Electrochemical Behavior and Differential Pulse Polarographic Determination of Flucloxacillin in Pure and Pharmaceutical Dosage Forms Using Dropping Mercury Electrode

 

Abdul Aziz Ramadan*, Hasna Mandil**, Reham Abu-Saleh

Department of Chemistry, Faculty of Science, University of Aleppo, Syria.

 

ABSTRACT:

Electrochemical behavior and differential pulse polarographic determination of flucloxacillin (FLUX) in pure and pharmaceutical dosage forms using drop mercury electrode (DME) has been studied. The method involves the electrochemical behavior of flucloxacillin at DME by differential pulse polarographic analysis (DPPA). Various parameters (electrolyte, pulse time, pulse amplitude, etc.) affecting the FLUX determination were examined. Different buffer solutions were used over a wide pH range (2.5–10.0). The best definition of the analytical signals was found in Britton–Robinson buffer (0.04 M) at pH 4.0. Under the optimum conditions, liner calibration graph, I_p=f(C_FLUX) was obtained in the concentration ranges of 1x10^-7 M (0.0494 μg.mL^-1) to 2x10^-5 M (9.8780 μg.mL^-1), at -975 to -1000 mV (versus Ag/AgCl) with relative standard deviations (RSD) did not exceed 2.1% for the concentrations of FLUX (0.0494 μg.mL^-1). Regression analysis showed a good correlation coefficient (R²=9997) between I_p and concentration over the mentioned range. The limit of detection (LOD) and the limit of quantification (LOQ) were to be 0.0034 and 0.0102 μg.mL^-1, respectively. The proposed method was validated for linearity, precision and accuracy, repeatability, sensitivity (LOD and LOQ), robustness and specificity. The developed method is applicable for the determination of FLUX in pure and different dosage forms in presence a same amount of amoxicillin ^(AMOX) with average recovery of 99.8 to 101.2% and the results are in good agreement with those obtained by the HPLC reference method.

 

 

 

INTRODUCTION:

Flucloxacillin is a member of the beta-lactamase-stable group of penicillins derived from the penicillin nucleus used in the treatment of bacterial infections, usually used to treat the gram-positive organisms [1]. It can be used in the treatment of some skin infections like boils, meningitis among other bacterial infections. It causes muscle pains as one of its side effects and it is not used in persons who react to penicillins [2,3]. Flucloxacillin, [3-(2-chloro-6-fluorophenyl)-5-methylisoxazol-4-yl] carbonyl]amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo [3. 2 .0] heptane 2-carboxylate] are the penicillinase- resistant penicillins.

 

It is used as an antibiotic [4]. It is normally synthesized for use pharmaceutically usually as the sodium salt and less so, the magnesium salt [5]. Freely soluble in water and in methanol. The chemical formula of flucloxacillin sodium is C₁₉H₁₆ClFN₃NaO₅S.H₂O, its molecular weight is 493.9 g.moL^-1. The chemical structure of flucloxacillin sodium, see scheme 1.

 

 

Scheme 1: Chemical structure of Flucloxacillin.

 

