Stability of Nitrofurantoin in Extemporaneously Compounded Suspensions: RESULTS

stability

Regression analysis of the peak area ratio of nitrofurantoin to internal standard versus concentration demonstrated linearity over the working range of the concentrations, with coefficients of determination (r2) greater than 0.999 (n = 4). The intraday (n = 4) and interday (n = 4) coefficients of variation for the 3 different concentrations were within acceptable limits: 0.06% and 0.30%, respectively, for the 0.25 mg/mL suspension; 0.06% and 0.13%, respectively, for the 1.00 mg/mL suspension; and 0.20% and 0.09%, respectively, for the 2.00 mg/mL suspension.

When nitrofurantoin was subjected to degradation, there was no noticeable change in its peak shape. An apparent degradation product eluted at 4.3 min and was well separated from the nitrofurantoin such that the decline in the nitrofurantoin concentration could be easily detected (Figure 1). Thus, the HPLC method was deemed capable of indicating stability.
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Table 1. Mean Nitrofurantoin Concentration + Standard Deviation (and Mean Percentage Remaining*) during 91 Days of Storage at 4°C and 25°Ct


Study Dayt


4°C


25°C



Day


0


0.861 ± 0.034


0.859 ± 0.045



Day


7



0.804


±


0.115


(93.4)


0.788 ± 0.052


(91.7)



Day


14



0.862


±


0.118


(100.1)


0.861 ± 0.056


(100.2)



Day


21



0.847


±


0.178


(98.4)



0.904


±


0.043


(105.2)


Day 28



0.956 ±


0.041


(111.0)


0.815 ±0.212


(94.9)



Day


35


0.787 ± 0.057


(91.4)


0.868 ± 0.063


(101.0)



Day


42



0.939 ±


0.047


(109.1)


0.888 ± 0.071


(103.4)



Day


49


0.855 ± 0.023


(99.3)


0.792 ± 0.009


(92.2)


Day 56


0.856 ± 0.052


(99.4)



0.847


±


0.126


(98.6)



Day


63


0.859 ± 0.074


(99.8)


0.785 ± 0.074


(91.4)


Day 70



0.877 ±


0.043


(101.9)


0.794 ±0.129


(92.4)


Day 77


0.891 ± 0.023


(103.5)


0.810 ±0.045


(94.3)



Day


91



0.842


±


0.106


(97.8)


0.894 ±0.119


(104.1)



%


remaining on day


91


by linear regression§


99.43


98


.58



Lower limit of


95%


CI for


%


remaining||


93.13


92.63



CI


=


confidence interval.



*Percentage remaining was calculated in relation to the initial concentration (day
0).

tNominal initial concentration: l.00 mg/mL.


Ф№
determinations were made on day 84 (12 weeks).


§Calculated from concentration on day
91

as determined by linear regression and concentration observed on day
0,

according to the following formula: concentration on day
91/concentration on day
0 x 100.

IICalculated from lower limit of
95%

CI of the slope of the curve relating concentration to time, determined
by linear regression, according to the following formula: lower limit of


95%
CI of concentration on day 91/concentration on day

0
x 100.

No notable changes in physical appearance, odour, colour, or taste of the suspensions occurred over the first 14 days of the study period. Each cloudy yellow suspension had a faint sweet smell and taste. Afterward, a very slight change in taste (more bitter) and smell (less sweet) occurred, and these characteristics remained stable until the end of the study. The suspensions appeared to maintain constant viscosity (based on visual inspection only, not on measurements with a viscometer) and were easily resuspended throughout the study period. Furthermore, only minimal fluctuations of pH were observed. The mean pH (± standard deviation) was 4.45 ±0.10 when the suspension was stored at 4°C and 4.41 ± 0.12 when stored at 25°C.
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Figure 1. Upper panel

Figure 1. Upper panel: Chromatogram showing nitrofurantoin peak at 5.3 min and peak for the internal standard (IS), furazolidone, at 6.2 min. Lower panel: Chromatogram of the degradation study showing peak for presumed degradation product at 4.3 min and nitrofurantoin (26.5% remaining) and IS peaks.

The retention time for nitrofurantoin was 5.3 min, whereas the retention time for the internal standard, furazolidone, was 6.2 min (Figure 1). The HPLC analysis showed that at both storage temperatures, the 10 mg/mL suspensions maintained at least 90% of their initial concentrations on every study day (Table 1). Further­more, more than 98% of the initial nitrofurantoin concentration remained on day 91, according to linear regression analysis of the concentration-time data. The lower limit of the 95% CI also indicated that more than 92% of the initial concentration remained on day 91 (Table 1). Viagra Super Active

Category: Main

Tags: nitrofurantoin, stability, suspension

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