Pharmaceutical Chemistry Journal Vol. 44, No.

10, 2011

DRUG SYNTHESIS METHODS

AND MANUFACTURING TECHNOLOGY

STUDYING AN ASSORTMENT OF SUPPOSITORY BASES (REVIEW)

T. G. Yarnykh,1 E. V. Tolochko,1 and V. N. Chushenko1

Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 44, No. 10, pp. 21 – 26, October, 2010.

Original article submitted March 24, 2010.

The existing assortment of suppository bases has been analyzed with respect to their physicochemical proper-
ties. The available data are systematized in the form of a table that provides the classification and summarizes
information on the composition, physicochemical properties, and manufacturers. The advantages and disad-
vantages of suppository bases and possibilities of their usage in ex tempore formulations depending on the
production technology and types (vaginal, rectal) are considered.
Key words: suppositories, suppository bases, drug technology.

Suppositories are today one of the most frequently used
drug forms. They are used to treat urological, gynecological,
proctological, and other types of diseases [1, 2].
Suppositories provide a therapeutic effect through the
complex action of drugs and the base, which is responsible
for the structural and mechanical or rheological properties.
The base is also one of the most important characteristics
that defines the stability of bound disperse systems.
The base makes up a large part of the suppository, exhib-
its certain physicochemical properties, and has a significant
influence on the drug bioavailability, therapeutic action,
evenness of the ingredient distribution, the accuracy of the
dose, etc.
Various types of suppository bases are offered on the in-
ternational pharmaceutical market under known trade brands
that differ in the length of the saturated acid hydrocarbon
chain and the ratio of glycerides. Therefore, the quality can
also differ. It is important to know the characteristic features
of each suppository base when conducting manufacturing
studies and preparing drugs.
Bases are classified as hydrophobic, hydrophilic, and
diphilic with respect to water.
Table 1 presents the results from an analysis of an assort-
ment of suppository bases.
1
National University of Pharmacy, Kharkiv, Ukraine.
e-mail: tl@ukrfa.kharkov.ua
Hydrophobic suppository bases
Hydrophobic suppository bases include fats and fat-like
substances that melt at body temperature and are of natural
or semi-synthetic origin.
Cocoa butter was for many years considered the best
base. Cocoa butter was first used as a base by the French
pharmacist Antuan Boom in 1766 [2]. Today cocoa butter is
used to prepare suppositories ex tempore and is included in
the pharmacopoeias of almost all countries.
This base if obtained from roasted and purified seeds of
the chocolate tree (Theobroma cacao, Streculeaceae) by hot
pressing. Cocoa butter is a solid natural plant fat [1, 2].
The advantageous qualities of cocoa butter are its misci-
bility with various drugs, rapid release of incorporated drugs,
sharply defined melting point, and high plasticity (especially
after adding a small amount of anhydrous lanolin).
The drawbacks of cocoa butter are its poor ability to
form emulsions (up to four drops per gram of butter), a ten-
dency toward polymorphism, content of viable microorgan-
isms, and short shelf-life.
According to the USA pharmacopoeia, cocoa butter is
used to prepare suppositories by rolling, pouring, and press-
ing [1, 3].
Laurel oil and coriander oil are used as cocoa butter sub-
stitutes.
Fatty oils of caraway and anise were isolated and studied
from plants of the family Umbelliferae. Their solid part con-
sisted of mainly triglycerides of petroselinic acid (about

551
0091-150X/11/4410-0551 © 2011 Springer Science+Business Media, Inc.
552 T. G. Yarnykh et al.