The hydrolysis of flucloxacillin at pH 4.9 yields a degradation product which is polaro-graphically oxidizable. It gives a diffusion-controlled anodic polarographic wave with a half-wave potential at-0.24 V (versus Ag/AgCl) [6]. A potentiometric method for determination of flucloxacillin is developed. The method involves development of a flucloxacillin sensor with a membrane consisting of Aliquat-flucloxacillin as an electro active material in poly vinyl chloride matrix membrane plasticized with ortho nitro phenyl-octyl ether or dioctylphthalate. The sensor shows fast, stable and reproducible response over the concentration range of 1.0×10⁻⁵–1.0×10⁻² M flucloxacillin and pH ranges of 6–11 and 7–11 for o-nitro phenyl octyl ether (o-NPOE) and dioctylphthalate (DOP) plasticized based membrane sensors, respectively [7]. Some nitrophenols are proposed as chromogenic reagents for the spectrophotometric determination of flucloxacillin. Beer's low is valid over the concentration range 2.0–40 μg.mL⁻¹ of flucloxacillin [8]. The visible spectrophotometric methods for the determination of flucloxacillin. These methods are based on the formation of ion-pair complex of the flucloxacillin, with bromocresol green in acidic medium. The colored products are extracted with chloroform and measured spectrophotometrically at 433 nm for flucloxacillin. Beer’s law was obeyed in the concentration range of 0.5-2.5 mg.mL^-1 with relative standard deviation of 0.28% for flucloxacillin [9]. An isocratic ion exchange high performance liquid chromatography method was developed for the simultaneous determination of flucloxacillin and amoxicillin in pharmaceutical formulations for injections. The separation was made by a ZORBAX 300-SCX column using 0.025 M ammonium dihydrogen phosphate (adjusted to pH 2.6 with phosphoric acid)–acetonitrile (95:5) as mobile phase [10]. A simple, precise, fast and accurate HPLC method has been developed for the simultaneous estimation amoxicillin and flucloxacillin in capsules. The analytes were resolved, by using a mobile phase mixture of buffer (prepared from 0.001 M diammonium hydrogen orthophosphate and 0.04 M tetra butyl ammonium bromide pH adjusted to 7.0±0.1 with ortho phosphoric acid) and acetonitrile in the ratio (90:10, v/v), on a strong cation exchange column, (LUNA SCX, 250mm x 4.6mm I.D. 5 μm particles).The retention times for amoxicillin and flucloxacillin were found to be 3.828 and 5.89 min, respectively [11].

 

In the present work, electrochemical behavior and differential pulse polarographic determination of flucloxacillin in pure and pharmaceutical dosage forms using dropping mercury electrode was applied. The method is an easy, fast and sensitive for the determination this compound in pure and in pharmaceuticals.

 

 

EXPERIMENTAL:

Reagents:

Working reference standard of flucloxacillin (99.2%) was supplied by D.K. Pharmachem Pvt. Ltd INDIA, (Mfg.12-2017, Exp. 11-2020). Lithium perchlorate trihydrate, di-Sodium tetraborat decahydrat (borax), di-Sodium hydrogen phosphate dodecahydrate, Sodium acetate trihydrate, Sodium chloride, Sodium hydroxid, Perchloric acid (70%), ortho-Phosphoric acid (85%), Acetic acid (100%), Boric acid (100%) were of GR for analysis purchased from MERCK.

 

Instruments and apparatus:

A Metrohm 746 VA processor, A Metrohm 747 VA stand with a dropping mercury electrode (DME) as a working electrode, an auxiliary platinum electrode and a reference electrode, double junction type, (Ag/AgCl) saturated with a 3.0 M KCl solution and the three-electrode cell were used. All measurements were done at room temperature 25±5 ^oC. Highly pure nitrogen gas (99.999 %) was used for de-oxygenation. pH meter from Radiometer company model ion check was used for the studying and monitoring the pH effects. The diluter pipette model DIP-1 (Shimadzu), having 100 μL sample syringe and five continuously adjustable pipettes covering a volume range from 20 to 5000 μL (model PIPTMAN P, GILSON), were used for preparation of the experimental solutions. A ultrasonic processor model powersonic 405 was used to sonicate the sample solutions. Electronic balance (Sartorius-2474; d=0.01 mg) was used for weighing the samples.

 

Supporting electrolyte:

Sodium acetate-acetic acid (HAc-NaAc), Britton Robinson, H₃PO₄-Na₂HPO₄, disodium tetraborat, lithium perchlorate, sodium chloride buffers 0.2000 mol.L^-1 at pH (2.5-10.0) were used.

