Creation of Cocoa butter bases for preparation of suppositories in pharmacy condition by the casting method
V. M. Chushenko, T. G. Yarnykh, G. B. Yuryeva, I. V. Herasymova
Technology of Drugs Department, National University of Pharmacy, 61002,
Pushkinskaya St. 53, Kharkiv, Ukraine.
*Corresponding Author E-mail: iryna_herasymova@ukr.net
ABSTRACT:
Purpose. The aim of the study is to create of cocoa butter bases for the preparation of suppositories in pharmacy condition with a various active pharmaceutical ingredients by casting method, which is hygienic, convenient, fast and efficient. Methods. In the process, we used physical-chemical and pharmaco-technological methods of researches to study the basic properties of suppositories. Results. The conditions for the creation of cocoa butter bases with various emulsifiers for the manufacture of suppositories in pharmacy condition by the casting method have been studied. The ratio between the cocoa butter and emulsifiers at which it is possible to prepare suppository bases has been established. Conclusions. Based on the conducted research a cocoa butter bases with emulsifiers have been developed. Suppositories prepared by casting method were compatible with the requirements to suppository bases of the State Pharmacopoeia of Ukraine 2.0.
KEYWORDS: Suppositories, Technology, Suppository base, Cocoa butter, Pharmacy.
INTRODUCTION:
Suppository bases of various nature are represented on the international pharmaceutical market. Such bases as: Macrogols (polyethylene oxides - PEO), Witepsol, Solid fat, etc. are most often use in pharmaceutical industry[5].
Macrogols are mixture of polymers - hydrophilic synthetic bases. The type of macrogol is indicated by a number which marks the average relative molecular weight. They obtained by combination of polyethylene oxides with a different molecular weights from 300 to 35000. These bases have the following disadvantages: high osmosis caused to dehydration of the mucous membrane at the place of introduction, reducing the rate of absorption of medicinal substances, incompatibility with a some drugs[5,6].
Witepsol is the hydrophobic suppository base of synthetic origin. It marks by letters H, W, S, E. This base is the most frequently used in modern technology. The base is indifferent, compatible with many active pharmaceutical ingredients (API), well emulsifies aqueous solutions. The disadvantage of this base is a brittleness of suppositories.
Solid fat of various types A, B, C, E is a hydrophobic base, which is used for the manufacture of suppositories with hydrophobic substances. The following disadvantages of this base: immiscibility with hydrophilic APIs, decreasing of the melting temperature of prepared suppositories with aqueous or oily solutions of medicinal substances.
The suppository bases mentioned above are of semi-synthetic or synthetic origin cause discomfort while application or allergic reactions in patients, whereas suppository bases of natural origin do not have such consequences[7,8].
Cocoa butter belongs to the natural hydrophobic bases and for many years is considered the best base of natural origin. The base is obtained by hot pressing from roasted and peeled chocolate tree seeds (Theobroma Cacao, Streculeaceae)[9].
Cocoa butter has a some of significant advantages: it mixes well with various medicinal substances, quickly releases the introduced medicinal substances, has a distinct melting point and high plasticity, and also has a pronounced reparative and lubricating effect. It can used as an independent suppository base, but its preparation requires strict adherence to the temperature regime in order to prevent the phenomenon of polymorphism. The melting point of the oil is 30-34°C, it mixes well with API. Adding a small amount of anhydrous lanolin cause to forming a plastic mass. When heated above 35°C, it is difficult to harden, therefore it is used only for the rolling and pressing method of suppositories preparation.
Suppositories and pessaries can prepared by three methods: rolling (manual), casting into forms and pressing. To obtain suppositories and pessaries by the rolling method, cocoa butter or its substitutes are used; by pressing method – cocoa butter, butyrol, PEO (some of them are soften while pressing); by casting method – water-soluble and all fatty bases (except cocoa butter, which while heating forms a low-melting modification).
The method of rolling does not require a special equipment, but it is not economically efficient, since a lot of hand work is spent. The obtained products have a worse appearance than in the manufacture condition using devices of mechanization.
Purpose:
The aim of the study is to create of cocoa butter bases for the preparation of suppositories in pharmacy condition with a various API by casting method, which is hygienic, convenient, fast and efficient.
MATHERIALS AND METHODS:
Cocoa butter was used as a base; as excipients the following substances are used: lecithin (USP 32-NF 27, P. 1131) or lecithin -dietary supplement (firm Art Life, Technical specifications 9197-042-12424-308-14), МGD (distilled monoglycerides– USP 40-NF 35), CSA (cetostearyl alcohol - EP 2005, BP, USP NF САS № 67762-27-0)і № 8005-44-5) and purified water according to the SPhU 2.0, P. 129.
Suppository bases were prepared on the basis of cocoa butter with emulsifiers (lecithin, МGD, CSA) in different ratio.
