Изучение консистентных свойств интраназальной лекарственной формы винпоцетина

Тип работы:
Реферат
Предмет:
Медицина


Узнать стоимость

Детальная информация о работе

Выдержка из работы

UDC 615. 22. 032. 21. 011. 4
N. A. Nagornaya, V. V. Gladyshev, B. S. Burlaka
Study of vinpocetine intranasal dosage form consistence properties
Zaporozhye State Medical University Key words: Vinpocetine, Intranasal Drug Administration, Rheology, «Mechanical Stability».
Aim. Study of structural-mechanical nasal semisolid dosage forms on emulsion bases providing with optimal release active substance was done.
Methods and results. Established vinpocetine nasal creams rheologic properties showed them as thixotropic systems. Restoration after stress removal is cuased by their structure coagulation bonds. Their consistent properties are completely situated within rheologic optimum of consistence limits.
Conclusion. Analysis of rheograms of flow allowed to reveal compositions of vinpocetine nasal emulsion ointments with optimal consistent properties and selected for the next preclinical investigations.
Вивчення консистентних властивостей штраназальноТ лжарськоТ форми вшпоцетину
Н. О. Нагорна, В. В. Гладишев, Б. С. Бурлака
Здшснили дослщження структурно-мехашчних штраназальних м'-яких лжарських форм вшпоцетину на емульсшних носшх, що за-безпечують оптимальне вившьнення з них дшчо! речовини. Виявили, що реолопчш властивоста дослвджених штраназальних кремш вшпоцетину характеризуюсь! х як тиксотропш системи, у структурi яких домiнують коагуляцiйнi зв'-язки, яю забезпечують! х повне вiдновлення тсля зняття напруження, i чи! консистентт властивостi знаходяться в межах оптимуму реологи мазей. Аналiз реограм течи композицш дозволив встановити склади назальних емульсiйних мазей iз вiнпоцетином, що мають оптимальш консистентнi властивостi й обраш для подальшого доклiнiчного вивчення.
Ключовi слова: втпоцетин, ттраназальт препарати, реологiя, «мехатчна стабтьтсть».
Запор1зький медичний журнал. — 2014. — № 5 (86). — С. 97−100
Изучение консистентных свойств интраназальной лекарственной формы винпоцетина
Н. А. Нагорная, В. В. Гладышев, Б. С. Бурлака
Проведены исследования структурно-механических интраназальных мягких лекарственных форм винпоцетина на эмульсионных носителях, обеспечивающих оптимальную высвобождаемость из них действующего вещества. Установлено, что реологические свойства изученных интраназальных кремов винпоцетина характеризуют их как тиксотропные системы, в структуре которых доминируют коагуляционные связи, обеспечивающие их полное восстановление после снятия напряжений, и чьи консистентные свойства полностью находятся в пределах реологического оптимума мазей. Анализ реограмм течения композиций позволил установить составы назальных эмульсионных мазей с винпоцетином, обладающих оптимальными консистентными свойствами и отобранных для дальнейшего доклинического изучения.
Ключевые слова: винпоцетин, интраназальные препараты, реология, «механическая стабильность».
Запорожский медицинский журнал. — 2014. — № 5 (86). — С. 97−100
Structural-mechanical characteristics of compositions have a marked influence on medicinal substances processes of releasing and absorption from the ointments and also on their consumer features: spreading, adhesion, capacity of squeezing out from the tubes [1,2,3].
Patient associates convenience and easiness of ointment applying on tissue or mucous membrane with efforts that are used to spread on the skin certain amount of ointment. That is similar to the process going on during movement of viscous and plastic material in the rotational viscosimeter, and patient'-s effort is a shear stress which characterizes resistibility of the materials to shear deformations by certain rate and can be measured instrumentally.
So the assessment of rheologic characteristics is an important and integral part of investigations in making of semisolid dosage forms for dermatological practice [5, 6].
As a result of complex physico-chemical, pharmacotech-nological and biopharmaceutical investigations a formulation of nasal semisolid dosage form with vinpocetine — vasoactive biologically active substance which improves cerebral blood
© N. A. Nagornaya, V. V. Gladyshev, B. S. Burlaka, 2014
circulation for angioneurologic practice was proposed by the department of Medicinal Preparations Technology of Zaporozhye State Medical University [7 — 9].