 

A stock standard solution of flucloxacillin (1x10^-4 mol.L^-1):

This solution was prepared by dissolving 49.79 mg from flucloxacillin in 100 mL double distilled deionized ^water (1x10^-3 mol.L^-1), then dilute 10.000 mL from this solution to 100 mL (1x10^-4 mol.L^-1).

 

Working solutions:

The stock solutions were further diluted to obtain working solutions daily just before use in the ranges of FLUX: 0.100, 0.200, 0.400, 0.800, 1.000, 2.000, 4.000, 5.000, 8.000, 10.000 ,12.000 , 16.000 and 20.000 μmol.L^-1 (0.0494, 0.0988, 0.1976, 0.3951, 0.4939, 0.9878, 1.9756, 2.4695, 3.9512, 4.9390, 5.9268, 7.9024 and 9.8780 μg.mL^-1) by dilution of the volumes: 0.025, 0.050, 0.100, 0.200, 0.250, 0.500, 1.000, 1.250, 2.000, 2.500, 3.000, 4.000 and 5.000 mL from stock standard solutions were transferred into 25 mL volumetric flask. 5.0 mL of supporting electrolyte were added, and diluted with double distilled deionized ^water to the mark. Ultrapure mercury from Metrohm Company was used throughout the experiments.

 

^{Sample preparation:}

^{A commercial formulations (as capsule) were used for the analysis of FLUX by using} DPPA ^with DME^{. The pharmaceutical formulations were subjected to the analytical procedures:}

^{(1)        Amoxipen capsule, BARAKAT PHARMACEUTICAL, Aleppo–SYRIA, each capsule contains: 250 mg of FLUX and 250 mg AMOX (Exp. 03.2020).}

^{(2)        Amoxam capsule, IBN HAYYAN, Homs–SYRIA, each capsule contains: 250 mg of FLUX and 250 mg AMOX (Exp. 06.2020).}

^{(3)        Penifloxam capsule, APHAMEA, Hama–SYRIA, each capsule contains: 250 mg of FLUX and 250 mg AMOX (Exp. 04.2020).}

^{(4)        Floxin capsule, ALBALSAM PHARMA, Homs-SYRIA, each capsule contains: 250 mg of FLUX and 250 mg AMOX (Exp. 04.2020).}

^{(5)        Maxipen capsule, ASIA, Aleppo–SYRIA, each capsule contains: 250 mg of FLUX and 250 mg AMOX (Exp. 06.2020).}

 

^{Stock solutions of pharmaceutical formulations:}

Contents of 20 capsules of each studied pharmaceutical formulations were weighted accurately, crushed to a fine powder and mixed well. Equivalent weight of contents of one capsule, was solved in 50 mL double distilled deionized ^water by using ultrasonic, filtered over a 100 mL flask and diluting to 100 mL with double distilled deionized ^water, which content as the follows: 2500 μg.mL^-1 for all studied pharmaceutical formulations content 250 mg/cap.

 

^{Working solutions of pharmaceuticals:}

_{These solutions were prepared daily by diluting 100 µL (0.001 mL) from stock solutions of pharmaceutical formulations, adding 20 mL from supporting electrolyte, then diluting to 100 mL with double distilled deionized water (each solution contents 2.5 μg.mL-1 of FLUX).}

 

^{Analytical procedure:}

^{25 mL of working standard of flucloxacillin or working solutions of pharmaceuticals was transferred to the cell. The solution was deoxygenated with N2 gas for 300 s. The potential range studied was from -400 to -1400 mV versus Ag/AgCl with differential pulse polarographic analysis using drop mercury electrode in the optimum conditions were applied.}

 

Results and discussion:

^{Differential pulse polarographic behavior:}

The polarograms for concentration 0.10-20.0 µmol.L^-1 (0.0494-9.8780 μg.mL^-1) of FLUX in the optimal conditions (supporting electrolytes, pH, scan rate, initial potential, final potential, etc.) using DPPA at DME were studied. The best definition of the analytical signals was found in Britton–Robinson (0.04 M) buffer (pH 4.0) at         -975 to -1000 mV (versus Ag/AgCl).