In the process of physical-chemical and pharmaco-technological methods of researches the main properties of suppositories were established in accordance with the requirements of SPhU 2.0. The melting point of the samples was determined by the open capillary method according to SPhU 2.0, 2.2.15. The disintegration of the suppository bases was performed according to SPhU 2.0, 2.9.2 using the PTS 3E device for determining the decay of the suppositories, resistance to breakage-in accordance with SPhU 2.0, 2.9.24.
Human and animal rights:
This article does not contain any studies with human and animal subjects performed by any of the authors.
RESULTS AND DISCUSSION:
In the pharmaceutical technology, the following emulsifiers are used to obtain a stable water/oil emulsions (with HLB 3-6): T-2, CSA, МGD, lecithin, etc. That is why the above emulsifiers were used to improve the composition of cocoa butter base for suppositories preparation by the casting method [10].
For the preparation of various compositions 100.0g of bases for suppositories each took 1.0g, 5.0g and 10.0g of CSA and МGD, and 99.0g, 95.0g and 90.0g of cocoa butter, respectively. Each of the suppository base composition was obtained as follows: in the porcelain cup CSA and МGD were melted on the water bath at the two temperature regimes 50.0±2.0°C and 65.0±2.0°C respectively. The porcelain cup was removed from the water bath, some amount of cocoa butter was added and mixed to form a homogeneous mass. With constant stirring, another part of cocoa butter was added, and then, the remaining amount of cocoa butter was added to the mixture and thoroughly mixed until the final melting of the cocoa butter and the formation of a homogeneous mass (if necessary, was heated on the water bath). The obtained base was poured into forms.
1.0g, 5.0g and 10.0g of lecithin were placed in a heated mortar, 3ml, 15ml and 25ml of purified water (according to lecithin concentration of 1%, 5% and 10%), heated to a temperature (30.0±1.0)°C were added, stirred, triturated to obtain a homogeneous lecithin emulsion for 20 minutes. Cocoa butter was placed in the cups (96.0g, 80.0g and 65.0g, respectively), heated to the kindling and added gradually to the mortars, mixing with lecithin emulsion until a homogeneous mass was formed, then transferred to the cups (if necessary, heated in a water bath ). The resulting base was poured into forms.
Suppository bases prepared according to variant I (cocoa butter with 1% CSA, 1% МGD and 1% lecithin) were soft in appearance and easily crushed. Therefore, further studies with these bases were not performed.
In terms of their appearance, the base samples obtained according to the II and III variants of the technology met the requirements of the State Pharmacopoeia of Ukraine 2.0. Experimental samples of bases formed in the form of suppositories: cocoa butter and CSA, cocoa butter and МGD, cocoa butter and lecithin were prepared in the ratio indicated above by the casting method. The composition of suppository bases are given in Table 1 and 2.
Table 1. The composition of suppository bases
|
Ingredients |
Content of substances in the bases, g |
|||||
|
І |
ІІ |
ІІІ |
||||
|
Cocoa butter |
99.0 |
99.0 |
95.0 |
95.0 |
90.0 |
90.0 |
|
CSA |
1.0 |
-- |
5.0 |
-- |
10.0 |
-- |
|
МGD |
-- |
1.0 |
-- |
5.0 |
-- |
10.0 |
Table 2. The composition of suppository bases
|
Ingredients |
Content of substances in the bases, g |
||
|
І |
ІІ |
ІІІ |
|
|
Cocoa butter |
96.0 |
80.0 |
65.0 |
|
Lecithin |
1.0 |
5.0 |
10.0 |
|
Water |
3.0 |
15.0 |
25.0 |
The quality indicators of suppository bases obtained in the two variants (II and III) mentioned above (cocoa butter with 5% and 10% CSA, cocoa butter with 5% and 10% МGD, and cocoa butter with 5% and 10% lecithin) are given in Table 3.
Samples of the bases obtained in the ratio 95:5 and 90:10, were solid and uniform. The results of the above bases in terms of melting point, disintegration time and resistance to fracture are presented in table. 3
Table3. Quality indicators of the suppository bases samples
|
Base composition |
Quality indicators of bases |
Requirements of SPhU 2.0 |
Conclusion |
|
The melting point of suppositories, °С |
|||
|
ІІ +III variant (CSA) 5 % 10 % |
36.6 36.8 |
Not more 37 ˚С |
Meets the requirements of SPhU2.0 |
|
ІІ+III variant (МGD) 5 % 10 % |
36.6 36.8 |
Meets the requirements of SPhU 2.0 |
|
|
II+III variant (lecithin) 5 % 10 % |
36.7 36.4 |
Not more 37 ˚С |
Meets the requirements of SPhU 2.0 |
|
Disintegration time, min |
|||
|
ІІ+III variant (CSA) 5 % 10 % |
14min 15 sec 15min 08 sec |
Not more 30 min |
Meets the requirements of SPhU2.0 |
|
II+ІІІ variant (МGD) 5 % 10 % |
13 min 25 sec 14 min 21sec |
Meets the requirements of SPhU2.0 |
|
|
II+III variant (lecithin) 5 % 10 % |
17 min 28 sec 12min 13 sec |
Not more 30 min |
Meets the requirements of SPhU2.0 |
In the study of resistance to destruction of suppository base samples with cocoa butter and emulsifiers of the CSA and МGD 5% and 10%, it was proved that the samples with stand loads from 1.3 kg to 1.6 kg (Table 4).
