CN106727357B - Acyclovir granules and preparation method thereof - Google Patents
Acyclovir granules and preparation method thereof Download PDFInfo
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- CN106727357B CN106727357B CN201710039374.8A CN201710039374A CN106727357B CN 106727357 B CN106727357 B CN 106727357B CN 201710039374 A CN201710039374 A CN 201710039374A CN 106727357 B CN106727357 B CN 106727357B
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1617—Organic compounds, e.g. phospholipids, fats
- A61K9/1623—Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/52—Purines, e.g. adenine
- A61K31/522—Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1641—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
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- Molecular Biology (AREA)
- Biophysics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses an acyclovir granule and a preparation method thereof, wherein the acyclovir granule comprises the following components: acyclovir: 50.0-200.0 parts; lactose: 762.0-912.0 parts; and (3) stevia: 5.0-8.0 parts; polyethylene glycol 6000 solution: 10.0-185.0 parts; wherein, in the polyethylene glycol 6000 solution, the content of effective components is 5.0-30.0 wt%, and the effect of improving the elution amount of the active components is achieved.
Description
Technical Field
The invention relates to an acyclovir preparation technology, in particular to acyclovir granules and a preparation method thereof.
Background
Acyclovir, also known as Acyclovir (ACV), is a nucleoside antiviral drug known by the chemical name 9- (2-hydroxyethoxymethyl) guanine. Acyclovir is an isoform of acyclic deoxyguanosine, which is a component of DNA, and is structurally similar to acyclovir, replacing the cyclic sugar structure with only an acyclic side chain.
Acyclovir was successfully developed in 1981 by the company Glanzin Vekang, England (Wellcome) and first marketed in the United kingdom under the trade name Zovirax; this product was approved by the FDA in the united states in 1982. Currently, acyclovir is one of the leading drugs sold worldwide. Acyclovir and its pharmaceutically acceptable salts and esters are known to have antiviral activity against various types of viruses both in vitro and in vivo. Specifically, acyclovir is active against the herpes viruses HSV1 (herpes simplex virus type 1), HSV2 (herpes simplex virus type 2), and VZV (varicella zoster virus), which are associated with a variety of infectious diseases in many species, particularly varicella, shingles in humans, and other skin and mucosal diseases in animals. Acyclovir has been shown to be effective in treating herpes simplex virus and herpes zoster virus infections in humans. It will be appreciated that reference herein to acyclovir also includes pharmaceutically acceptable salts and esters thereof.
Acyclovir suffers from the disadvantage that it is poorly water soluble and is almost completely insoluble in hydrophobic solvent systems, and therefore it is difficult to produce a topical formulation with sufficient dissolved concentration of the active ingredient to fully exert its efficacy.
Disclosure of Invention
A first object of the present invention is to provide acyclovir particles which solve the problem of low dissolution of active ingredients and have the effect of increasing the dissolution of active ingredients.
The technical purpose of the invention is realized by the following technical scheme:
the acyclovir granules comprise the following components in parts by mass:
acyclovir: 50.0-200.0 parts;
lactose: 762.0-912.0 parts;
and (3) stevia: 5.0-8.0 parts;
polyethylene glycol 6000 solution: 10.0-185.0 parts;
wherein, the content of effective components in the polyethylene glycol 6000 solution is 5.0-30.0 wt%.
By adopting the technical scheme, the lactose has certain fluidity, and can disperse the acyclovir and improve the fluidity of the granules so as to be beneficial to granulation; steviosin as correctant; the polyethylene glycol 6000 solution is beneficial to uniform dispersion in the wet granulation process, and can also increase the dissolution of effective components in acyclovir granules and enhance the effectiveness of acyclovir; the acyclovir granules are water-soluble granules, are dissolved in hot water, have sweet taste and good mouthfeel, and are convenient to take; and the granular form is safer.
More preferably: the paint comprises the following components in parts by weight:
acyclovir: 200.0 parts;
lactose: 762.0 parts of a binder;
and (3) stevia: 6.0 parts of (B);
15wt% polyethylene glycol 6000 solution: 32.0 parts.
More preferably: the paint comprises the following components in parts by weight:
acyclovir: 50.0 parts of a stabilizer;
lactose: 912.0 parts of a binder;
and (3) stevia: 6.0 parts of (B);
15wt% polyethylene glycol 6000 solution: 32.0 parts.