 

^{The effect of supporting electrolytes (buffer):}

The electrochemical behavior of flucloxacillin was studied in various supporting electrolytes such as (sodium chloride, Britton Robinson, lithium perchlorate, sodium acetate trihydrate ⁽HAc-NaAc), disodium tetraborat, di-sodium hydrogen phosphate dodecahydrate was studied at pH (2.5-10.0). The best definition of the analytical signals was found in Britton- Robinson buffer (pH 4.0) ^{at concentration 0.04 M. The effect of supporting electrolytes (buffer) on the Ip and Ep was studied. The values of Ep were -943, -975, -980, -985,-1000 and -1010 mV for the mention buffers, respectively,} see Figure 1^. The effect of the concentration of Britton -Robinson was tested over the 4, 8, 10, 20, 30, 35, 40, 50, 60, 70, 80, 90 and 100 mM. The DPPA at DME of 8.0 µM of FLUX with the varying concentrations of supporting electrolyte was studied^. The values ^{of Ip} increase with increasing concentration of supporting electrolyte of ^{4 to 40 mM,} then become semi-fixed until concentration of supporting electrolyte 100 mM^, while E^p remains quasi-static.

 

 

Fig.1:The effect of buffer solutions on polarograms of FLUX (8.00 µM) using DPPA at DME buffers (0.04 M) at pH 4.0: ^{1-Britton-Robinson, 2-NaCl, 3-Na2HPO4.12H2O, 4-Na2B4O7.10H2O, 5-NaCH3COO. 3H2O, 6-LiClO4.3H2O} (Purge gas N₂, purge time 300 s, sweep rate 4 mV/s, U. amplitude -100 mV, t. meas 32 ms, t. pulse 35 ms, t. step 2 s, U. step 8 mV, temperature 25°± 5°C).

 

^{The effect of pH:}

_{The influence of pH from 2.5 to 10.0 using Britton–Robinson (0.04 M) buffer on Ip and Ep was studied. The values of Ip increase with increasing pH value of 2.5 to 4.0, then decrease until pH 6.0 and finally become semi-fixed until pH 10. While Ep values are growing a positive value from-1044 mV (when pH 2.5) to-930 mV (when pH 5.0) then become semi-fixed until pH 10, see Figures 2,3.}

 

 

Fig.2: The effect of pH solution on I_p of FLUX (8,00 µM) using DPPA at DME buffers (0.04 M):

1- Britton-Robinson, 2-Na₂HPO₄.12H₂O, 3-NaCl, 4-Na₂B₄O₇. 10H₂O, 5-NaCH₃COO. 3H₂O, 6-LiClO₄. 3H₂O (Purge gas N₂, purge time 300 s, sweep rate 4 mV/s, U. amplitude-100 mV, t. meas 32 ms, t. pulse 35 ms, t. step 2 s, U. step 8 mV, temperature 25°±5°C).

 

 

Fig.3: The effect of pH solution on E_p of FLUX (8,00 µM) using DPPA at DME containing buffer Britton-Robinson (0.04 M) (Purge gas N₂, purge time 300 s, sweep rate 4 mV/s, U. amplitude-100 mV, t. meas 32 ms, t. pulse 35 ms, t. step 2 s, U. step 8 mV, temperature 25°±5°C).

 

The effect of negative pulse amplitude (U.ampl):

The effect of negative pulse amplitude (U.ampl) between -10 to -100 mV on I_p and E_p, I_p linearly increases with increasing amplitude value until -100 mV. While E_p stay semi-fixed. The value -100 mV was better than another’s.

