New validated analytical methods for the determination of Tavaborole (An anti-fungal agent)
Avuthu Sai Sheela, Mukthinuthalapati Mathrusri Annapurna*, Rangisetty Spandana Yasaswini
GITAM Institute of Pharmacy, GITAM (Deemed to be) University, Visakhapatnam-530045, India
*Corresponding Author E-mail: mannapurna.mukthinuthalapati@gitam.edu
ABSTRACT:
New spectrophotometric methods have been established for the determination of Tavaborole in pharmaceutical formulations. Tavaborole is an antifungal agent used for the fungal infection of nail (onychomycosis). Tavaborole is chemically known as 5 - Fluoro -1,3 - dihydro -2,1-benzoxaborol -1-ol. Tavaborole has shown absorption maxima at 271 nm in all the methods. A calibration curve was drawn by taking the concentration on the X – axis and their respective absorbance on Y – axis for all the methods. Tavaborole obeys Beer-Lambert’s law over the concentration range 1-100µg/ml for all the above mentioned methods. The linear regression equations were found to be y = 0.0049x + 0.0017(R˛ = 0.9999) and all the methods are validated as per ICH guidelines.
KEYWORDS: Tavaborole, Spectroscopy, Phosphate buffer, Borate buffer, Validation.
INTRODUCTION:
Tavaborole (Figure 1) is an antifungal agent used for the fungal infection of nail and nail bed. FDA has given approval for the treatment of onychomycosis1-3 in July 2014. Tavaborole (C7H6BFO2; Mo. Wt. 151.93 g/mol) is chemically 5 - Fluoro -1,3 - dihydro -2,1-benzoxaborol -1-ol. It acts by inhibiting an essential fungal enzyme required for protein synthesis. This inhibition of protein enzyme (aminoacyl transfer ribonucleic acid) synthesis leads to cell growth termination and causes death of the cell which finally eliminates the fungal infection. Only two liquid chromatographic4-5 methods were available for the determination of Tavaborole (Table 1) and no spectrophotometric methods was developed so far. Therefore, the authors have chosen eight different reagents and two different spectrophotometric techniques i.e. zero order (D0) and first order derivative (D1) in the present study for the determination of Tavaborole in pharmaceutical dosage forms and validated6.
MATERIALS AND METHODS:
Double beam spectrophotometer (Shimadzu Model No. UV - 1800) was used for the present study. For this study quartz cells are used and all the solutions were scanned at 200-400 nm range. Reagents such as phosphate buffers with pH 2.0, 4.0 and 7.0 0.1N HCl, 0.1N NaOH, borate buffer (pH 9.0) were prepared as per IP 2010. 25 mg of Tavaborole was accurately weighed and transferred in to a 25 ml volumetric flask and dissolved in methanol (1000 µg/ml) and a series of dilutions were prepared with respective buffers as per the requirement. Tavaborole is available as topical solution under the brand name KERYDIN (5 %).
Method validation
Zero order spectroscopy (D0)
A series of Tavaborole solutions 1-100 µg/ml were prepared using different buffer solutions - methanol (Method I), water (Method II), phosphate buffer pH 2 (Method III), phosphate buffer pH 4 (Method IV), phosphate buffer pH 7 (Method V), HCl (Method VI), NaOH (Method VII), and 1-80 µg/ml for borate buffer pH 9 (Method VIII) and scanned against their reagent blank at range of 200–400 nm. Tavaborole has shown its λmax at 271 nm in all methods (Figure 2). A calibration curve was drawn by taking the concentration on the X-axis and their respective absorbance on Y-axis for all the methods.
First order derivative spectroscopy (D1)
The individual zero order spectra of Tavaborole obtained in above mentioned methods were converted into their first order derivative spectra with the help of inbuilt software of the instrument. The resultant derivative spectra have shown both maxima and minima in all methods (Figure 3). A calibration curve was constructed by using amplitude against concentration for all the methods.
Precision was studied at three different concentration levels (n=3) and finally the percentage relative standard deviation was calculated whereas the accuracy studies were carried out by standard addition method.
Assay of laboratory prepared solution
Tavaborole API was mixed with the available excipients in the laboratory (5%) and pure Tavaborole was extracted with methanol and further dilutions were made with respective buffers and assay is carried out or all the methods in for zero order as well as first order techniques.
RESULTS AND DISCUSSION:
New spectrophotometric techniques: zero order derivative (D0) and first order derivative (D1)) were developed for the determination of Tavaborole in different reagents such as methanol, water, phosphate buffer (pH 2.0, 4, 7), HCl, NaOH, and borate buffer (pH 9) respectively. A review of previously published methods was shown in Table 1.
