pharmjournalРазработка и регистрация лекарственных средствDrug development & registration2305-20662658-5049LLC «CPHA»pharmjournal-635Research ArticleФАРМАЦЕВТИЧЕСКАЯ ТЕХНОЛОГИЯPHARMACEUTICAL TECHNOLOGYОБОСНОВАНИЕ ВЫБОРА ВСПОМОГАТЕЛЬНЫХ КОМПОНЕНТОВ НАЗАЛЬНОГО СПРЕЯ НАЛТРЕКСОНА ГИДРОХЛОРИДАRATIONALE FOR THE SELECTION OF AUXILIARY COMPONENTS FOR THE NALTREXONE HYDROCHLORIDE NASAL SPRAYДомнинаЮ. М.DomninaY. M.noemail@neicon.ruКедикС. А.KedikS. A.noemail@neicon.ruСусловВ. В.SuslovV. V.noemail@neicon.ruШнякЕ. А.ShnyakE. A.noemail@neicon.ru«МИРЭА - Российский технологический университет»; АО «Институт фармацевтических технологий»«MIREA - Russian Technological University»; Institute of pharmaceutical technologies201809012019047377Copyright © Домнина Ю.М., Кедик С.А., Суслов В.В., Шняк Е.А., 20192019Домнина Ю.М., Кедик С.А., Суслов В.В., Шняк Е.А.Domnina Y.M., Kedik S.A., Suslov V.V., Shnyak E.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.pharmjournal.ru/jour/article/view/635

Работа посвящена созданию назального спрея налтрексона гидрохлорида. Налтрексон в дозах 3-5 мг/сут воздействует на опиоидный рецептор фактора роста (OGFr) и толл-подобный рецептор 4, что делает его перспективным средством для применения в комплексной терапии аутоиммунных заболеваний и состояний, вызванных ослабленным иммунитетом. Для предотвращения вытекания препарата из полости носа в его состав был введен термочувствительный полоксамер Kolliphor® Р 407. Изучена динамическая вязкость модельных образцов в диапазоне температур 7-37 °С. Исследована скорость диализа и степень высвобождения налтрексона. Подобран оптимальный состав для создания комфортного в применении препарата «Налтрексона гидрохлорид, спрей назальный», 25 мг/мл.

The work is devoted to the development of nasal spray containing naltrexone hydrochloride. Naltrexone in doses of 3-5 mg/day acts on the opioid growth factor receptor (OGFr) and toll-like receptor 4 that makes it promising for use in the complex therapy of autoimmune diseases and conditions caused by impaired immunity. To prevent leakage of the drug from the nasal cavity, the thermosensitive poloxamer (Kolliphor® P 407) was introduced into its composition. The dynamic viscosity was studied of model samples in the temperature range of 7-37 °C. The rate of dialysis and the degree of release was investigated of naltrexone. Selected the optimal composition to create a comfortable to use drug «Naltrexone hydrochloride, nasal spray», 25 mg/ml.

налтрексона гидрохлориднизкие дозы налтрексонаназальный спрейполимерывязкостьnaltrexone hydrochloridelow dose naltrexonenasal spraypolymersviscosityReferencesResnick R. B. et al. Studies of EN-1639A (naltrexone): a new narcotic antagonist // American Journal of Psychiatry. 1974. V. 131. № 6. С. 646-650.Resnick R. B. et al. Studies of EN-1639A (naltrexone): a new narcotic antagonist // American Journal of Psychiatry. 1974. V. 131. № 6. С. 646-650.Patten D. K., Schultz B. G., Berlau D. J. The Safety and Efficacy of Low-Dose Naltrexone in the Management of Chronic Pain and Inflammation in Multiple Sclerosis, Fibromyalgia, Crohn’s Disease, and Other Chronic Pain Disorders // Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy. 2018. V. 38. № 3. С. 382-389.Patten D. K., Schultz B. G., Berlau D. J. The Safety and Efficacy of Low-Dose Naltrexone in the Management of Chronic Pain and Inflammation in Multiple Sclerosis, Fibromyalgia, Crohn’s Disease, and Other Chronic Pain Disorders // Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy. 2018. V. 38. № 3. С. 382-389.Elsegood L. The LDN Book: How a Little-Known Generic Drug - Low Dose Naltrexone - Could Revolutionize Treatment for Autoimmune Diseases, Cancer, Autism, Depression, and More. - Chelsea Green Publishing, 2016.Elsegood L. The LDN Book: How a Little-Known Generic Drug - Low Dose Naltrexone - Could Revolutionize Treatment for Autoimmune Diseases, Cancer, Autism, Depression, and More. - Chelsea Green Publishing, 2016.Ringerike T., Pike E., Nevjar J., Klemp M. NIPH systematic reviews: executive summaries, The Use of Naltrexone in Low Doses Beyond the Approved Indication, Knowledge Centre for the Health Services at The Norwegian Institute of Public Health (NIPH) Copyright (c)2015 by The Norwegian Institute of Public Health (NIPH). Oslo, Norway, 2015.Ringerike T., Pike E., Nevjar J., Klemp M. NIPH systematic reviews: executive summaries, The Use of Naltrexone in Low Doses Beyond the Approved Indication, Knowledge Centre for the Health Services at The Norwegian Institute of Public Health (NIPH) Copyright (c)2015 by The Norwegian Institute of Public Health (NIPH). Oslo, Norway, 2015.Brown N., Panksepp J. Low-dose naltrexone for disease prevention and quality of life, Med. Hypotheses. 