TABLE 1. Suppository Bases

Suppository base Composition Physicochemical properties Melting point, °C Manufacturer, country
Hydrophobic suppository bases
Cocoa butter (Oleum Triglycerides of higher fatty acids: Dense homogeneous mass, yel- 32.0 – 34.0 Ukraine, USA, etc.
Cacao seu Butyrum Ca- palmitic, oleic, lauric, stearic, arachic low with weak aromatic aroma
cao) and pleasant taste
Laurel butter (Oleum Derivatives obtained from kernels of Yellowish mass, solid consis- 34.0 – 35.0 Ukraine
Cinnamomi laurel fruit tency with pleasant aromatic
pedunculati) taste, melts in the mouth. Cocoa
butter substitute
Coriander butter Triglycerides of petroselinic acid, Cocoa butter substitute 30.0 – 31.0 Ukraine
(Oleum Coriandri) >50% of the dense part
Erticoat (Erticoat) Fractionated hydrogenation products Solid mass 35.0 – 37.0 Belgium
H-340 of palm and soy oils
Kuva-300 Fractionated hydrogenated paraffin Solid mass 38.0 ± 2.0 Loders Croclaan, Neth-
plant fat not based on laurel from plant erlands
oils (palm, soy, cotton, and peanut)
Kuva-500 Non-laurel fat, partially fractionated, Solid mass 35.0 ± 2.0 Loders Croclaan, Neth-
based on palm oil, raffinated erlands
Fat base 30% cocoa butter, 49-60% hydroge- Solid mass 38.0 ± 2.0 OAO Nizhfarm, Russia
nated sunflower oil (culinary fat) and
10-21% paraffin
GKhM-3T Mixture of hydrogenated peanut oil Solid mass with weak specific – Russia
with 3% T-2 emulsifier or aroma
propyleneglycol monostearate emulsi-
fier
GKhM-5T Mixture of hydrogenated cotton oil Solid mass with weak specific 36.0 – 37.0 Russia
with 4-5% T-2 emulsifier aroma
Supporinum-M Mixture with 95% hydrogenated cot- Light-yellow, homogeneous mass 34.0 – 36.0 Ukraine
ton oil and 5% T-2 emulsifier with weak specific aroma
Butyrol 50% hydrogenated fats, 20% paraffin, Solid mass from white to 37.0 ± 2.0 Ukraine
30% cocoa butter light-yellow with specific aroma
Salomas, various types Hydrogenation products of cotton or Solid mass from white to 32.0 – 34.0 Ukraine
sunflower oil with subsequent purifi- light-yellow with cream tint and
cation specific aroma
Lanolin base (Basic Lanolin 60 (80)%, hydrogenated fat 20 Solid homogeneous waxy mass, 35.5 – 37.5 Ukraine
Lanolum) (10)%, paraffin 20 (10)% white or with yellowish tint and
unique aroma
Solid confectionary fat Processed products of palm base and Solid base from white to 33.0 – 36.0 Ukraine
(Solides Adeps) types plastified salomas base light-yellow with cream tint and
A, B, C, E unique aroma
Sebuvinol Fraction of beef fat Solid mass. Has thickness of co- 36.0 – 37.0 Russia
(Sebuvinolum) coa butter
Massa Estarinum, types Mixture of mono-, di-, and triglycer- White mass, almost without 29.0 to 50.0 Dynamit Nobel Chemi-
A, B, C, D, E, T ides of saturated acids (lauric, myris- aroma and taste, melts at body cal, Great Britain
tic, palmitic, stearic) temperature forming colorless or
yellow liquid
Witepsol, types H, W, Mixture of mono-, di-, and triglycer- White crumbling solid, readily mp/solidification point, Dynamit Nobel Chemi-
S, E ides of plant acids C12—C18. Main melting mass without aroma and °C cal, Great Britain; Sasol
H-15 part, triglycerides of lauric acid taste 33.5 – 35.5 /32.0 – 34.5 Germany GmbH, Ger-
H-32 32.1 many
W-35 33.5 – 35.5 /27.0 – 30.0
E-75 37.0 – 39.0 /32.0 – 36.0
Novata, various brands Mixture of solid mono-, di-, and tri- White solid melting mass without Henkel, Germany
PK glycerides of saturated fatty acids aroma and taste 31.0 – 35.5
PKS C11—C17, alcohols C12—C20, and 38.0 – 40.0
non-ionizable polyethyleneglycol
PKS-37 36.0 – 37.5
emulsifiers
Lasupolum, brands G, Mixture of cetyl and stearyl alcohol White solid melting mass without 34.0 – 37.0 Germany
E, M phthalates aroma and taste
Studying an Assortment of Suppository Bases 553