Zero order spectroscopy (D0)
The absorption spectrum of Tavaborole has shown (λmax 271 nm) in all the above mentioned methods. Tavaborole obeys Beer-Lambert’s law over the concentration range 1-100 µg/ml for all the methods and 1-80 µg/ml for borate buffer (pH 9) (Table 2). Calibration curves were drawn by taking the concentration on the x-axis and the corresponding absorbance on the y-axis. The linear regression equations are found to be y = 0.0047x + 0.0065 (0.9997), y = 0.004x + 0.0079 (0.9993), y = 0.0041x + 0.0052 (0.9996), y = 0.0049x + 0.0017 (0.9999), y = 0.0051x - 0.0009 (0.9999), y = 0.0047x + 0.0033 (0.9998), y = 0.0085x + 0.0093 (0.9995), y = 0.0076x + 0.001 (0.9997) for methanol, water, phosphate buffer (pH 2.0, 4, 7), HCl, NaOH and borate buffer (pH 9.0) respectively. The percentage RSD in precision and accuracy was found to be <2 in all the above methods indicating that the methods are accurate and precise.
First order derivative spectroscopy (D1)
Tavaborole obeys Beer-Lambert’s law over the concentration range 1-100 µg/ml in all the methods and 1-80 µg/ml in borate buffer (Table 3). Calibration curve was drawn by taking the concentration on the x-axis and the corresponding amplitude on the y-axis. The linear regression equations are found to be y = 0.0023x + 0.0017 (0.9999), y = 0.0017x - 0.0004 (0.9999), y = 0.0017x + 0.0005 (0.9999), y = 0.0023x + 0.0014 (0.9999), y = 0.002x - 0.0001 (0.9999), y = 0.0019x + 0.0019 (0.9997), y = 0.0029x + 0.0024 (0.9998), y = 0.0086x + 0.0059 (0.9998) for methanol, water, phosphate buffer (pH 2,4,7), HCl, NaOH and borate buffer (pH 9) respectively.
Table 1: Review of Previously published articles
|
Method |
Mobile phase (v/v) / Reagent |
λmax (nm) |
Linearity (µg/mL) |
Ref. |
|
HPLC |
Methanol: Acetonitrile (50:50) |
- |
0.05- 4 |
3 |
|
HPLC |
Phosphoric acid (10 mM, pH 2.0): Acetonitrile (70:30) |
220 |
- |
4 |
|
Spectrophotometry |
Methanol, Water, HCl, NaOH, Phosphate buffers (pH 2.0, 4.0 and 7.0) Borate buffer (pH 9.0) |
271 |
1-100
1-80 |
Present methods |
Table 2: Linearity of Tavaborole – Zero derivative spectroscopy
|
Conc. (µg/ml) |
Absorbance |
|||||||
|
Method I |
Method II |
Method III |
Method IV |
Method V |
Method VI |
Method VII |
Method VIII |
|
|
10 |
0.056 |
0.05 |
0.045 |
0.052 |
0.048 |
0.05 |
0.091 |
0.08 |
|
20 |
0.104 |
0.091 |
0.09 |
0.099 |
0.101 |
0.099 |
0.181 |
0.155 |
|
30 |
0.151 |
0.132 |
0.13 |
0.151 |
0.153 |
0.143 |
0.267 |
0.227 |
|
40 |
0.197 |
0.172 |
0.169 |
0.199 |
0.205 |
0.192 |
0.354 |
0.300 |
|
50 |
0.245 |
0.213 |
0.21 |
0.246 |
0.256 |
0.241 |
0.437 |
0.375 |
|
60 |
0.292 |
0.252 |
0.249 |
0.299 |
0.31 |
0.285 |
0.52 |
0.450 |
|
80 |
0.386 |
0.331 |
0.33 |
0.397 |
0.412 |
0.379 |
0.69 |
0.611 |
|
100 |
0.479 |
0.409 |
0.41 |
0.492 |
0.509 |
0.469 |
0.846 |
- |
Figure 2: Absorption spectra of Tavaborole (50 µg/ml) (D0)