2009. V. 72. P. 333-337.Brown N., Panksepp J. Low-dose naltrexone for disease prevention and quality of life, Med. Hypotheses. 2009. V. 72. P. 333-337.Donahue R. N., McLaughlin P. J., Zagon I. S. Low-dose naltrexone suppresses ovarian cancer and exhibits enhanced inhibition in combination with cisplatin, Exp. Biol. Med. (Maywood, NJ). 2011. V. 236 P. 883-895.Donahue R. N., McLaughlin P. J., Zagon I. S. Low-dose naltrexone suppresses ovarian cancer and exhibits enhanced inhibition in combination with cisplatin, Exp. Biol. Med. (Maywood, NJ). 2011. V. 236 P. 883-895.Dodou K., Armstrong A., Kelly I., Wilkinson S., Carr K., Shattock P. et al. Ex vivo studies for the passive transdermal delivery of low-dose naltrexone from a cream; detection of naltrexone and its active metabolite, 6beta-naltrexol, using a novel LC Q-ToF MS assay, Pharm. Dev. Technol. 2015. V. 20. P. 694-701.Dodou K., Armstrong A., Kelly I., Wilkinson S., Carr K., Shattock P. et al. Ex vivo studies for the passive transdermal delivery of low-dose naltrexone from a cream; detection of naltrexone and its active metabolite, 6beta-naltrexol, using a novel LC Q-ToF MS assay, Pharm. Dev. Technol. 2015. V. 20. P. 694-701.Данилов А. Б. Фибромиалгия: новые возможности терапии // РМЖ. 2010. Т. 18. № 16. С. 998-1003.Danilov A. B. Fibromyalgia: new treatment options // RMJ. 2010. V. 18. № 16. P. 998-1003.Ramanathan S., Panksepp J., Johnson B. Is fibromyalgia an endocrine / endorphin deficit disorder? Is low dose naltrexone a new treatment option? // Psychosomatics. 2012. V. 53. № 6. С. 591-594.Ramanathan S., Panksepp J., Johnson B. Is fibromyalgia an endocrine / endorphin deficit disorder? Is low dose naltrexone a new treatment option? // Psychosomatics. 2012. V. 53. № 6. С. 591-594.Smith J. P. et al. Low-dose naltrexone therapy improves active Crohn’s disease //The American journal of gastroenterology. 2007. V. 102. № 4. С. 820.Smith J. P. et al. Low-dose naltrexone therapy improves active Crohn’s disease //The American journal of gastroenterology. 2007. V. 102. № 4. С. 820.Parker C. E. et al. Low dose naltrexone for induction of remission in Crohn’s disease //The Cochrane database of systematic reviews. 2018. V. 4. P. 10-25.Parker C. E. et al. Low dose naltrexone for induction of remission in Crohn’s disease //The Cochrane database of systematic reviews. 2018. V. 4. P. 10-25.Agrawal Y. P. Low dose naltrexone therapy in multiple sclerosis // Medical hypotheses. 2005. V. 64. № 4. С. 721-724.Agrawal Y. P. Low dose naltrexone therapy in multiple sclerosis // Medical hypotheses. 2005. V. 64. № 4. С. 721-724.Yi Z. et al. Functional modulation on macrophage by low dose naltrexone (LDN) //International immunopharmacology. 2016. V. 39. С. 397-402.Yi Z. et al. Functional modulation on macrophage by low dose naltrexone (LDN) //International immunopharmacology. 2016. V. 39. С. 397-402.Liu W. M. et al. Naltrexone at low doses upregulates a unique gene expression not seen with normal doses: Implications for its use in cancer therapy//International journal of oncology. 2016. V. 49. № 2. С. 793-802.Liu W. M. et al. Naltrexone at low doses upregulates a unique gene expression not seen with normal doses: Implications for its use in cancer therapy//International journal of oncology. 2016. V. 49. № 2. С. 793-802.Li Z. et al. Low-dose naltrexone (LDN): A promising treatment in immune-related diseases and cancer therapy//International immunopharmacology. 2018. V. 61. С. 178-184.Li Z. et al. Low-dose naltrexone (LDN): A promising treatment in immune-related diseases and cancer therapy//International immunopharmacology. 