Table4. The results of resistance to the base destruction
|
Composition of base |
Resistance to the base destruction, kg |
|
ІІ+III variant (CSA) 5 % 10 % |
1.3 -1.4 1.4-1.5 |
|
II+ІІІ variant (МGD) 5 % 10 % |
1.4 -1.5 1.5 -1.6 |
|
II+III variant (lecithin) 5 % 10 % |
1.9 – 2.2 1.5 - 1.6 |
In the study of samples of suppositories with cocoa butter and lecithin in amount 5% proved that they can with stand loads from 1.9kg to 2.2kg and in amount 10% of lecithin with stand loads from 1.5kg to 1.6kg, respectively.
Thus, studies have shown that it is possible to produce suppository bases of cocoa butter with CSA, with МGD and lecithin in concentration 5% and 10% by casting method, which meet the requirements to suppository bases of SPhU 2.0.
A base with cocoa butter and 5% of lecithin showed the best results. Lecithin is a natural product and in the suppository base it acts as a thickener. Lecithin is a natural substance, namely phospholipids. Phospholipids are the main part of all cell membranes and organelles. They play a significant role in cellular metabolism, detoxification and cell regeneration. Lecithin is a component of the myelin sheaths of nerve cells and fibers, contributing to the transmission of neuromuscular impulse. Lecithin is recommended to be added to the suppository base if it is necessary to provide it emulsifying properties. The ratio of cocoa butter and lecithin is established experimentally.
The content of lecithin in bases is from 4.9 to 5.1%, depending on the amount and properties of medicinal substances that are incorporated into the base. The qualitative properties of the suppository base depend not only on the composition, but also from the method of the base preparation.
The cocoa butter base with lecithin is a natural origin. It is a combination of two substances provides the necessary structural and mechanical properties of the prepared suppositories for their application in proctological, urological and gynecological practice. Lecithin was added if necessary to render the properties of the thickener, sealant and emulsifier.
CONCLUSIONS:
Thus, the proposed suppository base of natural origin has the following advantages: the base is well tolerated and does not have osmotic pressure. Cocoa butter in combination with lecithin has a lubricating, moderate reparative. The investigated suppository bases are recommended by the authors for the introduction of various types of medicinal substances (thermolabile substances, volatile substances, enzymes and probiotics, substances with a high melting point, dense and liquid extracts).
CONFLICT OF INTEREST:
These authors declare that they have no conflict of interest.
REFERENCES:
1. State Pharmacopoeia of Ukraine. Scientifical Pharmacopoeia center, 2 App., Kh.: RІRЕG. 2015; Vol. 1:716-723.
2. Yarnykh TG, Tykhonov OI, Gryzodub OI, Chushenko VM, Levachkova Yu. Technology of rectal suppositories and pessaries “ex tempore” - proposals for the supplement of the general monograph of SPU 5.N.1 Ex tempore drugs. Pharmakom. 2010; 1:64-78.
3. State Pharmacopoeia of Ukraine: Suppositories and pessaries made in pharmacies. Scientifical Pharmacopoeia center. 2 App. Kh.: RІRЕG. 2014; 716-723.
4. Orlova TV, Pankrusheva TA. Choosing of Suppository Bases in Suppository Technology. Pharmacy. 2014; 1:34-38.
5. Tykhonov OI. Chemist’s technology of drugs, 4th edn, New Book, Vinnytsia. 2016.
6. Yarnykh TG, Tolochko KV, Chushenko VM. Study of the range of suppository bases (review). Chemical and Pharmaceutical Journal. 2010; 44(10):21-26.
7. European Pharmacopoeia, 5 th ed., Strasbourg, Council of Europe. 2005.
8. USP Pharmacists' Pharmacopeia, The United State Pharmacopeial, Inc., Rockville. 2008.
9. Yarnykh TG, Levachkova YuV, Buryak MV, Kubrina NV. Basics of Suppository Technology - Extemporal Preparation. Pharmacy. 2010; 2:54-56.
10. Yarnykh TG, Tolochko KV, Chushenko VM. Basis for suppositories. Patent for utility model № 69000 Ukraine, Public. 25.04.2012, Bul. № 8.
Received on 19.09.2019 Modified on 10.11.2019
Accepted on 21.12.2019 © RJPT All right reserved
Research J. Pharm. and Tech. 2020; 13(7): 3343-3346.
DOI: 10.5958/0974-360X.2020.00593.4