TABLE 1. (Continued)

Suppository base Composition Physicochemical properties Melting point, °C Manufacturer, country

Estaram, types H, W, S, Semi-synthetic glycerides consisting White solid melting mass without 32.0 – 42.0 Croda Chemicals Eu-
E of a mixture of tri-, di-, and aroma and taste rope, Great Britain
monoglycerides of natural fatty oils
Supoweiss, types H, W, Semi-synthetic glycerides consisting White solid melting mass without 32.0 – 42.0 Croda Chemicals Eu-
S, E of a mixture of tri-, di-, and aroma and taste rope, Great Britain
monoglycerides of natural fatty oils
Fattibase Complex of fatty acid esters, 97% con- Matte colored base, paraffin-like, 32.0 – 35.0 Paddock Laboratories
sists of hydrogenated plant oil almost without aroma Inc., USA
Weecobee, brands M, Hydrogenation products of plant oil Solid mass without taste and 40.0 – 45.0 Stepan Company,
S, R, W aroma Northfield, Ill., USA
Hydrokote M Hydrogenation products of palm oil Solid whitish mass 36.0 – 39.0 Abitec Corporation, Co-
lumbus, OH, USA
Hydrophilic suppository bases
Gelatin—glycerin base Gelatin, 1 part; water, 2 parts; glyc- Homogeneous transparent mass – Ukraine, Russia, France,
(Massa gelatinosa) erin, 5 parts Hungary
Soap—glycerin base Crystalline sodium carbonate, 0.13; Suppositories prepared from this – Ukraine
(Mass sapo-glycerinata) glycerin, 3; stearic acid, 0.25 base are colorless, transparent,
Per single child/adult bar: crystalline hygroscopic, and as a rule, are Russia
sodium carbonate, 0.06/0.103; glyc- used without adding other drugs USA, Hungary,
erin, 1.44/2.460; stearic acid, Netherlands, Austria,
0.12/0.205 Poland
Polyethyleneoxides Polymers of ethylene oxide with over- PEO-300, 400, 600, colorless Solidification tempera- Ukraine, Russia, USA,
(PEO) all formula H(O–CH2CH2)nOH transparent viscous hygroscopic ture: France, Germany, etc.
(Polyaethylenoxyde, (n = 3-325) liquid with weak characteristic PEO-600 15.0 – 35.0;
Polyaethylenglycolum, aroma. PEO-1000, 1500, 3000, PEO-1000 35.0 – 40.0;
Carbowax, Scurol, 3350, 4000, 6000, 8000, 20000, PEO-1500 42.0 – 48.0;
Postonal) 35000, white or almost white PEO-3000 50.0 – 56.0;
hygroscopic paraffin-like solid PEO-3350 53.0 – 57.0;
mass PEO-4000 53.0 – 59.0;
PEO-6000 55.0 – 61.0;
PEO-8000 55.0 – 62.0;
PEO-20000/35000:
min 57.0
Diphilic suppository bases
Emulsogel Emulsogel No. 1: Manufactured solid emulsion has – Ukraine
Cocoa butter, 15.0; optimum characteristics of plas-
PEO-400, 15.0; ticity, elasticity, and viscosity
wax emulsion, 5.0,
PEO-1500, to 100.0;
Emulsogel No. 2:
Solid fat, 17.5;
Tween-80, 0.5;
PEO-400, 16.0;
PEO-1500 and PEO-4000 (1:1),
to 100.0;
Emulsogel No. 3:
Hydrogenated sunflower oil, 4.5;
Tween-800, 0.5;
PEO-400, 17.0;
PEO-4000, to 100.0

