Development of combined encapsulated drug on the basis of naltrexone and disulfiram

Authors

DOI:

https://doi.org/10.15587/2312-8372.2015.40651

Keywords:

naltrexone, disulfiram, encapsulation, powder for premuscle injection, prolonged action of drugs

Abstract

In the article it is revealed the problem of choice of technology for obtaining the combined drug of prolonged action to ensure continuity of treatment process and relapse prevention of diseases such as drug dependence and alcoholism. In Ukraine and most of the world for the treatment of alcohol and drug dependencies are used disulfiram and naltrexone. In previous studies, the authors have demonstrated promising development of combined injectable drug of prolonged action based on these drugs.

The aim of this study was to obtain the combined injectable drug of prolonged action, which would contain a combination of naltrexone and disulfiram for the treatment of combined alcohol and drug addictions by encapsulation method. The objects of our study served as naltrexone, disulfiram and excipients – copolymers of lactic and glycolic acids with different ratios of elementary units, emulsifiers and solvents.

Analysis of published data allowed us to determine the recommended therapeutic dose of 250 mg of disulfiram and 200 mg of naltrexone. Based on the information, obtained from patents, it is developed the methodology and conducted experiments to obtain encapsulated substances. Size of the emulsion droplets is regulated by rate of stirring: microscale capsules were formed at a speed of 1000 rev/min and nanoscale capsules were formed at speeds over 2,000 rev/min. Capsules were prepared separately from naltrexone and disulfiram in polymers with PLG (50:50) and PLG (70:30) with a ratio of polymer to the drug under 1:2. Morphological characteristics of microcapsules were determined by light microscopy.

The methods of quantitative and qualitative determination of disulfiram in microcapsules are proposed. Prolonging the release of naltrexone is confirmed through test "Dissolution". Also, it is worked fundamental technological scheme of production. Advantages and disadvantages of the proposed technology are determined.

To determine the toxicity and pharmacological activity of obtained microcapsules combined with alcohol and drug addiction it is started preclinical study (Wistar rats and white mice line Balb/c). By the results of this study it will be conducted preliminary comparative analysis of the pharmacological action of drugs Naltetlong and created combined encapsulated drug from naltrexone and disulfiram provided by this technology.

Author Biographies

Володимир Павлович Новіков, Lviv Polytechnic National University, Bandera str. 12, Lviv, Ukraine, 79013

Doctor of Chemical Sciences, Professor

Department of biologically active substances, pharmacy and biotechnology

Наталія Леонідівна Заярнюк, Lviv Polytechnic National University, Bandera str. 12, Lviv, Ukraine, 79013

Candidate of Pharmaceutical Sciences, Associate Professor

Department of biologically active substances, pharmacy and biotechnology

Аеліта Миронівна Кричковська, Lviv Polytechnic National University, Bandera str. 12, Lviv, Ukraine, 79013

Candidate of Pharmaceutical Sciences, Associate Professor

Department of biologically active substances, pharmacy and biotechnology

Олена Валеріївна Федорова, Lviv Polytechnic National University, Bandera str. 12, Lviv, Ukraine, 79013

Candidate of Chemical Sciences, Associate Professor

Department of biologically active substances, pharmacy and biotechnology

Андрій Остапович Милянич, Lviv Polytechnic National University, Bandera str. 12, Lviv, Ukraine, 79013