 

^{The effect of initial and final potential}

^{The effect of initial and final potential on the Ip and Ep was studied. It was found that better initial potential was -400 mV and better final potential was -1400 mV.}

 

^{The effect of temperature and time:}

^{The effect of temperature and time on the electrochemical behavior of FLUX was studied at different values (15-35oC and 5-60 min) by continuous monitoring of the Ip. It was found that, the value of Ip was not affected by temperature between 20 to 30oC (the temperature at 25±5°C was used). The effect of waiting time was determined at laboratory ambient temperature (25±5°C). It was found that, the value of Ip was not affected by time between 5 to 60 min.}

 

The effect of time pulse (t.pulse):

The effect of time pulse (35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95 and 100 ms) on polarograms was as the follows: I_p decreases with increasing time pulse and E_p has become increasingly positive value (-975 to -945 mV) with increasing t.pulse. The peak was more symmetrical and I_p was the highest when the t. pulse value of 35 ms.

 

The effect of time interval for voltage step (t.step):

I_p linearly increases with increasing t.step (0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.5, 2.0 and 2.5 s), while E_p has become increasingly positive value (-1015 to -975 mV) with increasing t.step. The value of the preferred t.step was 2 s.

 

The effect of measurement time (t.meas):

I_p increases with increasing t.meas. (2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 30, and 32 ms), while E_p remains quasi-static. The value of the preferred t.meas. was 32 ms.

^{The optimum parameters established for determination of FLUX using DPPA on} DME ^{showed in Table 1.}

 

Table 1: The optimum parameters established for determination of FLUX using DPPA on DME.

parameters	Operating modes
Working electrode	Dropping mercury electrode (DME)
Supporting electrolytes (buffer)	Britton–Robinson 0.04 M
pH	4.0
Solvent flucloxacillin	double distilled deionized water
Purge gas	Pure N2
Purge time	300 s
Initial potential	-400 mV
Final potential	-1400 mV
Scan rate	4 mV/s
t. meas	32 ms
Value of pulse amplitude	-100 mV
t. pulse	35 ms
t. step	2s
Temperature of solution	25°±5°C

 

Calibration curves:

Calibration curves for the determination of flucloxacillin using differential pulse polarographic analysis on drop mercury electrode with negative amplitude in Britton–Robinson (0.04 M) buffer at pH 4.0 were applied. One peak was observed in the range -975 to -1000 mV (Ep). The peak current (Ip) was proportional to the concentration of FLUX over the ranges 0.0494-9.8780 μg.mL-1 (0.100-20.000 μmol.L-1). The polarograms in the optimum conditions using DPPA at DME of FLUX at different concentrations show in Figure 4. The regression equation and correlation coefficient (R2) were as the follows: y= -41.952x- 0.7611, R2= 0.9997; y: Ip, nA and x: CFLUX, μg.mL-1, see Figure 5.

 

 

 

 

 

^{Analytical results:}

Determination of FLUX using DPPA on DME in the optimum conditions using analytical curves, I_p=f(C_FLUX), showed that the accuracy was ready over the ranges of FLUX concentration between (0.0494-9.8780 µg.mL^-1). The relative standard deviation (RSD) not more than 2.1%, see Table 2. Limit of detection (LOD) and limit of quantitation (LOQ) for the determination of FLUX by this method were as the follows : 0.0034 and 0.0102 µg.mL^-1, respectively.

 

Fig.4: The polarograms in the optimum conditions using DPPA on DME of FLUX in Britton-Robinson buffer (0.04 M) at pH 4.0 at concentrations: (1-0.0494, 2-0.0988, 3-0.1976, 4-0.3951, 5-0.4939, 6-0.9878, 7-1.9756, 8-2.4695, 9-3.9512, 10-4.9390, 11-5.9268, 12-7.9024, 13-9.8780 μg.mL^-1) (Purge gas N₂, purge time 300 s, sweep rate 4 mV/s, U. amplitude-100 mV, t. meas 32 ms, t. pulse 35 ms, t. step 2 s, U. step 8 mV, temperature 25°±5°C).

