الفهرس 
part 1Only 14 pages are availabe for public view
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Abstract
The evaluation of sink conditions for Rivaroxiban bulk demonstrated the highest release has been occurred in acetate buffer pH 4.5 with 2 % SLS followed by acetate buffer pH 4.5 then phosphate buffer pH 6.8 and artificial intestinal juice, both of them gave the almost the same results.
In order to evaluate the Rivaroxiban stability in each medium, the acceptable range for solution stability is 98–102%. The stability of the acetate buffer pH 4.5 with 2 % SLS solution prepared for analysis was evaluated for 5 hours (considering the analysis time for routine quality control and dissolution profiles determination). The solution remained stable for the period tested (Fig. 1). So, it was possible to guarantee the integrity of the drug during all the analysis time.
Typical chromatograms of Rivaroxiban reference standard and commercial sample are represented in Fig. 2. The dissolution guidelines cite pH medium, in general, should not be less than 1.2 and do not exceed 8.0, to simulate the physiologic conditions, in this case it was proved the drug required a surfactant to enhance its solubility, 2% of SLS considered accepted as it may simulate the pile salts.
The specificity analysis revealed the HPLC method did not suffer interference by the formulation excipients, since there was not another peak in the retention time of Rivaroxiban (about 7.5 min). The chromatographic peak purity tool, applied for Rivaroxiban peak, demonstrated that it was pure Fig. 3.
The linearity was tested in the concentration range of 4 – 16 mcg/ml . The method demonstrated to be linear, with a correlation coefficient of 0.9999 (Fig. 4).
The slope obtained was 112650.2 and the intercept was 215984.5. The data were validated by means of analysis of variance (ANOVA), which showed significant linear regression and no-significative linearity deviation (P < 0.05)
The stirring speed selection was done based on the range recommended (50–75 rpm) for apparatus 2 [105-106] and as a usual value for tablets dosage form. Since the results obtained using 75 rpm in the preliminary studies were satisfactory, no other speed was tested.
The filters were also evaluated and the 0.45 m membrane was selected. It were demonstrated that no the drug adsorption take place during the process.
The drug release profile obtained in the dissolution test, at the conditions mentioned in Section 2.6,was considered satisfactory (Fig. 4). After 30 min, more than 95% of drug was dissolved in the medium. The values for percentage of Rivaroxiban dissolved per time and the R.S.D. values are in Table 1. The results for R.S.D. were higher for times 10 and 15 min, since the concentration of Rivaroxiban dissolved was small. (See table 21 which show Percentage of rivaroxiban dissolved in the dissolution test).
Once there is only one Rivaroxiban brand in the Egyptian market, it was not done the comparison of dissolution profiles between products.