More preferably: the paint comprises the following components in parts by weight:
acyclovir: 100.0 parts;
lactose: 837.0 parts of a binder;
and (3) stevia: 6.0 parts of (B);
15wt% polyethylene glycol 6000 solution: 57.0 parts.
The second purpose of the invention is to provide a preparation method of acyclovir particles.
A preparation method of acyclovir particles comprises the following steps:
(1) preparing materials: respectively weighing acyclovir, lactose and steviosin according to the formula amount;
(2) and (3) granulating: uniformly mixing the raw materials in the step (1), adding a polyethylene glycol 6000 solution with a formula amount, uniformly mixing to prepare a soft material, and preparing the soft material into wet granules;
(3) and (3) post-treatment: and (3) drying, granulating, grading, sieving and subpackaging the wet granules obtained in the step (2) in sequence.
By adopting the technical scheme, the wet granulation is favorable for uniform dispersion, and the particle size, the water content, the morphology and the like of the wet granules obtained by the wet granulation can be strictly controlled after the wet granules are dried, granulated and sieved in a grading way, so that the difference among granule batches is reduced.
More preferably: in the step (1), the selected acyclovir, lactose and steviosin have the granularity of 80-500 meshes.
By adopting the technical scheme, the particle size difference is small, and the mixture is uniform; the granularity is controlled to be 80-500 meshes, and the high-performance liquid is favorable for being rapidly dispersed in a polyethylene glycol 6000 solution.
More preferably: in the step (3), the drying temperature is 50-90 ℃, and the drying time is 0.2-2 hr.
By adopting the technical scheme, the drying temperature is too low or the drying time is too short, so that the particles still contain considerable moisture, the subsequent treatment is influenced, and bacteria are easy to breed; if the drying temperature is too high or the drying time is too long, the bonding force between the particles is too small, the particles are loose, and the subsequent particle sizing and grading sieving are affected.
More preferably: in the step (3), the diameter of a screen used for straightening granules is 2-3.0 mm.
By adopting the technical scheme, if the diameter of the screen is too small, particles are difficult to fall and are easy to adhere to the screen to cause screen blockage; if the diameter of the screen is too large, the diameter of the particles obtained by the oversize granulation becomes large, and the dissolution rate is affected, thereby decreasing the precipitation rate of the active ingredient.
More preferably: in the step (3), the step of screening comprises sequentially passing through a first screen and a second screen, wherein the first screen is a 10-20-mesh screen, and the second screen is a 50-100-mesh screen; the granules which are sieved by the first sieve and are not sieved by the second sieve are selected for grading sieving.
By adopting the technical scheme and the grading and sieving treatment, if the granules are too large, the dissolution speed is influenced, and if the granules are too small, the difference among the granules is large, so that the quality difference among different granules cannot be reduced.
In conclusion, the invention has the following beneficial effects:
1. the acyclovir particles are antiviral drugs, and are low in toxicity, small in side effect, high in safety, low in price and good in effect;
2. the acyclovir granules are water-soluble granules, are dissolved in hot water, have sweet taste and good mouthfeel, are convenient to take, and are suitable for various crowds such as children and the old;
3. the granular form of the injection achieves the same drug effect level as an injection, and has less side effect and higher safety compared with the injection.
Detailed Description
The present embodiment is only for explaining the present invention, and it is not limited to the present invention, and those skilled in the art can make modifications of the present embodiment without inventive contribution as needed after reading the present specification, but all of them are protected by patent law within the scope of the present invention.
Example 1: acyclovir granules prepared by the following method:
(1) preparing materials: respectively weighing acyclovir, lactose and stevioside according to the formula, wherein the granularity of the acyclovir, the lactose and the stevioside is 80-500 meshes;
(2) and (3) granulating: putting the raw and auxiliary materials into a wet granulator, uniformly mixing, adding the polyethylene glycol 6000 solution with the formula amount, uniformly mixing to prepare soft materials, and then putting the soft materials into a swing granulator to prepare wet granules;
(3) and (3) post-treatment:
and (3) drying: putting the wet granules into a drier or an oven, and drying at 50-90 ℃ for 0.2-2 hr;
straightening: putting the dried particles into a granulating machine for granulating, wherein the diameter of a screen used for granulating is 2-3.0 mm;
grading and sieving: sequentially screening the whole particles by a first screen (namely a 10-20-mesh screen) and a second screen (namely a 50-100-mesh screen), collecting the particles which pass through the first screen but do not pass through the second screen, and keeping the particle size uniform;
subpackaging: subpackaging the granules with uniform thickness by a granule subpackaging and packaging machine, wherein each bag contains 1g of granules;
the formulation of example 1 is shown in table 1.