The aim of this work is study of consistent properties of developed ointment composition for treatment of cerebralvas-cular pathology.
Materials and methods
For the rheological investigations 0,5% vinpocetine ointments on emulsion bases providing with optimal releasing from the dosage form were used [10]. Formulations of vinpocetine nasal compositions are presented at table 1.
Study of structural-mechanical characteristics of compositions was carried out by the rotary viscosimeter «Reotest-2» with cylindrical arrangement. For the establishment of the consistent properties of system the sample of ointment composition was put in measurement device and then in thermostat during a half of an hour by the temperature 20 °C. Then cylinder was rotated in measurement device by the twelve increasing in consecutive order shear rates, and readings of the indicated device were registered on each level. Destruction of studying system was carried out by the rotation of cylinder in measurement device in
Table 1 maximum rate during 10 minutes and after stopping of rotation on 10 minutes readings of the indicated device were registered on each of twelve decreasing rates. On the base of received results the value of maximum shear stress and efficient viscosity were calculated and rheograms of flow were drown [11].
By the degree of structure permission of investigated systems in process of irreversible deformations it was judged using the value of «mechanical stability» which was calculated as ratio of strength limit before destruction to strength limit after destruction [12]. Results and discussion
Results of establishment dependence of efficient viscosity from shear rate for intranasal ointments with vinpocetine are presented at the tab. 2−4 and they indicate presence of structure in gel systems because under the influence of increasing deformation forces their maximum shear stress is increased and efficient viscosity is decreased.
Table 2
Values of shear stress and efficient viscosity of intranasal ointment emulsion formulation with vinpocetine 0,5% № 5
Shear rate, Dsec-№ Shear stress, (Pas) Viscosity (Pas^sec) Shear rate, Dsec-№ Shear stress (Pas) Viscosity (Pas^sec)
3 86,67 28,89 1312 392,62 0,30
5,4 90,69 16,79 729 357,03 0,49
9 119,97 13,33 437,4 301,92 0,69
16,2 154,41 9,53 243 237,64 0,98
27 189,99 7,04 145,8 189,42 1,30
48,6 211,81 4,36 81 135,46 1,67
81 235,91 2,91 48,6 109,06 2,24
145,8 280,69 1,93 27 90,69 3,36
243 316,27 1,30 16,2 83,23 5,14
437,4 383,43 0,88 9 76,92 8,55
729 436,81 0,60 5,4 69,45 12,86
1312 460,35 0,35 3 66,01 22,00
Table 3
Values of shear stress and efficient viscosity of intranasal ointment emulsion formulation with vinpocetine 0,5% № 6
Shear rate, Dsec-№ Shear stress, (Pas) Viscosity (Pas^sec) Shear rate, Dsec-№ Shear stress, (Pas) Viscosity (Pas^sec)
3 82,08 27,36 1312 409,26 0,31
5,4 86,10 15,94 729 354,73 0,49
9 115,37 12,82 437,4 299,63 0,69
16,2 149,81 9,25 243 235,34 0,97
27 185,40 6,87 145,8 187,12 1,28
48,6 204,92 4,22 81 133,17 1,64
81 231,32 2,86 48,6 106,76 2,20
145,8 276,09 1,89 27 88,40 3,27
243 311,68 1,28 16,2 80,93 5,00
437,4 368,51 0,84 9 74,62 8,29
729 413,85 0,57 5,4 67,16 12,44
1312 455,76 0,35 3 63,71 21,24
Table 4
Values of shear stress and efficient viscosity of intranasal ointment emulsion formulation with vinpocetine 0,5% № 9
Shear rate, Dsec-№ Shear stress, (Pas) Viscosity (Pas^sec) Shear rate, Dsec-№ Shear stress, (Pas) Viscosity (Pas^sec)
3 110,78 36,93 1312 310,53 0,24
5,4 128,00 23,70 729 251,41 0,34
9 134,89 14,99 437,4 220,42 0,50
16,2 139,48 8,61 243 188,85 0,78
27 141,78 5,25 145,8 158,42 1,09
48,6 149,81 3,08 81 135,46 1,67
81 161,29 1,99 48,6 121,69 2,50
145,8 184,83 1,27 27 114,23 4,23
243 211,23 0,87 16,2 112,50 6,94
437,4 235,34 0,54 9 103,89 11,54
729 270,35 0,37 5,4 97,58 18,07
1312 321,44 0,25 3 90,69 30,23
© N. A. Nagornaya, V. V. Gladyshev, B. S. Burlaka, 2014
Composition of intranasal ointment emulsion formulations with vinpocetine 0,5%
Components Bases (№№), %%
5 6 9
Vinpocetine 0,5 0,5 0,5
Glycerine 15 5
Twin 80 2 2
Sunflower seed oil 15 15
Distilled monoglycerides 4 8
Emulsifier № 1 7,5
Vaseline oil 20
Emulsion wax 6
Monostearate glycerine 5
Oleate-PEG-400 5
stearate-PEG-400 5
Ester II 3
Distilled water to 100 100 100
98
ISSN 2306−4145 ЗАПОРОЖСКИЙ МЕДИЦИНСКИЙ ЖУРНАЛ № 5 (86) 2014
Rheograms of flow of intranasal ointment emulsion formulations with vinpocetine are presented on fig. 1−3.
1200
1000
i 600
Ш