Candidate of Chemical Sciences, Associate Professor

Department of biologically active substances, pharmacy and biotechnology

References

  1. Egorov, A., Sofronov, A. (2010). Aversivnaia terapiia narkologicheskih zabolevanii: problemy i perspektivy. Nevrologicheskii vestnik, Vol. XLII, № 4, 72-78. Available: http://www.narcom.ru/publ/info/874
  2. Pettinati, H. M., Kampman, K. M., Lynch, K. G., Xie, H., Dackis, C., Rabinowitz, A. R., O′Brien, C. P. (2008, May). A double blind, placebo-controlled trial that combines disulfiram and naltrexone for treating co-occurring cocaine and alcohol dependence. Addictive Behaviors, Vol. 33, № 5, 651–667. doi:10.1016/j.addbeh.2007.11.011
  3. Carroll, K. M., Nich, C., Ball, S. A., Mccance, E., Rounsavile, B. J. (1998, May). Treatment of cocaine and alcohol dependence with psychotherapy and disulfiram. Addiction, Vol. 93, № 5, 713–727. doi:10.1046/j.1360-0443.1998.9357137.x
  4. Malcolm, R., Olive, M. F., Lechner, W. (2008, July). The safety of disulfiram for the treatment of alcohol and cocaine dependence in randomized clinical trials: guidance for clinical practice. Expert Opinion on Drug Safety, Vol. 7, № 4, 459–472. doi:10.1517/14740338.7.4.459
  5. Mutschler, J., Diehl, A., Kiefer, F. (2008, April). Klinische Pharmakologie von Disulfiram - eine aktuelle Übersicht. Fortschritte der Neurologie · Psychiatrie, Vol. 76, № 4, 225–231. doi:10.1055/s-2007-1016438
  6. Petrakis, I. L., Poling, J., Levinson, C., Nich, C., Carroll, K., Rounsaville, B. (2005, May). Naltrexone and Disulfiram in Patients with Alcohol Dependence and Comorbid Psychiatric Disorders. Biological Psychiatry, Vol. 57, № 10, 1128–1137. doi:10.1016/j.biopsych.2005.02.016
  7. Petrakis, I. L., Carroll, K. M., Nich, C., Gordon, L. T., McCance-Katz, E. F., Frankforter, T., Rounsaville, B. J. (2000, February). Disulfiram treatment for cocaine dependence in methadone-maintained opioid addicts. Addiction, Vol. 95, № 2, 219–228. doi:10.1046/j.1360-0443.2000.9522198.x
  8. Mutschler, J., Diehl, A., Volmert, С. et al. (2008). Recent results in relaps prevention of alcoholism with Disulfiram. Neuropsychiatrie, Vol. 22, № 4, 243–251.
  9. Oslin, D. W., Pettinati, H. M., Volpicelli, J. R., Wolf, A. L., Kampman, K. M., O’Brien, C. P. (1999, March). The Effects of Naltrexone on Alcohol and Cocaine Use in Dually Addicted Patients. Journal of Substance Abuse Treatment, Vol. 16, № 2, 163–167. doi:10.1016/s0740-5472(98)00039-7
  10. Suh, J. J., Pettinati, H. M., Kampman, K. M., O’Brien, C. P. (2006). The Status of Disulfiram. Journal of Clinical Psychopharmacology, Vol. 26, № 3, 290–302. doi:10.1097/01.jcp.0000222512.25649.08
  11. Zagoriy, G., Zayarnyuk, N., Sobetov, B., Krychkovska, A. et al. (2013). Development of the Optimal Composition and the Technology of New Combined Injectable Drug with Prolonged Action Based on Disulfiram and Naltrexone. Research Journal of Pharmaceutical, Biological and Chemical Sciences, Vol. 4, № 2, 221–227.
  12. Derzhavne pidpryiemstvo «Naukovo-eksperymentalnyi farmakopeinyi tsentr». (2001). Derzhavna farmakopeia Ukrainy. Ed. 1. Kh.: RIREH, 532.
  13. Alekseev, K. V., Gritskova, I. A., Kedik, S. A. (2011). Polimery dlia farmatsevticheskoi tehnologii. M., 511.
  14. Tice, T. R., Staas, J. K., Ferrel, T. M. (23.10.2001). Pat. USA № 606425. Primary class 426/426. Injectable naltrexone microsphere compositions and their use in reducing consumption of heroin and alcohol. № 545064; filing date 07.04.2000.
  15. Zayarnyuk, N. L., Lunin, V. V., Fedorova, O. V. et al. (2014). Rozrobka inkapsulovanoho likarskoho zasobu na osnovi naltreksonu ta dysulfiramu. Visnyk NU “LP”. Khimiia, tekhnolohiia rechovyn ta yikh zastosuvannia, 787, 235-238.
  16. Derzhavne pidpryiemstvo «Naukovo-eksperymentalnyi farmakopeinyi tsentr». (2008). Derzhavna farmakopeia Ukrainy. Ed. 1. Supplement. Kh.: RIREH, 620.
  17. Sydorov, Yu. I., Chuieshov, V. I., Novikov, V. P. (2009). Protsesy i aparaty khimiko-farmatsevtychnoi promyslovosti. Vinnytsia: Nova knyha, 816.

Downloads

Published

2015-04-02

How to Cite

Новіков, В. П., Заярнюк, Н. Л., Кричковська, А. М., Федорова, О. В., & Милянич, А. О. (2015). Development of combined encapsulated drug on the basis of naltrexone and disulfiram. Technology Audit and Production Reserves, 2(4(22), 71–75. https://doi.org/10.15587/2312-8372.2015.40651

Issue

Vol. 2 No. 4(22) (2015): Technologies of food, light and chemical industry

Section

Technologies of food, light and chemical industry

License

Copyright (c) 2016 Володимир Павлович Новіков, Наталія Леонідівна Заярнюк, Аеліта Миронівна Кричковська, Олена Валеріївна Федорова, Андрій Остапович Милянич

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

The consolidation and conditions for the transfer of copyright (identification of authorship) is carried out in the License Agreement. In particular, the authors reserve the right to the authorship of their manuscript and transfer the first publication of this work to the journal under the terms of the Creative Commons CC BY license. At the same time, they have the right to conclude on their own additional agreements concerning the non-exclusive distribution of the work in the form in which it was published by this journal, but provided that the link to the first publication of the article in this journal is preserved.