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SELECTION OF excipients AND ANALYSIS OF CRITICAL PARAMETERS OF THE TECHNOLOGICAL PROCESS OF PRODUCTION OF CAPSULES WITH ANTHELMINTIC
ACTIVITY
Semchenko K.
PhD of Pharmacy, Associate Professor of Department of Pharmaceutical Technology of Drugs, NUPh
Vyshnevska L.
Doctor of Pharmacy, Professor, Head of Department of Pharmaceutical Technology of Drugs, NUPh
Abstract
Pharmacotherapy of helminthiasis involves three main stages of treatment: preparatory (desensitization of the body), etiotropic treatment (destruction of the pathogen) and elimination of the consequences and complications of the disease.
After the helminthiasis, the patient needs to restore the normal functioning of the immune system, gastrointestinal tract, metabolism and so on. Therefore, an important task is to develop a drug for this stage of pharma-cotherapy of helminthiasis.
Herbal medicines are best suited for the recovery of the patient's body after an invasive disease.
To meet the needs of the population in phytomedicine for the 3rd stage of treatment of helminthiasis of the digestive system, we have proposed a drug based on a complex of extracts of medicinal plants. The composition has anthelmintic, antiparasitic, anti-inflammatory, antibacterial, antiseptic, hepatoprotective, nephroprotective, laxative, antiallergic, antispasmodic, analgesic, sedative activity and can be used to treat helminthiasis of the digestive system.
Keywords: helminthiasis, capsules, technology, plant raw material
Introduction.
Capsules (Latin "Capsula" - literally "case, box") are a solid dosage form with a soft or hard shell, containing a dose of one or more active substances [].
Extensive possibilities of prescribing drugs in the form of capsules have led to an increase in their production and consumption. Thus, abroad, among the dosed drugs of industrial production, capsules take the 3rd place after tablets and ampoules [1, 2].
Capsules show a fairly high level of bioavailabil-ity (on average, the therapeutic effect of the content is manifested in 5-10 min. after administration) and have a number of advantages: good appearance; easiness of usage (easy to swallow); gelatin shell is impermeable to volatile liquids, gases, oxygen (which is very important for the storage of products that are easily oxidized), it is convenient to place in a capsule of dyes and substances that have an unpleasant taste and odor. Also, the capsules are very promising for use in pediatrics and gerontology [1, 3, 4].
As in the technology of tablets, in the production of capsules an important parameter is the flowability of
the capsule mass, which ensures the accuracy of dosing and continuity of the capsule filling machine [3, 4].
It is known that to ensure fluidity the sliding (antifriction) substances are added, and to improve the ejection of the compressed mass from the dosing disks lubricants are introduced to the capsule mass, such as magnesium stearate.
The purpose of this work is the research on the selection of excipients to ensure the proper technological characteristics of the capsule mass.
Materials and methods. The research objects were the concentrate of the dry extract of medicinal plants (tansy flower dry extract, wormwood herb dry extract, centaury herb dry extract, wormwood flower dry extract, buckthorn bark dry extract, elecampane rhizomes with roots dry extract, dandelion herb with roots dry extract, chamomile flowers dry extract, ginger rhizome dry extract, valerian root dry extract), lactose, aerosol, talc, magnesium stearate and the model samples of the capsule mass on their basis.
Studies on determination of the composition and ratio of active ingredients are described earlier [5, 6].
Results. In order to establish the optimal compo- the properties of several samples of capsule masses sition and quantitative content of excipients, we studied (Table 1).
Table 1
The composition of the capsule mass with the addition of excipients
Composition of the capsule mass Quantitative content of ingredients, mass. %
Sample
1 2 3 4 5
Concentrate of the dry extract of medicinal plants 85.7 85.7 85.7 85.7 85.7
Lactose 13.8 5.8 10.8 6.8 5.8
Aerosil - 8.0 - 5.0 4.0
Talc - - 3.0 2.0 4.0
Magnesium stearate 0.5 0.5 0.5 0.5 0.5
Total: 100.0 100.0 100.0 100.0 100.0
Evaluation of the flowability of model samples of the capsule mass was performed by determining the angle of natural slope and flow rate through the nozzle (Table 2).