20%), the melting point of which was 29.0 – 31.5°C [1, 2, 4]. Hydrogenated plant oils are also widely used as supposi-
These oils have physicochemical and other properties that tory bases. This type of base includes Erticoat H-340 and
are similar to oil of coriander. Therefore, they can be used as Kuva. An advantage of the Kuva bases is that the non-laurel
suppository bases. fats from which they are produced are more stable than laurel
554
fats and combine well with cocoa butter. A fat base from
Gorkii CPP (OAO Nizhfarm) is used for industrial produc-
tion of suppositories in Russia and can also act as a cocoa
butter substitute [1, 2].
Combinations of hydrogenated plant oils with emulsifi-
ers belong to a separate group of hydrophobic suppository
bases.
The base GKhM-5T, which was developed by Yu. A.
Blagovidova and I. S. Azhgikhin, has properties that are
comparable with those of cocoa butter and has definite ad-
vantages because it contains T-2 emulsifier, which enhances
absorption of aqueous solutions and the assimilation of
drugs. The base is recommended for preparing suppositories
with various drugs by pouring. A. I. Tentsova and V. V.
Sergeev proposed the suppository base GKhM-3T. These
mixtures emulsify a large amount of water and aqueous drug
solutions, are compatible with compounds of various physi-
cochemical natures, are chemically inert to the human organ-
ism, and release drugs faster than from cocoa butter [2].
A team of scientists from Tashkent Pharmaceutical Insti-
tute proposed hydrophobic suppository bases based on
esterification products of locally produced plant oils (cotton,
olive, peach, sunflower) with various weight combinations
of animal fats and addition of emulsifiers No. 1, T-2, or
Tween-80. Preliminary structural-mechanical studies and nu-
merical indicators showed that the hydrophobic composition
with 5% T-2 emulsifier could be used as a suppository base [5].
The suppository base Supporin-M melts readily, is chem-
ically inert and non-toxic, quickly releases drugs, is easily
shaped, and does not cause rectal irritation [2].
Mixtures of hydrogenated fats with fat-like compounds,
emulsifiers, or hydrocarbon products are rather widely used
as cocoa butter substitutes. Compounds such as wax, paraf-
fin, and spermaceti are used to increase the melting point of
mixtures whereas lanolin, lecithin, cholesterol, etc. are used to
improve the miscibility of the resulting bases with water [1].
A mixture of hydrogenated fats with 4% paraffin called
Butyrol was first proposed in 1934 by A. G. Bosin. Today the
base butyrol consists of hydrogenated fats, paraffin, and co-
coa butter and has a thickness compared to cocoa butter of
66.5% [1, 2].
Hydrogenated fats are accepted by many pharmacopoe-
ias as suppository bases. Salomas and lanolin base are used
most frequently in Ukraine. The base confectionary solid fat
of several types is also produced in Ukraine. These differ in
the emulsifier content: type A, without emulsifier; type B,
5% No. 1 emulsifier; type C, up to 5% T-2 emulsifier; type E,
up to 5% wool wax alcohols. Confectionary solid fat type A
is recommended for production of suppositories containing
lipophilic drugs and suppositories for children; type B, for
suppositories containing water- and fat-insoluble powdered
drugs and liquid extracts [1, 2, 6].
Narrow fractions of glycerides with properties similar to
cocoa butter are separated from natural or hydrogenated fats
according to chemical or thermal indicators in order to pro-
T. G. Yarnykh et al.
duce thermal fractionation products from fats and hydroge-
nates.
The first base of this type was Sebuvinol, which had seri-
ous drawbacks such as rapid spoilage and formation of sup-
positories that were insufficiently plastic. This base was used
to prepare suppositories by pouring. I. S. Azhgikhin pro-
posed a mixture of acetone-soluble fractions of beef fat hy-
drogenates and palm-kernel oil. Removal of acetone pro-
duced solid products to which one of the emulsifiers T-2
(3%), propyleneglycolmonostearate (up to 5-10%),
saccharoglycerides (up to 0.5%), or sacccharose distearate
(up to 0.5%) was added to produce the base [1, 2].
Yet another group of hydrophobic suppository bases con-
sists of the products of directed esterification of high-molec-
ular-weight alcohols with semi-synthetic fatty acids. Bases
of fatty compositions containing fatty acid glycerides are