 

Fig.5: Calibration curves for the determination of FLUX using DPPA on DME in the optimum conditions (Ip=Ip,total-Ielect)

Table 2: Determination of flucloxacillin using differential pulse polarographic analysis on DME with negative amplitude in Britton–Robinson (0.04 M) buffer at pH 4.0.

* n=5 t=2.776.

APPLICATIONS:

Many applications for the determination of flucloxacillin in some Syrian pharmaceutical preparations (in presence a same amount of amoxicillin) using differential pulse polarographic analysis on drop mercury electrode with negative amplitude in Britton-Robinson 0.04 M buffer pH 4.0 ^{according to the optimal conditions were proposed. The} amount (m) of FLUX in one capsule was calculated from the following relationship: m=h. m', where: m' is the amount of FLUX in capsule calculated according to the regression equation of calibration curve, h conversion factors are equal to 100 for all pharmaceuticals content 250 mg/cap. The results of quantitative analysis for FLUX in pharmaceutical preparations were summarized in Tables 3. The proposed method was simple, direct and successfully applied to the determination of FLUX in pharmaceuticals without any interference from excipients. Average assay ranged between 99.2 to 102.0%. The results obtained by this method agree well with the contents stated on the labels and were validated by HPLC method [11]. Therefore, the presented method can be recommended for routine analysis of FLUX in pharmaceutical formulations.

 

Method validation:

The developed method for simultaneous estimation of FLUX has been validated in accordance with the International Conference on Harmonization guidelines (ICH) [12].

 

Table 3: Determination of FLUX in some Syrian pharmaceutical preparations using DPPA on DME with negative amplitude in Britton Robinson 0.04 M buffer pH 4.0 according to the optimal condition.

Commercial name	Label Claim of FLUX and AMOX, mg/cap.	*Mean±SD (as FLUX), mg/ cap.	RSD%	Assay %	* (Assay%), by HPLC [11]
Amoxipen capsule, BARAKAT pharmaceutical	250	248.00	2.5	99.2	99.1
Amoxam capsule, IBN HAYYAN	250	250.75	2.4	100.3	100.6
Penifloxam capsule, APHAMEA	250	255.00	2.4	102.0	101.8
Floxin capsule, ALBALSAM pharma	250	249.00	2.5	99.6	99.6
Maxipen capsule, ASIA	250	253.50	2.4	101.4	101.5

*n=5, Assay=(found mean/label claim)x100.

 

Selectivity:

Several other components were examined under the conditions that had been optimized for flucloxacillin determination. The results are seems that amoxicillin and ampicillin did not interfere when present at same amount with flucloxacillin; (The peaks of amoxicillin and ampicillin did not appear within optimum conditions for flucloxacillin determination). While there interfere in the present of cloxacillin because of the difference between E_p components less than 200 mV.

 

Linearity:

Several aliquots of standard stock solution of FLUX were taken in different 25 mL volumetric flasks such that their final concentrations were 0.0494-9.8780 μg.mL^-1 (0.100-20.000 μmol.L^-1) for FLUX using DPPA at DME in Britton Robinson 0.04 M buffer at pH 4.0. Linearity equation obtained was y=-41.952x-0.7611 for the mentioned range (R²=0.9997).

 

Precision and Accuracy:

The precision and accuracy of proposed method was checked by recovery study by addition of standard drug solution to pre-analyzed sample solution at three different concentration levels (80%, 100% and 120%) within the range of linearity for FLUX. The basic concentration level of sample solution selected for spiking of the FLUX standard solution was 3.951 μg.mL^-1. The proposed method was validated statistically and through recovery studies, and was successfully applied for the determination of FLUX in pure and dosage forms with percent recoveries ranged from 99.8% to 101.2%, see Table 4.

 

Table 4: Results of recovery studies

Level	Recovery%
80%	100.3
100%	99.8
120%	101.2

(n=5).