Table 3: Linearity of Tavaborole – First derivative spectroscopy (Max: Maxima; Min: Minima)
|
Conc. (µg/ml) |
Method I |
Method II |
Method III |
Method IV |
||||||||
|
Max |
Min |
Amp. |
Max |
Min |
Amp. |
Max |
Min |
Amp. |
Max |
Min |
Amp. |
|
|
10 |
0.011 |
0.014 |
0.025 |
0.006 |
0.011 |
0.017 |
0.006 |
0.011 |
0.017 |
0.007 |
0.014 |
0.021 |
|
20 |
0.020 |
0.027 |
0.047 |
0.012 |
0.021 |
0.033 |
0.012 |
0.022 |
0.034 |
0.013 |
0.025 |
0.038 |
|
30 |
0.031 |
0.042 |
0.07 |
0.018 |
0.032 |
0.05 |
0.018 |
0.033 |
0.051 |
0.019 |
0.059 |
0.059 |
|
40 |
0.037 |
0.056 |
0.093 |
0.025 |
0.042 |
0.067 |
0.025 |
0.043 |
0.068 |
0.024 |
0.076 |
0.076 |
|
50 |
0.048 |
0.067 |
0.115 |
0.030 |
0.055 |
0.085 |
0.032 |
0.054 |
0.086 |
0.030 |
0.095 |
0.095 |
|
60 |
0.051 |
0.087 |
0.138 |
0.036 |
0.065 |
0.101 |
0.037 |
0.064 |
0.101 |
0.037 |
0.077 |
0.114 |
|
80 |
0.078 |
0.109 |
0.183 |
0.049 |
0.136 |
0.136 |
0.049 |
0.085 |
0.135 |
0.048 |
0.105 |
0.153 |
|
100 |
0.094 |
0.133 |
0.227 |
0.061 |
0.108 |
0.169 |
0.062 |
0.108 |
0.168 |
0.060 |
0.131 |
0.191 |
|
Conc. (µg/ml) |
Method V |
Method VI |
Method VII |
Method VIII |
||||||||
|
Max |
Min |
Amp. |
Max |
Min |
Amp. |
Max |
Min |
Amp. |
Max |
Min |
Amp. |
|
|
10 |
0.006 |
0.014 |
0.02 |
0.007 |
0.014 |
0.021 |
0.008 |
0.022 |
0.03 |
0.007 |
0.018 |
0.025 |
|
20 |
0.012 |
0.027 |
0.039 |
0.015 |
0.026 |
0.041 |
0.002 |
0.043 |
0.06 |
0.014 |
0.037 |
0.051 |
|
30 |
0.018 |
0.041 |
0.059 |
0.022 |
0.038 |
0.06 |
0.027 |
0.066 |
0.093 |
0.02 |
0.053 |
0.073 |
|
40 |
0.026 |
0.053 |
0.079 |
0.028 |
0.052 |
0.08 |
0.034 |
0.085 |
0.119 |
0.027 |
0.069 |
0.096 |
|
50 |
0.031 |
0.067 |
0.098 |
0.035 |
0.064 |
0.099 |
0.041 |
0.105 |
0.146 |
0.034 |
0.086 |
0.12 |
|
60 |
0.038 |
0.081 |
0.119 |
0.043 |
0.075 |
0.118 |
0.051 |
0.125 |
0.176 |
0.04 |
0.104 |
0.144 |
|
80 |
0.049 |
0.108 |
0.157 |
0.057 |
0.099 |
0.156 |
0.066 |
0.167 |
0.233 |
0.056 |
0.142 |
0.198 |
|
100 |
0.062 |
0.136 |
0.198 |
0.069 |
0.124 |
0.193 |
0.080 |
0.207 |
0.289 |
- |
- |
- |
Amp.= Amplitude
Figure 3: Overlay first derivative spectra of Tavaborole (D1)
Table 4: Precision studies of Tavaborole
|
Zero order spectroscopy |
||||
|
Conc.(µg/ml) |
Intraday precision: Mean ± SD (% RSD) |
|||
|
Method I |
Method II |
Method III |
Method IV |
|
|
10 |
0.056±0.00015(0.26) |
0.051±0.00015(0.29) |
0.0463±0.00015(0.32) |
0.053±0.0002 (0.37) |
|
20 |
0.105±0.0004(0.38) |
0.092±0.00015(0.16) |
0.0923±0.0002 (0.21) |
0.098±0.0003 (0.3) |
|
30 |
0.153±0.0002(0.13) |
0.133±0.0002(0.15) |
0.132±0.0001 (0.15) |
0.152±0.0003 (0.19) |
|
Conc.(µg/ml) |
Method V |
Method VI |
Method VII |
Method VIII |
|
10 |
0.0496±0.00015 (0.3) |
0.051±0.00015 (0.29) |
0.092±0.00015 (0.16) |
0.081±0.0005 (0.61) |
|
20 |
0.102±0.00015 (0.14) |
0.098±0.0005 (0.51) |
0.182±0.001 (0.54) |
