Просмотр новости
Найдите то, что Вас интересует
Спутники
РН
SpaceX
Роскосмос
NASA
СпутникиРНSpaceXРоскосмосNASABackground. One way to improve existing oral medications whose active pharmaceutical ingredient (API) is primarily absorbed in the stomach or upper small intestine is to develop floating modified-release dosage forms (DFs). Sitagliptin, a hypoglycemic drug from the dipeptidylpetidase-4 inhibitor group used in the treatment of type 2 diabetes, possesses these properties. Therefore, the development of floating sitagliptin capsules is relevant.Objective. Development and optimization of the composition and technology of sitagliptin floating capsules with a given release profile — release of more than 90 % of the API within 6 h, compliance with zero-order kinetics, as well as special properties — “total floating time” — 6 h and minimal “floating lag time”.Materials and methods. The study examined floating capsules containing the sitagliptin API. The capsule mass was produced by wet granulation, and the dosing method mimicked the operation of machines that compacted the powder and then placed it into the capsule shell. The experimental design was based on the surface response method with a central composite design, regression and variance analysis, and optimization using generalized desirability. Release profiles were studied in a 0.1 M hydrochloric acid solution using a Dissolution Tester and UV spectrophotometry.Results. As a result of optimization, the values of critical formulation attributes and process parameters for obtaining floating capsules of sitagliptin were established: the proportion of floating agent-matrix former in the total mass of matrix-forming polymers is 51.35 % (the proportion in the composition is 24.44 %) and the compaction force of the capsule mass — 1.90 kN, at which the DFs demonstrated a total release of 99.22±0.44 %, compliance of the dissolution kinetics with the zero-order model (R2 = 0.9764), “floating lag time” — 15.79±2.53 s and “total floating time” — more than 6 h.Conclusions. During the study, the composition and technology of sitagliptin floating capsules with controlled release of the API, corresponding to zero-order kinetics, and 6-hour flotation were developed, based on the concept of “air incorporation during pressing or compaction of the mixture” using wet granulation with dosing into the shell using the “Piston-Tamp” principle. The resulting DFs potentially increase the absorption of the API and reduce the spike in plasma concentrations.
1. Omidian H. Gastroretentive drug delivery systems: A holy grail in oral delivery. Drug Discov Today. 2025 Apr;30(4):104340. doi: 10.1016/j.drudis.2025.104340.
2. Blynskaya EV, Vinogradov VP, Tishkov SV, et al. Modern Approaches to Obtaining Floating Drug Dosage Forms (A Review). Pharm Chem J. 2022;56:1277–84. doi: 10.1007/s11094-022-02786-w.
3. Дедов И.И., Шестакова М.В., Викулова О.К. и др. Эпидемиологические характеристики сахарного диабета в Российской Федерации: клинико-статистический анализ по данным Федерального регистра сахарного диабета на 01.01.2021. Сахарный диабет. 2021;24(3):204-221. doi: 10.14341/DM12759.
4. Петунина Н.А., Гончарова Е.В., Тельнова М.Э. и др. Ситаглиптин – первый в мире ингибитор ДПП-4. Медицинский совет. 2019;4:14-19. doi: 10.21518/2079-701X-2019-4-14-19.
5. Scott LJ. Sitagliptin: A Review in Type 2 Diabetes. Drugs. 2017 Feb;77(2):209-224. doi: 10.1007/s40265-016-0686-9.
6. Сидоров А.В. Клиническая фармакология ингибиторов дипептидилпептидазы 4: сравнительный обзор. Эффективная фармакотерапия. 2020;16(25):24-48. doi: 10.33978/2307-3586-2020-16-25-24-48.
7. Gumieniczek A, Berecka A, Mroczek T, et al. Determination of chemical stability of sitagliptin by LC-UV, LC-MS and FT-IR methods. J Pharm Biomed Anal. 2019 Feb 5;164:789-807. doi: 10.1016/j.jpba.2018.11.023.
8. Виноградов В.П., Тишков С.В., Блынская Е.В., Алексеев К.В. Перспективные нелипидные флотирующие агенты для технологии гастроретентивных систем доставки лекарственных средств. Экспериментальная и клиническая фармакология. 2023;86(11S):28. doi: 10.30906/ekf-2023-86s-28.
9. Виноградов В.П., Маркеев В.Б., Тишков С.В. и др. Потенциальные вспомогательные вещества в технологии пористых плавающих таблеток и капсул. Известия ГГТУ. Медицина, фармация. 2024;2:78-84. doi: 10.51620/2687-1521-2024-2-18-78-84.
10. Schneider F, Koziolek M, Weitschies W. In Vitro and In Vivo Test Methods for the Evaluation of Gastroretentive Dosage Forms. Pharmaceutics. 2019 Aug 16;11(8):416. doi: 10.3390/pharmaceutics11080416.
11. Филиппова Н.И., Теслев А.А. Применение математического моделирования при оценке высвобождения лекарственных веществ in vitro. Разработка и регистрация лекарственных средств. 2017;(4):218- 226.
12. Mirani AG, Patankar SP, Kadam VJ. Risk-based approach for systematic development of gastroretentive drug delivery system. Drug Deliv Transl Res. 2016 Oct;6(5):579-96. doi: 10.1007/s13346-016-0315-x.
13. Sethi S, Mangla B, Kamboj S, Rana V. A QbD approach for the fabrication of immediate and prolong buoyant cinnarizine tablet using polyacrylamide-g-corn fibre gum. Int J Biol Macromol. 2018 Oct 1;117:350- 361. doi: 10.1016/j.ijbiomac.2018.05.178.
14. Ha JM, Seo JW, Kim SH, et al. Implementation of Quality by Design for Formulation of Rebamipide Gastro-retentive Tablet. AAPS PharmSciTech. 2017 Nov;18(8):3129-3139. doi: 10.1208/s12249-017-0797-y.
15. Singh B, Kaur A, Dhiman S, et al. QbD-Enabled Development of Novel Stimuli-Responsive Gastroretentive Systems of Acyclovir for Improved Patient Compliance and Biopharmaceutical Performance. AAPS PharmSciTech. 2016 Apr;17(2):454-65. doi: 10.1208/s12249-015-0367-0.
16. Bansal S, Beg S, Garg B, et al. QbD-Oriented Development and Characterization of Effervescent Floating-Bioadhesive Tablets of Cefuroxime Axetil. AAPS PharmSciTech. 2016 Oct;17(5):1086-99. doi: 10.1208/s12249-015-0431-9.