Q 400 200
0,00 100,00 200,00 300,00 400,00 600,00
-Formulation № 5 T'- Pas
— - Optimum of consistence
Fig. 1. Rheogram of intranasal ointment emulsion formulation with
vinpocetine 0,5% № 5.
1200
1000
800
600
400
200
0,00 100,00 200,00 -Formulation № 6
300,00
400,00 500,00 t, Pas
1200
400
200
o. oo
100,00 200,00 300,00 400,00 500,00
t, Pas
Optimum of consistence
Fig. 2. Rheogram of intranasal ointment emulsion formulation with vinpocetine 0,5% № 6.
Drown rheograms indicate that flow begins not instantly but after some applied stress necessary for the burst of structure elements. Tangent stress slowly increases with increasing of deformation rate to certain value. In period of again stress decreasing viscosity of investigating systems is restored permanently. That fact confirms the presence of plastic and viscous and thixotropic properties in intranasal ointment emulsion formulations with vinpocetine.
-Formulation № 9
Optimum of consistence
Fig. 3. Rheogram of intranasal ointment emulsion formulation with vinpocetine 0,5% № 9.
It is significant that in period of again stress decreasing restoration of structure is permanently late. On the rheograms descending and ascending curves of all formulations form «hysteresis loop» with area for vinpocetine nasal ointments on the bases № 5 and 6 much more larger than the same for base № 9. That indicates bigger thixotropy and better consistent properties of their optimum of ointment consistence limits. Rheograms of all investigated vinpocetine intranasal dosage forms are completely situated within rheologic optimum of consistence limits [13].
Calculated «mechanical stability» vinpocetine nasal emulsion ointments on the bases № 5 and 6 is 1,33.
It indicates that just coagulation bonds which provide with full deformation reversibility after removal of tension and keeping of rheological properties during long storing are presented in their structure [14].
Conclusion
1. Rheologic properties of the investigated vinpocetine nasal ointments on emulsion base characterize them as thixotropic systems and in their structure coagulation bonds prevail and ensure restoration after stress removal.
2. It was revealed that consistent properties of all investigated nasal systems are completely situated within rheologic optimum of consistence limits.
3. On the grounds of comparative estimation of rheological features for vinpocetine nasal semisolid dosage form and taking into account results of biopharmaceutical characteristics emulsion ointment № 5 and № 6 were offered to the next investigations.
References
1. Rybachuk, V. D., Trutaiev, I. V., & amp- Yehorov, I. A. (2005) Vyvchen-nia reolohichnykh vlastyvostei novoi kombinovanoi mazi dlia likuvannia alerhichnyhk dermatytiv [Studying of rheological behaviour of the new combined ointment for treatment allergic dermatit]. Visnyk farmatsii, 3(43), 32−34. [in Ukrainian].
2. Hrytsenko, V. I., Chuieshov, V. I., & amp- Ruban, O. A. (2004) Rozrobka matematychnoi modeli reolohichnyhk parametriv polietylenoksyd-
noi osnovy [Working out of a mathematical model of rheological parametres polyetilenoxed bases]. Farmatsevtychnyi zhurnal, 5, 81−84. [in Ukrainian].
3. Kryklyva, I. O., Ruban, O. A., & amp- Chuieshov, V. I. (2002) Vyvchen-nia strukturno-mehkanichnyhk vlastyvostei novoi kombinovanoi mazi z kseroformom [Studying of structurally-mechanical characteristics new combined ointment with xerofopM]. Visnykfarmatsii, 2(30), 14−16. [in Ukrainian].
© N. A. Nagornaya, V. V. Gladyshev, B. S. Burlaka, 2014
4. Percev, I. M., Kotenko, A. M., Chueshov, V. I., & amp- Khaleeva, E. L. (2003). Farmacevticheskie i biologicheskie aspekty mazej [Pharmaceutical and biological aspects of ointments]. Kharkov: Zolotye stranicy. [in Ukrainian].