0.156±0.00057(0.36) |
|
30 |
0.154±0.001 (0.64) |
0.144±0.001 (0.69) |
0.268±0.001 (0.37) |
0.228±0.00057 (0.25) |
|
Conc.(µg/ml) |
Interday precision: Mean ± SD (% RSD) |
|||
|
|
Method I |
Method II |
Method III |
Method IV |
|
10 |
0.058±0.002 (0.43) |
0.053±0.0002 (0.46) |
0.047±0.0003 (0.64) |
0.054±0.0002 (0.53) |
|
20 |
0.106±0.005 (0.56) |
0.094±0.0003 (0.38) |
0.093±0.00041(0.45) |
0.099±0.0004 (0.49) |
|
30 |
0.155±0.0006(0.39) |
0.135±0.0005 (0.41) |
0.133±0.00051 (0.39) |
0.153±0.0006 (0.43) |
|
Conc.(µg/ml) |
Method V |
Method VI |
Method VII |
Method VIII |
|
10 |
0.051±0.0002 (0.52) |
0.053±0.0002 (0.56) |
0.094±0.0003 (0.31) |
0.082±0.00058(0.71) |
|
20 |
0.104±0.0003 (0.37) |
0.098±0.0007 (0.78) |
0.183±0.0013 (0.74) |
0.157±0.0008 (0.53) |
|
30 |
0.156±0.0012 (0.81) |
0.145±0.0012 (0.85) |
0.269±0.0015 (0.59) |
0.229±0.0011 (0.49) |
|
First derivative spectroscopy |
||||
|
Intra precision day: Mean ± SD (% RSD) |
||||
|
Conc. µg/ml) |
Method I |
Method II |
Method III |
Method IV |
|
10 |
0.026±0.0001(0.38) |
0.018±0.001(0.55) |
0.018±0.0001(0.55) |
0.0223±0.00015(0.67) |
|
20 |
0.048±0.00015(0.31) |
0.034±0.00015(0.44) |
0.0343±0.00015(0.43) |
0.039±0.00015(0.38) |
|
30 |
0.072±0.0002(0.27) |
0.052±0.0002(0.38) |
0.053±0.0002 (0.377) |
0.06±0.0002 (0.33) |
|
|
Method V |
Method VI |
Method VII |
Method VIII |
|
10 |
0.0216±0.00015(0.69) |
0.023±0.0002(0.86) |
0.031±0.00015(0.48) |
0.026±0.00015(0.57) |
|
20 |
0.04±0.0001(0.25) |
0.042±0.0001(0.23) |
0.061±0.0001(0.16) |
0.052±0.00015 (0.28) |
|
30 |
0.061±0.0002(0.32) |
0.062±0.0002(0.32) |
0.094±0.0002 (0.21) |
0.073±0.00015 (0.20) |
|
Inter precision day: Mean ± SD (% RSD) |
||||
|
Conc.(µg/ml) |
Method I |
Method II |
Method III |
Method IV |
|
10 |
0.027±0.0001(0.61) |
0.019±0.00013(0.72) |
0.018±0.00012 (0.69) |
0.024±0.001 (0.83) |
|
20 |
0.05±0.0002(0.58) |
0.036±0.0002(0.64) |
0.036±0.0002 (0.56) |
0.041±0.0002 (0.61) |
|
30 |
0.075±0.0003(0.46) |
0.054±0.0002 (0.51) |
0.053±0.0002 (0.53) |
0.062±0.0003 (0.59) |
|
Conc.(µg/ml) |
Method V |
Method VI |
Method VII |
Method VIII |
|
10 |
0.023±0.0001 (0.84) |
0.025±0.0002 (0.91) |
0.033±0.0002 (0.79) |
0.028±0.0002 (0.76) |
|
20 |
0.041±0.00016 (0.41) |
0.043±0.0002 (0.55) |
0.062±0.0003 (0.51) |
0.054±0.0002 (0.51) |
|
30 |
0.063±0.0003 (0.59) |
0.064±0.0003 (0.61) |
0.096±0.0006 (0.64) |
0.076±0.0003 (0.47) |
Table 5: Accuracy studies of Tavaborole
|
Zero order spectroscopy |
||||||||||
|
Spiked Conc. |
Formu lation |
Total Conc. |
Conc. obtained (μg/ml) [% Recovery] (RSD) |
|||||||
|
Method I |
Method II |
Method III |
Method IV |
Method V |
Method VI |
Method VII |
Method VIII |
|||
|
10.87 (50%) |
21.75
|
32.62
|
31.49 [96.53] (0.43) |
31.99 [98.06] (0.29) |
32.4 [99.13] (0.32) |
31.62 [98.7] (0.73) |
32.1 [98.40] (0.52) |
31.99 [98.06] (0.29) |
