Development of the composition and research of the equivalence of suppositories with diclofenac sodium by in vitro method using “Dissolution” test for lipophilic solid dosage forms

Authors

  • O. O. Salii Kyiv National University of Technologies and Design, Ukraine,
  • O. P. Baula Kyiv National University of Technologies and Design, Ukraine,
  • А. I. Kharytonenko Kyiv National University of Technologies and Design, Ukraine,
  • L. A. Fukleva Zaporizhzhіa State Medical University, Ukraine,
  • A. S. Kyryliuk Kyiv National University of Technologies and Design, Kyiv, Ukraine,

DOI:

https://doi.org/10.14739/2310-1210.2019.2.161511

Keywords:

diclofenac sodium, suppositories, dissolution, flow-through cell

Abstract

The aim: Development of the composition and investigation of the equivalence of suppositories with sodium diclofenac by in vitro method on a device with a flow-through cell in accordance with modern requirements of SPhU.

Materials and methods: The development of the suppository composition was carried out with the use of the substance of diclofenac sodium and the excipient of solid fat of various grades. Studies of the active ingredient release in vitro in comparison with the reference listed drug were carried out on a device with a flow-through cell according to the monograph SPhU 2.9.42.

Results: The investigations of the physical-chemical properties of the diclofenac sodium substance (micronisation, solubility) and the basis of the solid fat carrier, which affect the release of the active ingredient from the drug formulation were carried. The "particle size" figure for 2 samples of the active ingredient was from 100 μm to 400 μm and not more than 15 μm, respectively. The optimal composition of suppositories was developed by the method of 2-factor experiments. The conditions for the "Dissolution" test were determined: the volume of the medium (720 ml), the dissolution temperature (37.0 ± 0.5) ºC, the time taken for sampling (15, 30, 45, 60, 90 min), the dissolution medium – buffered solution with a pH of 7.4. The calculated similarity factor f2 was 67, which indicates the similarity of the release profiles and the equivalence of the researched drug.

Conclusions The pharmaco-technological properties of sodium diclofenac and the solid fat auxiliary substance were studied. A method for the release of sodium diclofenac with the use of a device with a flow-through cell in accordance with the requirements of the SPhU is developed. The level of release of sodium diclofenac in the dissolution medium from rectal suppositories was determined by the experimental method, as the first step in the bioavailability determination. The equivalence of the tested samples of suppositories with the reference listed drug with the help of the method in vitro was established.

References

Stefanov, O. V. (Ed) (2001). Doklinichni doslidzhennia likarskykh zasobiv [Preclinical studies of medicinal products: methodical recommendations]. Kyiv: Avicena. [in Ukrainian].

Derzhаvnyi reiestr likarskykh zasobiv Ukrainy [State Register of Drugs of Ukraine]. Retrieved from http://www.drlz.kiev.ua [in Ukrainian].

Al Zedan, Fadi, Gladysheva, S. A., & Burlaka, B. S. (2011). Issledovanie granulometricheskogo sostava amlodipina i ego vliyaniya na biofarmacevticheskie svojstva rektal'nykh supozytoriev [Investigation of the granulometric size composition of amlodipine and its influence on the biopharmaceutical properties of rectal suppositories]. Zaporozhye medical journal, 13(6), 110–112. [in Russian].

Fukleva, L. A., Puchkan, L. O., & Biruk, I. А. (2017). Aktualnіst rozrobky miahkoi likarskoi formy іz efіrnoi olіi chabretsiu zvychainoho dliа profіlaktiky hіnekolohіchnykh zakhvoriiuvan [Actuality of the development of semi-solid with etheroleum of Thymus vulgaris L. for the prophylaxis of gynecological disorders]. Suchasnі medychnі tekhnolohii, 2(33), 56–60. [in Ukrainian].

Krowczynski, L., & Krasowaka, H. (1975). Metody analitychzne stosowane w badaniach biofarmaceutycznych. Biul. Inform. Inst. przem. pharm., 23(3), 284–293.

Hargoli, S., Farid, J., Azarmi, S. H., Ghanbarzadeh, S., & Zakeri-Milani, P. (2013). Preparation and In vitro Evaluation of Naproxen Suppositories. Indian J Pharm Sci., 75(2), 143–148. doi: 10.4103/0250-474X.115458

Pugunes, S., & Ugandar, R. E. (2013). Formulation and evaluation of natural palm oil based diclofenac sodium, suppositories. IJPSR, 4(2), 617–621.

Nicoară, A. C., Cazacincu, R., Lupeasa, D., Miron, D. S., & Rădulescu, F. Ș. (2015). Formulation and in vitro release testing of rectal suppositories containing nimesulide. Farmacia, 1(63), 111–117.

Derzhavne pidpryiemstvo «Ukrainskyi naukovyi farmakopeinyi tsentr yakosti likarskykh zasobiv» (2015). Derzhavna Farmakopeia Ukrainy [State Pharmacopoeia of Ukraine], (Vol. 1). Kharkiv. [in Ukrainian].

Loyd, V. A., Worthen, D. B., & Mink, Bill. (2008) Suppositories. Pharmaceutical Press.

DP «Derzhavnyi ekspertnyi tsentr Ministerstvo okhorony zdorovia Ukrainy» (2016) Doslіdzhennia bіoekvіvalentnostі. ST-N MOZU 42-7.1:2016 [The Investigation of Bioequivalence]. [in Ukrainian].

Nainar, S., Rajiah, K., Angamuthu, S., Prabakaran, D., & Kasibhatta, R. (2012). Biopharmaceutical Classification System in Invitro/In-vivo Correlation: Concept and Development Strategies in Drug Delivery. Tropical Journal of Pharmaceutical Research, 11(2), 319–329. doi: 10.4314/tjpr.v11i2.20.

Tencova, A. I., Groshovyi, T. A., Golovkin, V. A., & Makhkamov, S. M. (1980). Metodicheskie ukazaniya po obrabotke rezul'tatov e'ksperimenta po tekhnologii lekarstv [Methodical instructions for processing the results of the experiment on the technology of drugs]. Tashkent. [in Russian].

Salіi, O. O., Kuzmіna, H. І., & Bovgyria, І. M. (2017). Standartyzatsіia testu «Rozchynennia» dlia tverdykh dozovanykh form u formі supozytorіiv [Standardization of the «Dissolution» test for solid dosage forms in the form of suppositories]. Tekhnolohіchnі ta bіofarmacevtychnі aspekty stvorennia lіkarskykh preparatіv rіznoi napravlenostі dіi Proceedings of the 3rd International Scientific and Practical Internet Conference (pp. 171–172). Kharkіv. [in Ukrainian].

Lawrence, X. Yu., & Bing, V. Li. (2014). FDA Bioequivalence Standards. Springer.

WHO Technical Report Series 937, Annex 7 Multisource (generic) pharmaceutical products: guidelines on registration requirements to establish interchagebility. Retrieved from http://www.who.int/medicines/areas/quality_safety/quality_ assurance / Annex7-TRS992.pdf.

Downloads

How to Cite

1.
Salii OO, Baula OP, Kharytonenko АI, Fukleva LA, Kyryliuk AS. Development of the composition and research of the equivalence of suppositories with diclofenac sodium by in vitro method using “Dissolution” test for lipophilic solid dosage forms. Zaporozhye Medical Journal [Internet]. 2019Apr.2 [cited 2024Nov.27];(2). Available from: http://zmj.zsmu.edu.ua/article/view/161511

Issue

No. 2 (2019)

Section

Original research

License

Authors who publish with this journal agree to the following terms:

    1. Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.  Лицензия Creative Commons
    2. Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
    3. Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access)