Table 1 formulation of example 1
| Raw and auxiliary materials | Dosage (mass fraction) |
| Acyclovir | 200.0 parts (folded into free state) |
| Lactose | 762.0 parts |
| Stevia rebaudianum extract | 6.0 parts of |
| 15wt% polyethylene glycol 6000 solution | 32.0 parts of |
Example 2: acyclovir granules, different from example 1 in that the formulation of example 2 is shown in table 2.
Table 2 formulation of example 2
| Raw and auxiliary materials | Dosage (mass fraction) |
| Acyclovir | 500.0 parts (folded into free state) |
| Lactose | 912.0 parts |
| Stevia rebaudianum extract | 6.0 parts of |
| 15wt% polyethylene glycol 6000 solution | 32.0 parts of |
Example 3: acyclovir granules, different from example 1, are formulated as shown in table 3 in example 3.
Table 3 formulation of example 3
| Raw and auxiliary materials | Dosage (mass fraction) |
| Acyclovir | 100.0 parts (folded into free state) |
| Lactose | 837.0 parts |
| Stevia rebaudianum extract | 6.0 parts of |
| 15wt% polyethylene glycol 6000 solution | 57.0 parts of |
Example 4: acyclovir granules, different from example 1, are formulated as shown in table 4 in example 4.
Table 4 formulation of example 4
| Raw and auxiliary materials | Dosage (mass fraction) |
| Acyclovir | 200.0 parts (folded into free state) |
| Lactose | 762.0 parts |
| Stevia rebaudianum extract | 5.0 parts of |
| 15wt% polyethylene glycol 6000 solution | 33.0 parts of |
Example 5: acyclovir granules, different from example 1, are formulated as shown in table 5 in example 5.
Table 5 formulation of example 5
| Raw and auxiliary materials | Dosage (mass fraction) |
| Acyclovir | 200.0 parts (folded into free state) |
| Lactose | 762.0 parts |
| Stevia rebaudianum extract | 8.0 parts of |
| 15wt% polyethylene glycol 6000 solution | 30.0 parts of |
Example 6: acyclovir granules, different from example 1 in that the effective component content of the polyethylene glycol 6000 solution was 5.0 wt%.
Example 7: acyclovir granules, different from example 1 in that the effective component content of the polyethylene glycol 6000 solution is 30.0 wt%.
Example 8: the acyclovir granules are different from the acyclovir granules in the embodiment 1 in that the granularity of the selected acyclovir, lactose and stevioside in the step (1) is 10-50 meshes; the mixing time is long and the effect is poor in the process of the step (2).
Example 9: acyclovir granules, different from example 1 in that, in step (3), the drying temperature is 40 ℃ and the drying time is 0.1 hr; wall sticking occurs during the post-treatment process.
Example 10: acyclovir granules, different from example 1 in that, in step (3), the drying temperature is 100 ℃ and the drying time is 3 hr; particle breakage occurs during the post-treatment process.
Example 11: acyclovir granules, different from example 1 in that in step (3), the diameter of the mesh used for size stabilization was 5.0 mm.
Example 12: acyclovir granules, different from example 1 in that in step (3), the diameter of the screen used for size stabilization was 0.5 mm; the screen blockage is obvious in the process.
Example 13: acyclovir granules, different from example 1 in that in step (3), the first sieve is a 5-mesh sieve, and the second sieve is a 200-mesh sieve; the particles are not uniformly dispersed.
Example 14: the acyclovir particles are different from those in example 1 in that in the step (3), the acyclovir particles only pass through a first sieve (i.e. a sieve with 10-20 meshes), and the particles passing through the first sieve are taken as subpackaging raw materials.
Example 15: acyclovir granules, different from example 1 in that, in step (3), there is no step of classification screening, i.e. the granules after size stabilization are directly used for subpackage; the particles are not uniformly dispersed.