2018. V. 61. С. 178-184.Younger J., Parkitny L., McLain D. The use of low-dose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic pain //Clinical rheumatology. 2014. Т. 33. № 4. С. 451-459.Younger J., Parkitny L., McLain D. The use of low-dose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic pain //Clinical rheumatology. 2014. Т. 33. № 4. С. 451-459.Skulberg A. K. et al. Pharmacokinetics and-dynamics of intramuscular and intranasal naloxone: an explorative study in healthy volunteers// European journal of clinical pharmacology. 2018. С. 1-11.Skulberg A. K. et al. Pharmacokinetics and-dynamics of intramuscular and intranasal naloxone: an explorative study in healthy volunteers// European journal of clinical pharmacology. 2018. С. 1-11.Vyas T. K. et al. Intranasal drug delivery for brain targeting // Current drug delivery. 2005. V. 2. № 2. С. 165-175.Vyas T. K. et al. Intranasal drug delivery for brain targeting // Current drug delivery. 2005. V. 2. № 2. С. 165-175.Appasaheb P. S. et al. A review on intranasal drug delivery system // Journal of Advanced Pharmacy Education & Research Oct-Dec. 2013. V. 3. № 4.Appasaheb P. S. et al. A review on intranasal drug delivery system // Journal of Advanced Pharmacy Education & Research Oct-Dec. 2013. V. 3. № 4.Vyas T. K. et al. Intranasal drug delivery for brain targeting // Current drug delivery. 2005. V. 2. № 2. С. 165-175.Vyas T. K. et al. Intranasal drug delivery for brain targeting // Current drug delivery. 2005. V. 2. № 2. С. 165-175.Lochhead J. J., Thorne R. G. Intranasal delivery of biologics to the central nervous system // Advanced drug delivery reviews. 2012. V. 64. № 7. С. 614-628.Lochhead J. J., Thorne R. G. Intranasal delivery of biologics to the central nervous system // Advanced drug delivery reviews. 2012. V. 64. № 7. С. 614-628.Привалова А. М., Гуляева Н. В., Букреева Т. В. Интраназальное введение перспективный способ доставки лекарственных веществ в мозг // Нейрохимия. 2012. Т. 29. № 2. С. 93-93.Privalova A. M., Gulyaeva N. V., Bukreeva T. V. Intranasal administration is a promising method of drug delivery to the brain // Neurochemistry. 2012. T. 29. № 2. P. 93-93.Kaur P. et al. In situ nasal gel drug delivery: A novel approach for brain targeting through the mucosal membrane // Artificial cells, nanomedicine, and biotechnology. 2016. V. 44. № 4. С. 1167-1176.Kaur P. et al. In situ nasal gel drug delivery: A novel approach for brain targeting through the mucosal membrane // Artificial cells, nanomedicine, and biotechnology. 2016. V. 44. № 4. С. 1167-1176.Sharma N. et al. Mucoadhesive thermoreversible nasal delivery system // Journal of Pharmacy Research. 2010. V. 3. С. 991-997.Sharma N. et al. Mucoadhesive thermoreversible nasal delivery system // Journal of Pharmacy Research. 2010. V. 3. С. 991-997.Karavasili C., Fatouros D. G. Smart materials: in situ gel-forming systems for nasal delivery //Drug discovery today. 2016. V. 21. № 1. С. 157-166.Karavasili C., Fatouros D. G. Smart materials: in situ gel-forming systems for nasal delivery //Drug discovery today. 2016. V. 21. № 1. С. 157-166.Agnese T. et al. Характеристики температуры, способствующей гелеобразованию различных полоксамеров // Фармацевтическая отрасль. 2013. № 5. С. 110-112.Agnese T. et al. Characteristics of the temperature conducive to the gelation of various poloxamers // Pharmaceutical industry. 2013. № 5. P. 110-112.European Pharmacopoeia 8.0 ed. 2014. 2820 c.European Pharmacopoeia 8.0 ed. 2014. 2820 c.Lindemann J. et al. Nasal mucosal temperature during respiration // Clinical Otolaryngology & Allied Sciences. 2002. V. 27. № 3. С. 135-139.Lindemann J. et al. Nasal mucosal temperature during respiration // Clinical Otolaryngology & Allied Sciences. 2002. V. 27. № 3. С. 135-139.Dayal P., Shaik M. S., Singh M. Evaluation of different parameters that affect droplet-size distribution from nasal sprays using the Malvern Spraytec® //Journal of pharmaceutical sciences. 2004. V. 93. № 7. P. 1725-1742.Dayal P., Shaik M. S., Singh M. Evaluation of different parameters that affect droplet-size distribution from nasal sprays using the Malvern Spraytec® //Journal of pharmaceutical sciences. 2004. V. 93. № 7. P. 1725-1742.

The authors declare that there are no conflicts of interest present.