typically inert, have good structural and mechanical qualities
and the optimum ratio of melting and solidification points,
and are stable on storage [1].
The suppository base Estarinum is produced from
saponification products of cocoa butter and palm oil. Several
types of bases with different physicochemical properties are
manufactured. This group of bases has advantageous quali-
ties in that they do not spoil, do not form polymorphic modi-
fications, emulsify well aqueous solutions, and quickly solid-
ify [1, 7].
The base Witepsol is widely used in both industrial man-
ufacturing and pharmacy practice. Many types of this base
are available. This enables the optimum base with certain
physicochemical properties to be selected. The base has ad-
vantages since it is inert, does not form polymorphic modifi-
cations, emulsifies well aqueous solutions, and solidifies
quickly after melting. The time for complete deformation of
suppositories is up to 15 min [1, 2, 7]. A drawback of this
base is the possible fracture of manufactured suppositories.
Various brands of Novata and Lazupol bases are recom-
mended for preparation of suppositories with fat-soluble
drugs. These reduce the melting point of the suppositories [1].
The bases Estaram and Supoweiss are produced via
esterification of cocoa butter and/or palm oil free fatty acids
with glycerin (Estaram) or transesterification of hydroge-
nated plant oils. Several types of bases with different melting
points and physicochemical properties are manufactured.
Bases of type S are designed for preparation of vaginal sup-
positories. Bases of type E have high melting points and are
used to prepare suppositories with drugs that reduce the
melting point of the produced suppositories [1, 7].
The USA pharmacopoeia lists suppository bases
Fattibase and Weecobee. Fattibase is recommended for in-
dustrial application and for preparing suppositories by pour-
ing under pharmacy conditions. Weecobee is a new recently
formulated base and is manufactured under M, R, S, and W
brands that have different melting points [3].
Hydrophobic suppository bases PCCA Base in MBK
(based on processed fatty acids), A (based on Polyglycol
1450 MW, NF), and F (synthetic cocoa butter) brands;
Studying an Assortment of Suppository Bases
Hydrokote M, based on hydrogenated plant oil; COA Base,
based on processed fatty acids; and Supposibase, a mixture
of polyethyleneglycols and plant oil, are also used in the
USA [3, 7].
Hydrophilic suppository bases
This group of bases includes gelatin–glycerin, soap–
glycerin, and synthetic (polyethylene oxide) bases.
A characteristic feature of the bases is good solubility in
water. Drugs are assimilated from these bases independently
of their melting points because the assimilation is due only to
the rate of diffusion of the drugs from the base and the rate of
dissolution of the bases themselves. This group of bases is
used to prepare vaginal and rectal suppositories only by
pouring.
Gelatin–glycerin bases consist of gelatin, glycerin, and
water that are prescribed in different amounts in different
pharmacopoeias. The gelatin content can vary in the range
from 10 to 20%. The density of a gelatin—glycerin base de-
pends on the amount of gelatin. The less its amount is, the
softer the base is and the quicker it melts. The degree of des-
iccation, especially upon prolonged storage, depends on the
amount of glycerin. The greater the amount of it, the slower
the base becomes desiccated. Therefore, the amount of the
constituents varies as a function of the requirements placed
on the base [1, 2, 7].
The base melts at body temperature, mixes well with
compounds that are soluble in water and glycerin, and dis-
solves in vivo in mucous secretions.
A drawback of the base is the rapid multiplication in it of
microorganisms and degradation of the gelatin. Thus, sup-
positories prepared from this base have short shelf-lives.
This prevents them from being manufactured on an industrial
scale. Addition of decamethoxin to gelatin—glycerin bases
has been proposed for improving them. This increases the
shelf-life (up to four years) and makes possible industrial
production with various drugs. Decamethoxin acts as a pre-
servative [8].
Soap—glycerin bases are a solution of soap in glycerin.
The base is prepared by various methods depending on the
amount of starting materials. The Austrian and Polish phar-
macopoeias recommend preparing the soap from stearic acid
