COMPARATIVE STUDIES OF THE RELEASE PROFILES OF DOXYCYCLINE HYCLATE FROM SOLID GELATIN CAPSULES WHEN REPLACING THE PRODUCERS OF THE ACTIVE SUBSTANCE

Abstract

Comparative studies of the release profiles of doxycycline hyclate from hard gelatine capsules, developed with the active ingredient of alternative manufacturers. The object of the study is samples of the drug doxycycline hyclate in the form of hard gelatin capsules made from an API of an approved manufacturer "Kaifeng Pharmaceutical Group Co. Ltd", China and an alternative manufacturer "Hebei Jiupeng Pharmaceutical Co., Ltd.", China. The study of the profiles of the release of the active substance from the drug was carried out using the "Paddle apparatus". The amount of the released substance was determined by the absorption spectrophotometry method.A drug was investigated in hard gelatin capsules of 100 mg based on the substance of doxycycline hyclate from two manufacturers "Kaifeng Pharmaceutical Group Co. Ltd", China, and "Hebei Jiupeng Pharmaceutical Co., Ltd", China. It was found that according to the profile of impurities and the results of quality indicators, the substances of doxycycline hyclate from the studied manufacturers are alternative and interchangeable. To confirm the similarity of the dissolution profiles of doxycycline, 100 mg capsules were tested in accordance with the requirements of the State Pharmacopoeia Department, 2.9.3. Dissolution test, using solutions at three pH values: pH 1.0 (0.1 M HCl), pH 4.6 (acetate buffer) and pH 6.8 (phosphate physiological buffer). Comparative studies in vitro for two batches of the medicinal product established the similarity of the kinetics of the release of the active substance. The calculated values of the similarity factor are: f2 = 78.4 for a solution with pH = 1.2; f2 = 82.7 for a solution with pH = 4.6 and f2 = 75.8 for a solution with pH = 6.8. According to studies in three buffer solutions, the similarity coefficient is in the range from 50 to 100, which allows it to conclude that the studied API manufacturers can be used as alternatives for the production of the drug doxycycline hyclate in hard gelatin capsules of 100 mg. The relative standard deviation of the mean (RSD) release rate is less than 20% at the first control point and not more than 10% from the second to the last control point, indicating that the results are valid. It has been proven that the study of the dissolution profiles of solid dosage forms in vitro makes it possible to assess the risks of using APIs synthesized by various manufacturers. The obtained results of the experiment allow manufacturers of finished medicines to reasonably use alternative manufacturers of raw materials to ensure uninterrupted industrial production and meet market demand.