pH 4.5) | 24 |
17 | 1% w/v Tween 80/0.05 M ammonium acetate buffer (pH 4.5) | 23 |
18 | 0.5% w/v Tween 80/HCl (pH 1.2) | 10 |
19 | 1% w/v Tween 80/HCl (pH 1.2) | 17 |
LUM | ||
20 | 1% w/v Myrj 52/HCl (pH 2.3) | 626 |
21 | 1.5% w/v Myrj 52/HCl (pH 2.3) | 813 |
22 | 2% w/v Myrj 52/HCl (pH 2.3) | 1033 |
23 | 1% w/v Tween 80/HCl (pH 1.2) | 112 |
24 | 1% w/v Benzalkonium chloride/HCl (pH 1.2) | 93 |
25 | 1% w/v Sodium lauryl sulfate/HCl (pH 1.2) | 59 |
Dissolution of ART and LUM from FDC ART/LUM tablets
Screening study
Time (min) | Factor settings | Mean (%) release | ||
---|---|---|---|---|
A1 | A2 | A3 | ||
30 | 100 | 3.3 | 1.5 | 87.65a |
100 | 1.3 | 1.5 | 80.88ab | |
100 | 3.3 | 0.5 | 77.70b | |
100 | 1.3 | 0.5 | 64.58c | |
50 | 1.3 | 1.5 | 46.92d | |
50 | 3.3 | 1.5 | 45.87d | |
50 | 1.3 | 0.5 | 44.72de | |
50 | 3.3 | 0.5 | 35.86e | |
LSD (0.05) | 9.3 | |||
CV | 3.88 | |||
p-value | 0.01 |
A2 | A3 | Mean (%) release | |
---|---|---|---|
60 | 3.3 | 1.5 | 73.00a |
3.3 | 0.5 | 72.63a | |
1.3 | 1.5 | 71.71a | |
1.3 | 0.5 | 57.15b | |
LSD (0.05) | 6.36 | ||
CV | 4.1 | ||
p-value | 0.001 | ||
A1 | A2 | Mean (%) release | |
100 | 3.3 | 92.52a | |
100 | 1.3 | 76.41b | |
50 | 3.3 | 53.12c | |
50 | 1.3 | 52.45c | |
LSD (0.05) | 6.36 | ||
CV | 4.1 | ||
p-value | 0.001 |
A2 | A3 | Mean (%) release | |
---|---|---|---|
90 | 3.3 | 1.5 | 82.59a |
1.3 | 1.5 | 77.83b | |
3.3 | 0.5 | 76.56b | |
1.3 | 0.5 | 60.73c | |
LSD (0.05) | 4.14 | ||
CV | 2.46 | ||
p-value | 0.000 | ||
A1 | A2 | Mean (%) release | |
100 | 3.3 | 94.17a | |
100 | 1.3 | 79.15b | |
50 | 3.3 | 64.98c | |
50 | 1.3 | 59.42d | |
LSD (0.05) | 6.36 | ||
CV | 4.1 | ||
p-value | 0.000 |
A2 | A3 | Mean (%) release | |
---|---|---|---|
120 | 3.3 | 1.5 | 93.03a |
3.3 | 0.5 | 83.40b | |
1.3 | 1.5 | 81.26b | |
1.3 | 0.5 | 65.69c | |
LSD (0.05) | 4.47 | ||
CV | 2.44 | ||
p-value | 0.01 | ||
A1 | A3 | Mean (%) release | |
100 | 1.5 | 94.01a | |
100 | 0.5 | 87.05b | |
50 | 1.5 | 80.27c | |
50 | 0.5 | 62.03d | |
LSD (0.05) | 4.47 | ||
CV | 2.44 | ||
p-value | 0.000 |
Time (min) | Factor settings | Mean (%) drug release | ||
---|---|---|---|---|
A1 | A2 | A3 | ||
30 | 100 | 1.3 | 1.5 | 87.24a |
100 | 1.3 | 0.5 | 74.81b | |
50 | 1.3 | 0.5 | 70.29b | |
50 | 1.3 | 1.5 | 33.98c | |
100 | 3.3 | 1.5 | 13.05d | |