5. Dyudyun, A. D., Gladyshev, V. V., & amp- Nagornyj, V. V. (2002) Optimizaciya metodologii biofarmacevticheskikh issledovanij pri razrabotke tekhnologii myagkikh lekarstvennykh form dlya terapii dermatomikozov [Optimisation of methodology of biopharmaceutical researches by working out of technology of soft medicinal forms for therapy dermatomycoses]. Dermatovenerolohiia, kosmetolohiia, seksopatolohiia, 1−2(5), 13−16. [in Ukrainian].
6. Gladyshev, V. V., Nagornyj, V. V., Brazhko, A. A, & amp- Golovkin, V. V. (2002) Optimizaciya metodologii biofarmacevticheskikh issledovanij pri razrabotke tekhnologii parafarmacevticheskikh sistem [Optimisation of methodology of biopharmaceutical researches by working out of technology of parapharmaceutical systems]. Visnyk Zaporizkoho derzhavnoho universytetu, 1, 158−161. [in Ukrainian].
7. Chernij, V. I., Kolesnikov, A. N., Gorodnik, H. A., & amp- Savchenko, A. A. (2007). Ishemiya golovnogo mozga v medicine kriticheskikh sostoyanij. Nejroprotekciya (patofiziologiya, terminologiya, kharakteristika preparatov) [Brain ischemia in medicine of critical states. Neuroprotection (physiopathology, terminology, the characteristic of drugs)]. Kiev: Zdorov'-a. [in Ukrainian].
8. Belenichev, I. F., Chernii, V. I., Kolesnik, Yu. M., & amp- Pavlov, S. V. (2009). Racional '-naya nejroprotekciya [Rational neuroprotection]. Doneck: Isdatel Zaslavskij A. Yu. [in Ukrainian].
9. Rumyantseva, S. A., Afanas'-ev, V. V., Kuz'-mina, Yu. V., & amp- Silina, E. V. (2010). Racional'-naya farmakokorrekciya porazhenij mozga pri ostroj i khronicheskoj ishemii [Rational pharmacological
correction of lesions of a brain at a sharp and chronic ischemia]. Consilium Medicum, 12(9). 23−31. [in Russian].
10. Nahorna, N. O., Hladyshev, V. V., Burlaka, B. S., Kechin, I. L. (2014). Vyvchennia vplyvu osnov-nosiiv na intensyvnist vyvilnen-nia vinpotsetynu z nazalnych miakyhk likarskykh form [Studying of influence of bases-carriers on intensity of liberation vinpocetin from nasal soft medicinal forms]. Farmatsevtychnyi zhurnal, 2, 64−67. [in Ukrainian].
11. Hladyshev, V. V. (1997). Teoreticheskoe i eksperimental'-noe obosnovanie sozdaniya myagkikh lekarstvennykh form anti-mikoticheskogo dejstviya (Dis… dokt. med. nauk). [Theoretical and experimental substantiation of building of soft medicinal forms antimycotic actions: the dissertation of the doctor of pharmaceutical sciences. Dr. med. sci. diss.]. Zaporozhye. [in Ukrainian].
12. Tencova, A. I., Greckij, V. M. (1980). Sovremennye aspekty issledovaniya i proizvodstva mazej [Modern aspects of research and production of ointments]. Moscow: Medicina. [in Russian].
13. Arkusha, A. A. (1982). Issledovaniestrukturno-mekhanicheskikh svojstv mazej s cel '-yu opredeleniya optimuma konsistencii (Av-toref. dis. kand. med. nauk). [Research structurally-mechanical characteristics ointments for the purpose of definition of an optimum of a consistence: the dissertation autoabstract on competition of a scientific degree of the candidate of pharmaceutical sciences]. (Extended abstract of candidate'-s thesis). Kharkov. [in Ukrainian].
14. Golovkin, V. V., Golovkin, V. A., & amp- Gladyshev, V. V. (2001). Strukturno-mekhanicheskie svojstva osnov-nositelej, ikh regu-lirovanie i znachenie dlya vaginal '-nykhpreparatov [Structurally-mechanical properties of bases-carriers, their regulation and value for vaginalis drugs]. Zaporozhskijmedicinskijzhurnal, 1−2. 64−67. [in Ukrainian].
Information about authors:
Nagornaya N.A., post graduate student of Department of Medicinal Preparations Technology, Zaporizhzhya State Medical University. Gladyshev V.V., head of Department of Medicinal Preparations Technology, Zaporizhzhya State Medical University, Professor, Doctor of pharmaceutical sciences, E-mail: gladishevvv@gmail. com. Burlaka B.S., Associate professor of Department of Medicinal Preparations Technology, Zaporizhzhya State Medical University, PhD.
Поступила в редакцию 15. 07. 2014 г.
ISSN 2306−4145 ЗАПОРОЖСКИЙ МЕДИЦИНСКИЙ ЖУРНАЛ № 5 (86) 2014

ПоказатьСвернуть
Заполнить форму текущей работой