31.99 [98.06] (0.31) |
32.07 [98.3] (0.81) |
|
21.75 (100%) |
21.75
|
43.5
|
43.28 [99.49] (0.38) |
43.26 [99.44] (0.38) |
42.9 [98.62] (0.25) |
42.58 [97.9] (0.85) |
43.01 [98.80] (0.31) |
42.54 [97.79] (0.51) |
41.9 [96.32] (0.54) |
43.10 [99.1] (0.94) |
|
32.62 (150%) |
21.75
|
54.37
|
53.39 [98.19] (0.56) |
52.88 [97.25] (0.15) |
53.1 [97.68] (0.45) |
53.55 [98.5] (0.92) |
54.21 [99.70] (0.31) |
52.99 [97.46] (0.56) |
53.01 [97.49] (0.59) |
53.77 [98.9] (0.88) |
|
First derivative spectroscopy |
||||||||||
|
Spiked Conc. |
Formu lation
|
Total Conc.
|
Conc. obtained (μg/ml) [% Recovery] (RSD) |
|||||||
|
Method I |
Method II |
Method III |
Method IV |
Method V |
Method VI |
Method VII |
Method VIII |
|||
|
10.87 (50%) |
21.75
|
32.62
|
32.51 [99.66] (0.58) |
32.41 [99.35] (0.55) |
32.3 [99.01] (0.56) |
31.97 [98.0] (0.67) |
32.22 [98.77] (0.69) |
32.01 [98.12] (0.86) |
32.01 [98.12] (0.16) |
32.09 [98.37] (0.57) |
|
21.75 (100%) |
21.75
|
43.5
|
42.25 [97.12] (0.38) |
42.99 [98.82] (0.44) |
42.3 [97.24] (0.69) |
42.51 [97.70] (0.38) |
43.46 [99.83] (0.41) |
42.81 [98.41] (0.55) |
42.05 [97.70] (0.37) |
42.59 [97.9] (0.76) |
|
32.62 (150%) |
21.75
|
54.37
|
52.27 [96.13] (0.46) |
52.85 [97.20] (0.38) |
53.3 [98.08] (0.43) |
53.45 [98.30] (0.59) |
52.9 [97.29] (0.59) |
53.98 [99.28] (0.61) |
53.4 [98.21] (0.61) |
53.69 [98.74] (0.47) |
Table 6: Assay of Tavaborole (Label claim: 43.5 mg)
|
Brand |
Method I |
Method II |
Method III |
Method IV |
|||||
|
Zero order derivative spectroscopy |
|||||||||
|
Observed amount (mg) |
% Recovery |
Observed amount (mg) |
% Recovery |
Observed amount (mg) |
% Recovery |
Observed Amount (mg) |
% Recovery |
||
|
I |
43.45 |
99.88 |
43.21 |
99.33 |
43.42 |
99.816 |
43.25 |
99.42 |
|
|
II |
43.41 |
99.79 |
43.33 |
99.60 |
43.39 |
99.747 |
43.33 |
99.60 |
|
|
|
First order derivative spectroscopy |
||||||||
|
I |
43.39 |
99.74 |
43.15 |
99.19 |
43.19 |
99.28 |
43.20 |
99.31 |
|
|
II |
43.21 |
99.33 |
43.24 |
99.40 |
43.26 |
99.44 |
43.05 |
98.96 |
|
|
|
Method V |
Method VI |
Method VII |
Method VIII |
|||||
|
Zero order derivative spectroscopy |
|||||||||
|
Observed Amount (mg) |
% Recovery |
Observed amount (mg) |
% Recovery |
% Recovery |
Observed amount (mg) |
Observed amount (mg) |
% Recovery |
||
|
I |
43.09 |
99.05 |
43.46 |
99.90 |
43.31 |
99.56 |
43.15 |
99.19 |
|
|
II |
43.11 |
99.10 |
43.08 |
99.03 |
43.16 |
99.21 |
43.20 |
99.31 |
|
|
First order derivative spectroscopy |
|||||||||
|
I |
43.27 |
99.47 |
43.26 |
99.44 |
43.19 |
99.28 |
43.07 |
99.01 |
|
|
II |
43.13 |
99.14 |
43.29 |
99.51 |
43.32 |
99.58 |
43.28 |
99.49 |
|
*Mean of three replicates
Table 7: Optical characteristics of Tavaborole – Zero order spectroscopy
|
Parameters |
Method |
|
|||||||
|
I |
II |
III |
IV |
V |
VI |
VII |
VIII |
||
|
Linearity (µg/ml) |
1-100 |
1-100 |
1-100 |