50 | 3.3 | 0.5 | 9.82de | |
50 | 3.3 | 1.5 | 4.14e | |
100 | 3.3 | 0.5 | 3.68e | |
LSD (0.05) | 8.84 | |||
CV | 6.02 | |||
p-value | 0 | |||
60 | 100 | 1.3 | 1.5 | 93.27a |
100 | 1.3 | 0.5 | 85.2b | |
50 | 1.3 | 0.5 | 81.08b | |
50 | 1.3 | 1.5 | 37.77c | |
100 | 3.3 | 1.5 | 20.36d | |
50 | 3.3 | 0.5 | 14.32e | |
50 | 3.3 | 1.5 | 6.39f | |
100 | 3.3 | 0.5 | 4.76f | |
LSD (0.05) | 5.37 | |||
CV | 3.17 | |||
p-value | 0 | |||
90 | 100 | 1.3 | 1.5 | 96.68a |
100 | 1.3 | 0.5 | 90.52b | |
50 | 1.3 | 0.5 | 86.11b | |
50 | 1.3 | 1.5 | 39.63c | |
100 | 3.3 | 1.5 | 26.23d | |
50 | 3.3 | 0.5 | 17.44e | |
50 | 3.3 | 1.5 | 8.25f | |
100 | 3.3 | 0.5 | 7.07f | |
LSD (0.05) | 5.56 | |||
CV | 3.03 | |||
p-value | 0 | |||
120 | 100 | 1.3 | 1.5 | 99.83a |
100 | 1.3 | 0.5 | 94.96ab | |
50 | 1.3 | 0.5 | 92.83b | |
50 | 1.3 | 1.5 | 40.58c | |
100 | 3.3 | 1.5 | 28.47d | |
50 | 3.3 | 0.5 | 20.61e | |
50 | 3.3 | 1.5 | 10.56f | |
100 | 3.3 | 0.5 | 7.39f | |
LSD (0.05) | 5.14 | |||
CV | 2.63 | |||
p-value | 0 |
Discriminatory power
Validation of the method
Precision/repeatability
# | % Drug release (n = 6) | |||
---|---|---|---|---|
Analyst 1 | Analyst 2 | Analyst 1 | Analyst 2 | |
ART | ART | LUM | LUM | |
1 | 85.27 | 80.24 | 84.63 | 81.22 |
2 | 82.63 | 84.41 | 82.02 | 82.85 |
3 | 82.42 | 82.44 | 85.73 | 88.82 |
4 | 83.60 | 85.42 | 83.53 | 87.01 |
5 | 82.42 | 82.44 | 81.46 | 82.17 |
6 | 86.78 | 83.12 | 86.34 | 85.23 |
Mean | 83.85 | 83.01 | 83.95 | 84.55 |
SD | 1.8 | 1.79 | 1.97 | 2.98 |
%RSD | 2.15 | 2.16 | 2.35 | 3.52 |
Mean | 83.43 | 84.25 | ||
SD | 0.59 | 0.42 | ||
%RSD | 0.35 | 0.50 |
Robustness
Time (min) | pH | Agitation speed (rpm) | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
ART | LUM | ART | LUM | |||||||||
1.4 | 1.6 | 1.8 | 1.4 | 1.6 | 1.8 | 98 | 100 | 102 | 98 | 100 | 102 | |
30 | 73.2 | 75.7 | 80.0 | 77.1 | 79.6 | 78.7 | 77.4 | 79.3 | 76.9 | 73.0 | 78.1 | 72.6 |
60 | 80.9 | 84.6 | 85.9 | 88.2 | 85.8 | 84.8 | 82.2 | 85.7 | 84.7 | 83.2 | 84.6 | 85.9 |
90 | 89.0 | 91.3 | 92.9 | 91.1 | 95.5 | 96.1 | 88.8 | 90.4 | 87.6 | 92.9 | 96.0 | 96.4 |
120 | 94.0 | 94.7 | 96.5 | 95.2 | 98.1 | 99.0 | 89.5 | 93.3 | 91.7 | 98.9 | 99.1 | 98.9 |
Average at 60 min | 83.81 ± 2.62 | 86.24 ± 1.75 | 84.20 ± 1.79 | 84.59 ± 1.34 | ||||||||
%RSD | 3.13 | 2.04 | 0.02 | 0.01 | ||||||||
p > 0.05 |