Development of composition and evaluation of equivalence of diacerein hard gelatin capsules
Diacerein is a new generation of symptomatic slow-acting agent for the treatment of osteoarthritis, when taken orally, it exhibits moderate anti-inflammatory and analgesic activity, slows down the decay of cartilage tissue and relieves pain and swelling, but its physicochemical properties it is practically insoluble in water, due to which only 35‒56% the drug reaches systemic circulation. Therefore, the search for approaches to increase the dissolution rate of a practically insoluble API using the formulation, type of excipients, degree of solubility and kinetics of the substance release from hard gelatin capsules should provide guaranteed drug efficacy.
The aim of the work is to develop the composition of the drug in the form of hard gelatin capsules based on diacerein, to experimentally study the solubility of diacerein, and to evaluate the composition by studying the kinetics of dissolution of the drug.
Determination of the pH-dependent solubility of diacerein was carried out in the conditions: the volume of the dissolution medium is 250 ml; dissolution temperature 37.0 ± 0.5 ºС. The highest recommended single dose of 50 mg was investigated. The development of the composition of the drug Diacerein, capsules, 50 mg was carried out with the use of various types of excipients and their modifications to achieve the proper technological properties in terms of fluidity (flowability) and a short disintegration time of the capsules for the release of the active substance. Comparative studies of the kinetics of dissolution were carried out by the in vitro method, the test «Dissolution» was studied a «Paddle apparatus» with a rotation speed of 75 rpm, a dissolution medium with a pH value of 1.2, 4.5 and 6.8, in a volume of 900 ml at a temperature of 37 ± 0.5 ºС. The reference drug was used «Artrodarin®», capsules of 50 mg, manufactured by TRB PHARMA S. A.,vArgentina.
It was found that diacerein is practically insoluble in a buffer solution with a pH of 1.2, has a relatively low solubility in a buffer solution with a pH of 4.5, while the solubility of diacerein increases with an increase in the pH of the medium to 6.8. The optimal composition of capsules with diacerein using the wet granulation technology has been developed. The obtained data for bulk density and Carr's index indicate satisfactory flowability of the encapsulating mass. Comparative studies of the dissolution kinetics of the investigational medicinal product and the original drug «Artrodarin®», capsules of 50 mg were carried out. According to the calculations, all the obtained values of the similarity factor are in the range from 50 to 100 and indicate the similarity in buffer media with pH 1.2, 4.5 and 6.8. The developed composition of the preparation is equivalent in dissolution kinetics to the original medicine.
Fishchenko V. O., Kyrychenko V. I., Yaremyn S. Yu. ta in. Osteoartroz kulshovoho suhloba. Klinichni ta sotsialni aspekty zakhvoriuvannia. Analitychnyi ohliad literatury. Chastyna I // Travma. – 2019. – T. 20, № 1. – S. 118–125. https://doi.org/10.22141/1608-1706.1.20.2019.158680
Khyts A. R. Menedzhment bolovoho syndromu v osib pokhyloho viku: fokus na nesteroidni protyzapalni preparaty // Ukr. Med. Chasopys. – 2020. – T. 1, № 6 (140).– XI/XII. ‒ Rezhym dostupu: https://www.umj.com.ua
Supakanya Wongrakpanich, Amaraporn Wongrakpanich, Katie Melhado, Janani Rangaswami. A Comprehensive Review of Non-Steroidal Anti-Inflammatory Drug Use in the Elderly // Aging and Disease. – 2018. – V. 9, N 1. Р. 143–150. https://doi.org/10.14336/AD.2017.0306. PMCID: PMC5772852
Jain S., Nagori B. P., Yadav S. K. Improvement of the Dissolution Behavior of the Poorly Water Soluble Drug Diacerein by Solid Dispersion Technology and its Formulation into Tablet Dosage Form // Madridge J. Novel Drug Res. – 2018. – V. 2, Iss. 1. – Р. 79–89. https://doi.org/10.18689/mjndr-1000112
Kaur D., Kaur J., Kamal S. S. Diacerein, its beneficial impact on chondrocytes and notable new clinical applications // Brazilian J. Pharmac. Sci. – 2019. – V. 54, N 4. – e17534. https://doi.org/10.1590/s2175-97902018000417534
De Oliveira P. G., Termini L., Durigon E. L. et al. Diacerein: A potential multi-target therapeutic drug for COVID-19 // Medical hypotheses. – 2020. – V. 144. – P. 109920. https://doi.org/10.1016/j.mehy. 2020.109920
Baula O. P., Saliy O. O., Bessаrabov V. I., Gerasimchuk A. М. Comparative studies of the kinetics of dissolution of medicines on the basis of clopidogrel // Farmats. zhurn. – 2021. – Т. 76, № 1. – S. 26–34. https://doi.org/10.32352/0367-3057.1.21.03
Chitlange S. S., Pawbake G. R., Pandkar S. V. et al. Formulation and Evaluation of Diacerein Solid Dispersion for Solubility and Dissolution Rate Enhancement // Res. J. Pharmacy and Technol. – 2011. – V. 4, N 6. –P. 932–937.
Kalepu S., Nekkanti V. Insoluble drug delivery strategies: review of recent advances and business prospects // Acta Pharmac. Sinica B. – 2015. – V. 5, Iss. 5. – P. 442–453. https://doi.org/10.1016/j.apsb.2015.07.003
Derzhavnyi reiestr likarskykh zasobiv Ukrainy. – Rezhym dostupu: http://www.drlz.com.ua/
Saliy O. O., Kuryshko H. H., Oherenko Z. O., Getalo O. V. Comparative studies of the release profiles of doxycycline hyclate from solid gelatin capsules when replacing the producers of the active substance // Visn. Kyivskoho nats. un-tu tekhnolohii ta dyzainu. Seriia Tekhnichni nauky. – 2020. – № 3 (146). – S. 165–174. https://doi.org/10.30857/1813-6796.2020.3.14
Diacerein (2409). European Pharmacopoeia. 9th Edition. – European Directorate for the Quality of Medicines (EDQM). – Council of Europe, 67075 Strasbourg Cedex, France 2016. – 4016 p.
Nastanova ST-MOZU 42-7.2:2018 «Likarski zasoby. Doslidzhennia bioekvivalentnosti». – Rezhym dostupu: https://www.dec.gov.ua/wp-content/ uploads/attitude/1.pdf
Derzhavna farmakopeia Ukrainy 2.0 / DP «Ukrainskyi naukovyi farmakopeinyi tsentr yakosti likarskykh zasobiv». 2-e vyd. – Kharkiv: DP «Ukrainskyi naukovyi farmakopeinyi tsentr yakosti likarskykh zasobiv», 2015. – T. 1. – 1128 s.
This work is licensed under a Creative Commons Attribution 4.0 International License.