STUDY OF THE VALIDATION CHARACTERISTICS OF THE METHOD OF QUANTITATIVE DETERMINATION OF URSODEOXYCHOLIC ACID IN SOLID GELATIN CAPSULES WHEN ASSESSING THE UNIFORMITY OF DOSAGE UNITS
DOI:
https://doi.org/10.11603/2312-0967.2024.2.14405Keywords:
ursodeoxycholic acid, uniformity of dosage units, hard gelatin capsules, validation characteristicsAbstract
The aim of the work. To investigate the validation characteristics of the method of quantitative determination of ursodeoxycholic acid (UDCА) in hard gelatin capsules when assessing the uniformity of dosage units (UDU).
Materials and Methods. The UDCA of pharmacopoeial quality produced by "Prodotti Chimici E Alimentari S.p.A.", Italy was used, as well as 6 commercial series of hard gelatin capsules with UDCA of 250 mg from different manufacturers. BPCRS706 produced by Sigma-Aldrich was used as a UDCA standard. For the assay of UDCA, we have developed an analytical HPLC method. The studied validation characteristics are selected in accordance with the requirements of the SFU and ICH recommendations. Determination of UDU was carried out using the calculation-weight method. The content of UDCA in each capsule was calculated based on the results of determining the individual weight and quantitative determination of UDCA by HPLC method.
Results and Discussion. During the validation of the method of quantitative determination UDCA when assessing of the UDU for the control of 250 mg UDCA capsules, it was proven that the specificity, linearity, accuracy, intra-laboratory accuracy, robustness and correctness of the determination are acceptable, the method is not burdened with a systematic error, as systematic error a (-0.152) is insignificant compared to the maximum permissible uncertainty of the analysis (ΔAs ≤ 1.6%). During the control of UDU in hard gelatin capsules it was proven that all studied series of commercial preparations showed acceptable results according to the indicators "Mass Deviation" and "UDU" and had variations in mass deviation below 10% (n = 60), and the average acceptance value (AV) 7.85, which is ≤ 15.
Conclusions. During the validation of the method, statistical processing of the experimental data was carried out, the determined correlation coefficient of linear dependence (r) between the entered and found values for the quantitative content of UDCA is >0.998, which indicates the correctness of the HPLC method for the quantitative content of UDCA when assessing UDU in hard gelatin capsules. According to the results of statistical processing, the method is considered validated and can be used for assay of UDCA. The established conformity of criterion 1 according to the indicator UDU of the commercial series indicates that none of the low-quality series was released to the market, and each patient receives a dose of UDCA within the regulated limits of about 250 mg.
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