and sodium carbonate. Pharmacopoeias from other countries
(USA, Hungary, Netherlands) recommend preparing the base
by fusion of a prepared medicinal soap with glycerin [1-3, 7].
Suppositories prepared from soap—glycerin base are
used, as a rule, without added drugs. They exhibit a weak ef-
fect because they are local irritants that cause reflexive GI
peristalsis.
Polyethylene oxides (PEO) or polyethyleneglycols are
produced by polymerization of ethylene oxide in the pres-
ence of water and KOH. The consistency and properties of
PEO depend on the degree of polymerization [1, 4, 6, 9].
PEO of various extents of polymerization with molecular
masses from 400 to 6000 are manufactured in Russia and
Ukraine. PEO are prepared abroad with molecular masses
from 200 to 40,000 and more. These bases are known in the
555
USA under the name Carbowax; in France, Scurol; in Ger-
many, Postonal [3, 7].
Combining PEO of different consistencies can produce
bases with the required structural and mechanical properties.
Suppository bases are manufactured most often by fusing
PEO-400 and PEO-1500 in different ratios (1:9 and 2:8).
The advantages of PEO bases are the chemical and ther-
mal stability, stability to pH changes, lack of polymorphic
modifications, long shelf-life, resistance to effects of micro-
organisms, and insignificant bactericidal properties. Formu-
lations based on them do not require preservatives. They mix
readily with water and mucous secretions. The bases are
technologically advanced and simple to manufacture.
PEO bases have the following drawbacks. They are hy-
groscopic, dehydrate mucous membranes (antiphysiological
exosmosis, a drawback that is partially negated by immers-
ing the suppositories before use for several minutes in warm
water), and release drugs slower than other hydrophilic
bases. PEO bases are incompatible with several drugs (phe-
nols, resocin, tannin, iodides, bromides, salicylates, many
antibiotics and sulfanilamides, heavy-metal salts, silver,
etc.). Solutions of PEO have low viscosity and can flow out
of a cavity.
Diphilic suppository bases
Diphilic bases are compositions that contain hydrophilic
and hydrophobic parts. This enables both water- and fat-sol-
uble drugs and their solutions to be included in them.
Efforts on creating diphilic bases are directed to the pro-
duction of compositions that are stable in the aggregate and
are based on hydrophobic and hydrophilic components and
the formulation of bilayer suppositories.
Compositions of suppository bases with diphilic proper-
ties were developed in Russia. These include one based on
PEO-1500 and PEO-400 (9:1) as the hydrophilic phase and
confectionary solid fat, chicken fat, and olive, soy, or corn oil
as the hydrophobic phase with emulsifiers No. 1 or T-2 and
another based on PEO-400, PEO-1500, and GKhM-5T.
Tween-80 was used as the unifying component. Aerosil was
used to prepare compositions that were stable in the aggre-
gate.
The physicochemical properties of the aforementioned
bases satisfied requirements applied to suppository bases [1].
A base in which water (22 – 24%) and glycerin
(35 – 45%) were used as the hydrophilic phase; confection-
ary or baking fat, cocoa butter or Witepsol (22 – 26%), as the
hydrophobic phase, and gelatin, as a diphilic emulsifier was
reported. The resulting compositions were stable and homo-
geneous with melting point 35.5 ± 5.0°C. The fat—gelatin
complex accepts water- and fat-soluble drugs at any forma-
tion stage. This enables the drugs to be added as a prepared
complex or as separate components [1].
Formulations for diphilic bases with the arbitrary name
Emulsogel were developed at Zaporizhzhya State Medical
University. The technology for preparing the bases consists
of the following stages. The fat base (cocoa butter, solid fat,
etc.) is fused with surfactants (emulsion wax, MGD, etc.).
556
The mixture is treated with a melted mixture of PEO and
thoroughly stirred at 75.0 ± 5.0°C [10]. The base is used for
pressing and pouring methods.
Thus, the analysis of an assortment of suppository bases
showed that the repertoire of hydrophobic and hydrophilic
bases has grown considerably. This in turn facilitates a sig-
nificant expansion of their use in ex tempore formulations.
Research on the creation of suppository bases with various
given properties has recently been actively conducted.
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