Pre-clinical toxicological study of analogue of hypothalamic hormone tsifetrilin

Коняева, О. И.; Кульбачевская, Н. Ю.; Ермакова, Н. П.; Чалей, В. А.; Меркулова, И. Б.; Abramova, Tatiana; Бухман, В. М.; Shprakh, Z. S.

doi:10.17650/1726-9784-2018-17-2-63-70

Cited by 3 publications

(2 citation statements)

References 4 publications

(2 reference statements)

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“…Non-clinical studies of Cyphetrylin tablets pharmacokinetics showed the availability of Cyphetrylin for all studied organs and tissues, including brain and tumour [79]. And the results of non-clinical safety studies allowed to determine the initial (starting) safe dose for humans for phase I clinical trials [80].…”

Section: Fig 1: Structural Formula Of Cyphetrylinmentioning

confidence: 99%

Somatostatin Analogues for the Treatment of Neuroendocrine Tumours. Dosage Forms and Routes of Administration (Review)

Shprakh¹

2020

Int J App Pharm

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This review summarises information on drug products Somatostatin Analogues (SSAs), which are included in the algorithm of Neuroendocrine Tumors (NET) treatment. SSAs are the current standard for safe and effective management of NET symptoms and control of tumours growth and are administered in a range of dosage forms for parenteral administration, such as intramuscular, subcutaneous and implant. A search criterion was the therapy of NET with medicines from a group of SSAs. Literature survey has been done in a range of years 1990-2018 to make the review updated and comprehensive and to show the development of SSAs new pharmaceutical dosage forms to improve patient quality of life and side effects decrease. The sources were world-recognized journals. Keywords used as filters were NET, SSAs, octreotide, lanreotide, pasireotide, Somatostatin Receptors (SSTR), dosage form. The current review is created with an intended to focus on the advantage of SSAs modern dosage forms. Literature survey revealed that many studies were carried out to SSAs encapsulation into microspheres that changes the drug bioavailability and allows reducing the number of administration. Also, SSAs delivery systems in particular devices such as auto-injector have been created to control the continuous concentration of the drug and to provide safety guarantee. Besides, studies have been carried out to prepare SSAs formulations for oral administration to improve the quality of life of the NET patients. In this review, SSAs pharmaceutical dosage forms with improved pharmacokinetic and therapeutic characteristics and routes of administration are analyzed.

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Section: Fig 1: Structural Formula Of Cyphetrylinmentioning

confidence: 99%

Somatostatin Analogues for the Treatment of Neuroendocrine Tumours. Dosage Forms and Routes of Administration (Review)

Shprakh¹

2020

Int J App Pharm

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“…But cyphetrylin is insoluble in water, and it is metabolically stable in the gastric fluid because of reactive groups blocking. The specific studies of cyphetrylin in vivo showed its high antitumor efficiency on animal's experimental tumours and xenografts by oral administration [8,9].…”

Section: Introductionmentioning

confidence: 99%

Formulation and Evaluation of Somatostatin Analogue Tablets

Shprakh

Орлова²,

Оборотова³

et al. 2019

Int J App Pharm

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Objective: This study was undertaken with the aim of the formulation and evaluation of hypothalamic hormone somatostatin analogue tablets, which are intended for neuroendocrine tumours treatment. Methods: Tablets were prepared by using the wet granulation method and evaluated for weight variation, resistance to crushing, friability, disintegration time, content and content uniformity. Stability tests have been performed. Results: Characteristics of somatostatin analogue cyphetrylin powder have been investigated, and the wet granulation method has been chosen to prepare tablets. Technical pharmaceutical properties of formulations of different compositions and obtained tablets were estimated and the best formulation CF11 has been established with appropriate characteristics: disintegration time less than 15 min, resistance to crushing more than 30 kg·m·s−2, weight variation ˂7.5 %, active substance content closed to the nominal quantity and consistent cyphetrylin distribution in the batch. Performed examinations showed cyphetrylin tablets stability in the long-term study. Conclusion: Because of somatostatin analogue cyphetrylin powder properties tablets were prepared by the wet granulation method with starch, lactose, povidone, talc, microcrystalline cellulose, calcium stearate and magnesium stearate as excipients. The best formulation including povidone has characteristics corresponding to requirements of European Pharmacopoeia (PhEur) and State Pharmacopoeia of the Russian Federation (PhRu). Examination of cyphetrylin tablets showed its quality and stability within the time of observation–12 mo.

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Determination of Optimal Technological Conditions for the Process of Production a Liposomal Dosage Form of Cyphetrylin

Дмитриева¹,

Орлова²,

Ланцова³

et al. 2022

Razrabotka i registraciâ lekarstvennyh sredstv

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Introduction. The Laboratory for the development of dosage forms of the N. N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of Russian Federation has developed a composition of an injectable liposomal dosage form based on soybean phosphatidylcholine, a hydrophobic analog of the hypothalamic hormone somatostatin − cyphetrylin, intended for the treatment of neuroendocrine tumors.Aim. Determination of optimal technological conditions for the process of obtaining a liposomal dosage form of cyphetrylin.Materials and methods. The study used the substance cyphetrylin synthesized in the of Chemical Synthesis Laboratory of the N. N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of Russian Federation; soybean phosphatidylcholine S PC and polyethylene glycol-2000-distearoylphosphatidylethanolamine, produced by Lipoid GmbH (Germany); cholesterol ≥99 % (Sigma-Aldrich, Japan). For the preparation of phospholipid vesicles loaded with cyphetrylin and "empty", the methods of lipid film hydration with subsequent extrusion or homogenization of the dispersion of multi-layer liposomes were used. The obtained liposomal samples were evaluated by quality indicators − the effectiveness of the inclusion of cyphetrylin in vesicles, their average size and surface charge (zeta potential), the viscosity of the dispersion. To evaluate these characteristics, the methods of spectrophotometry, laser scattering spectroscopy, determination of the electrophoretic mobility of particles and viscometry were used.Results and discussion. It was found that the most suitable organic solvent for obtaining a solution of cyphetrylin and lipid components of the dosage form is chloroform. The duration of the drying period of the lipid film under vacuum to remove the residual solvent is determined by the ratio of the volume of the distillation flask used and the mass of its loading its loading. At the same time, hydration off the lipid film with water for injection should be carried out under conditions of low-pressure and room temperature. To obtain a dispersion of single-layer cyphetrylin liposomes of the required size, an extrusion method using nylon and polycarbonate membranes with a filter pore diameter of 0.22 and 0.2 um, respectively, was chosen.Conclusion. The optimal technological conditions for the process of obtaining a liposomal dosage form in the form of a dispersion of a hydrophobic analog of the hypothalamic hormone somatostatin − cyphetrylin are determined.

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Pre-clinical toxicological study of analogue of hypothalamic hormone tsifetrilin

Cited by 3 publications

References 4 publications

Somatostatin Analogues for the Treatment of Neuroendocrine Tumours. Dosage Forms and Routes of Administration (Review)

Somatostatin Analogues for the Treatment of Neuroendocrine Tumours. Dosage Forms and Routes of Administration (Review)

Formulation and Evaluation of Somatostatin Analogue Tablets

Determination of Optimal Technological Conditions for the Process of Production a Liposomal Dosage Form of Cyphetrylin

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