 

Repeatability:

The repeatability was evaluated by performing 10 repeat measurements for 3.951 μg.mL-1of FLUX using the studied DPPA at DME Britton-Robinson 0.04 M buffer pH 4.0 under the optimum conditions. The found amount of FLUX (±SD) was 3.962±0.053 μg.mL-1 and the percentage recovery was found to be 100.3±1.3 with RSD of 0.013. These values indicate that the proposed method has high repeatability for FLUX analysis.

 

Sensitivity (limit of detection [LOD] and limit of quantitation [LOQ]):

The sensitivity of the presented method was evaluated by determining the LOD and LOQ. The values of LOD and LOQ for FLUX are 0.0034 and 0.0102 μg.mL^-1, respectively.

 

 

Robustness:

The robustness of the method adopted is demonstrated by the constancy of the current peak (I_P) with the deliberated minor change in the experimental parameters such as the change in the concentration of excipients, temperature (25±5^oC), pH (4.0±0.20), and C_elect (0.04±10% mol.L^-1) and reaction waiting time (10 min), see Table 5. Indicates the robustness of the proposed method. I_p was measured and assay was calculated for five times.

 

Specificity:

The specificity of the method was ascertained by analyzing standard FLUX in presence of excipients. These findings prove that the suggested methods are specific for determination of the investigated drugs without interference from the coformulated adjuvants.

 

Table5: Robustness of the proposed DPPA method at DME for determination of flucloxacillin.

Experimental parameter variation	Average recovery (%)*
	CFLUX =3.951 μg.mL-1
Temperature 20oC 25oC 30 oC	99.7 100.2 100.4
pH	99.6 99.8
3.8
4.2
CB-R 0.036 mol/L 0.044 mol/L	99.6 100.5
reaction time 10 min 30 min 60 min	99.9 100.4 101.5

* n=5.

 

The homogenization of capsule:

_{The homogenization of capsule in terms of the weight and the amount of drug was studied. It found that the mean weight capsule was 0.6996±0.017 g (i.e.±2.4%), 0.6649±0.013 g (i.e.±1.9%), 0.7051±0.024 g (i.e.±3.4%), 0.6687±0.015 g (i.e.±2.2%) and 0.7116±0.0098 g (i.e.±1.4%) for Amoxipen capsule, Amoxam capsule, Penifloxam capsule, Floxin capsule and Maxipen capsule (250 mg/cap), respectively. And amount of drug in the capsule was 248.00±6.2 mg (i.e.±2.5%), 250.75±5.0 mg (i.e.±2.0%), 255.00±6.1 mg (i.e.±2.4%), 249.00±3.7 mg (i.e.±1.5%) and 253.50±3.1mg (i.e.±1.2%) for Amoxipen capsule, Amoxam capsule, Penifloxam capsule, Floxin capsule and Maxipen capsule (250 mg/cap), respectively; which shows that homogeneity of capsule is acceptable.}

 

Conclusion:

_{Electrochemical behavior and DPPA of FLUX in pure form and in pharmaceutical preparations using DME with Britton Robinson 0.04 M buffer pH 4.0 according to the optimal conditions was applied. One reduction peak was observed. Ip is linear over the range 0.0494-9.8780 μg.mL-1 (0.100-20.000 μmol.L-1). The relative standard deviation did not exceed 2.1% for the concentration 0.0494 μg.mL-1 of FLUX. Regression analysis showed a good correlation coefficient (R2=0.9997) between Ip and concentration over the mentioned range. The proposed method was successfully applied to the direct analysis of FLUX in pharmaceutical formulations without any interference from excipients and with adequate accuracy and sensitivity without any pre-separation such as extraction.}

 

CONFLICT OF INTERESTS:

The authors have declared that no conflict of interests exists.

 

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Accepted on 20.07.2018      © RJPT All right reserved

Research J. Pharm. and Tech 2018; 11(8): 3313-3319.