Table 2
Determination of the flowability of capsule mass samples
Indicator Sample
1 2 3 4 5
The angle of the natural slope, ° 38.5 40.0 42.0 31.5 385.5
± 0.5 ± 0.5 ± 0.5 ± 0.5 ± 0.5
Flow rate through the nozzle, kg / 0.0077 0.0059 0.0057 0.0129 0.0181
sec ± 0.0005 ± 0.0005 ± 0.0005 ± 0.0005 ± 0.0005
According to the obtained results (Table 2) of the natural slope angle (according to the yield scale and the corresponding slope angle of SPU1 2.1, table 2.9.36.-1) samples 1 and 5 have satisfactory flowability, samples 2 and 3 - allowable flowability), and sample 4 - good flowability. Samples 4 and 5 have the best flow rates through the nozzle.
For the established composition of capsules under the conditional name "Phytohelmin", the production technology was processed.
Description of the technological process of capsule production under the conditional name "Phytohelmin "
Based on the totality of the obtained results, the most rational is the sample of the capsule mass 4.
Thus, the final composition of the capsules for the 3rd stage of treatment of helminthiasis of the digestive system from the conditional name "Phytohelmin" is given in Table 3.
Table 3
In the production room for weighing (purity class D) on industrial scales or analytical scales the ingredients for one batch of the drug are weighed. Substances are prepared in portable containers. Stage 1. Weighing and sieving Tansy flower dry extract, wormwood herb dry extract, centaury herb dry extract, wormwood flower dry
The composition of the capsules "Phytohelmin"
Ingredient Quantity, mass.%
Tansy flower dry extract 12.7
Wormwood herb dry extract 12.7
Centaury herb dry extract 12.7
Wormwood flower dry extract 8.6
Buckthorn bark dry extract 8.6
Elecampane rhizomes with roots dry extract 8.6
Dandelion herb with roots dry extract 8.6
Ginger rhizome dry extract 4.4
Valerian root dry extract 4.4
Chamomile flowers dry extract 4.4
Lactose 6.8
Aerosil 5.0
Talk 2.0
Magnesiu. stearate 0.5
Total: 100.0
1 SPU - State Pharmacopoeia of Ukraine
extract, buckthorn bark dry extract, elecampane rhizomes with roots dry extract, dandelion herb with roots dry extract, chamomile flowers dry extract, ginger rhizome dry extract, valerian root dry extract, lactose, aer-osil, talc, magnesium stearate are weighed and sieved using a vibrating screen and transferred to stage 2.
Stage 2. Obtaining mass for encapsulation
The ingredients are loaded into the mixer to obtain a capsule mass and mix thoroughly until homogeneity.
The resulting mass for encapsulation is transferred to stage 3.
Stage 3. Encapsulation
With the help of a machine for filling of the hard capsules, the mass is encapsulated in hard gelatin capsules of size "0". An intermediate quality control is carried out and the capsules are transfer to stage 4.
Table 4
Critical parameters of the production process of capsules "Phytohelmin"
Stage Critical parameter Value of the critical parameter
2. Obtaining mass for encapsulation Mixing time Homogeneity of mixing 20-25 min Homogeneity
4. Packing of capsules in blisters Drum temperature, film quality and marking Compliance with technical standards of equipment operation
Stage 4. Packing of capsules in blisters Capsules from stage 3 are packed in blisters of the combined composition of PVC film and foil. Stage 5. Packing blisters in packs Blisters with capsules and instructions for medical use are placed in packs. An intermediate control is carried out.
Stage 6. Packing packs in boxes Packs are placed in group packaging boxes and control of finished products.
The possible critical parameters of the production process were established experimentally and are described in Table 4.
Discussion. Based on the findings carried out on the flowability characteristics of the samples of the capsule mass, it was found that the best flowability parameters are characteristic of sample 4: with 6.8 mass.% of lactose, 5.0 mass.% of aerosil, 2.0 mass.% of talc and 0.5 mass.% of magnesium stearate.
For the established composition of the capsules, the technological process of obtaining was described and the possible critical stages of production were established.
Conclusion. The selection of the excipients for the capsules under the conditional name "Phytohelmin" for the 3rd stage of treatment of helminthiasis of the digestive system is described.
The production process of the capsules "Phytohelmin" was described and the possible critical parameters were set.
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