1-100 |
1-100 |
1-100 |
1-100 |
1-80 |
|
|
λmax (nm) |
271 |
271 |
271 |
271 |
271 |
271 |
271 |
271 |
|
|
Molar extinction coefficient (litre/ mole/ cm-1) |
8.508×103 |
7.596×103 |
6.836×103 |
7.900×103 |
7.292×103 |
7.596×103 |
13.82×103 |
12.15×103 |
|
|
Sandell’s sensitivity (µg/cm2/0.001 absorbance unit) |
0.178 |
0.2 |
0.22 |
0.192 |
0.208 |
0.2 |
0.109 |
0.125 |
|
|
Slope |
0.0047 |
0.004 |
0.0041 |
0.0049 |
0.0051 |
0.0047 |
0.0085 |
0.0076 |
|
|
Intercept |
0.0065 |
0.0079 |
0.0052 |
0.0017 |
0.0009 |
0.0033 |
0.0093 |
0.001 |
|
|
Correlation coefficient |
0.9997 |
0.9993 |
0.9996 |
0.9999 |
0.9999 |
0.9998 |
0.0095 |
0.9997 |
|
|
Precision (%RSD) |
Intraday |
0.13-0.38 |
0.15-0.29 |
0.15-0.32 |
0.19-0.37 |
0.14-0.64 |
0.29-0.69 |
0.16-0.54 |
0.25-0.61 |
|
Interday |
0.39-0.56 |
0.38-0.46 |
0.39-0.64 |
0.43-0.53 |
0.37-0.81 |
0.56-0.85 |
0.31-0.59 |
0.49-0.71 |
|
|
Accuracy (% RSD) |
0.38-0.56 |
0.15-0.38 |
0.25-0.45 |
0.73-0.92 |
0.31-0.52 |
0.29-0.56 |
0.31-0.59 |
0.81-0.94 |
|
|
Assay (%) |
99.88 |
99.33 |
99.81 |
99.42 |
99.05 |
99.03 |
99.21 |
99.31 |
|
CONCLUSION:
The new spectrophotometric methods were validated for the determination of Tavaborole and found to be simple, precise and accurate and the methods can be successfully applied for the determination of Tavaborole in pharmaceutical dosage forms.
ACKNOWLEDGMENT:
The authors are grateful to M/s GITAM (Deemed to be University), Visakhapatnam for providing the research facilities and Biophore Pharmaceuticals (India) for providing the gift samples of Tavaborole.
REFERENCES:
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2. Boni EE, Raza Aly, Sheryl LB et al., Efficacy and safety of tavaborole topical solution, 5%, a novel boron-based antifungal agent, for the treatment of toenail onychomycosis: Results from 2 randomized phase-III studies". Journal of the American Academy of Dermatology. 2015; 73 (1): 62–69.
3. Markham A: Tavaborole: first global approval. Drugs 2014 Sep; 74(13): 1555-58.
4. Siva Rao T, Venu Balireddi and Krishna Murthy T. Analytical method development and validation of stability indicating method of RP-HPLC for quantification of Tavaborole related substances: Application to 5% topical solution. European Journal of Biomedical and Pharmaceutical Sciences, 2018; 5(9): 545-550.
5. Tampucci Silvia, Terreni Eleonora, Burgalassi Susi, Chetoni Patrizia, Monti Daniela. Development and Validation of an HPLC-UV Method to Quantify Tavaborole During in Vitro Transungual Permeation Studies. Journal of AOAC International, 2018; 101(2): 437-443.
6. ICH Q2 [R1] validation of analytical procedures: Text and Methodology: November 2005.
Received on 30.12.2019 Modified on 16.01.2020
Accepted on 10.02.2020 © RJPT All right reserved
Research J. Pharm. and Tech. 2020; 13(4):1893-1908.
DOI: 10.5958/0974-360X.2020.00341.8