Dissolution testing: the acyclovir granules of examples 1-7, 11 and 14 were taken and tested for dissolution after stirring in water at 25 deg.C, 37 deg.C and 60 deg.C for 1min, and the test results are shown in Table 6.
Table 6 dissolution rate test results
Claims (4)
1. The acyclovir granules are characterized by comprising the following components in percentage by mass:
acyclovir: 50.0-200.0 parts;
lactose: 762.0-912.0 parts;
and (3) stevia: 5.0-8.0 parts;
polyethylene glycol 6000 solution: 10.0-185.0 parts;
wherein, the content of effective components in the polyethylene glycol 6000 solution is 15 wt%;
the acyclovir granules are prepared by the following steps:
(1) preparing materials: respectively weighing acyclovir, lactose and stevioside according to the formula ratio, wherein the granularity of the selected acyclovir, lactose and stevioside is 80-500 meshes;
(2) and (3) granulating: uniformly mixing the raw materials in the step (1), adding a polyethylene glycol 6000 solution with a formula amount, uniformly mixing to prepare a soft material, and preparing the soft material into wet granules;
(3) and (3) post-treatment: drying, granulating, grading, sieving and subpackaging the wet granules obtained in the step (2), wherein the grading sieving comprises a first sieve and a second sieve in sequence, the first sieve is a sieve with 10-20 meshes, and the second sieve is a sieve with 50-100 meshes; and selecting the granules which are sieved by the first sieve and are not sieved by the second sieve during grading sieving, wherein the drying temperature is 50-90 ℃, the drying time is 0.2-2 hr, and the diameter of a sieve used for grading is 2-3.0 mm.
2. Acyclovir granules according to claim 1, comprising the following components in parts by weight:
acyclovir: 200.0 parts;
lactose: 762.0 parts of a binder;
and (3) stevia: 6.0 parts of (B);
15wt% polyethylene glycol 6000 solution: 32.0 parts.
3. Acyclovir granules according to claim 1, comprising the following components in parts by weight:
acyclovir: 50.0 parts of a stabilizer;
lactose: 912.0 parts of a binder;
and (3) stevia: 6.0 parts of (B);
15wt% polyethylene glycol 6000 solution: 32.0 parts.
4. Acyclovir granules according to claim 1, comprising the following components in parts by weight:
acyclovir: 100.0 parts;
lactose: 837.0 parts of a binder;
and (3) stevia: 6.0 parts of (B);
15wt% polyethylene glycol 6000 solution: 57.0 parts.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201710039374.8A CN106727357B (en) | 2017-01-19 | 2017-01-19 | Acyclovir granules and preparation method thereof |
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| CN201710039374.8A CN106727357B (en) | 2017-01-19 | 2017-01-19 | Acyclovir granules and preparation method thereof |
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| CN106727357B true CN106727357B (en) | 2020-09-18 |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007054976A2 (en) * | 2005-11-08 | 2007-05-18 | Panacea Biotec Ltd. | Lipid based controlled release pharmaceutical composition |
| WO2008140459A1 (en) * | 2007-05-16 | 2008-11-20 | Fmc Corporation | Solid form |
| CN101502521A (en) * | 2008-09-04 | 2009-08-12 | 山东淄博新达制药有限公司 | Acyclovir sustained-release preparation composition and method for preparing the same |
| CN101502520A (en) * | 2008-09-04 | 2009-08-12 | 山东淄博新达制药有限公司 | Acyclovir enteric-coated formulation composition and method for preparing the same |
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2017
- 2017-01-19 CN CN201710039374.8A patent/CN106727357B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007054976A2 (en) * | 2005-11-08 | 2007-05-18 | Panacea Biotec Ltd. | Lipid based controlled release pharmaceutical composition |
| WO2008140459A1 (en) * | 2007-05-16 | 2008-11-20 | Fmc Corporation | Solid form |
| CN101502521A (en) * | 2008-09-04 | 2009-08-12 | 山东淄博新达制药有限公司 | Acyclovir sustained-release preparation composition and method for preparing the same |
| CN101502520A (en) * | 2008-09-04 | 2009-08-12 | 山东淄博新达制药有限公司 | Acyclovir enteric-coated formulation composition and method for preparing the same |
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Address after: 311199 Nanyuan street, Yuhang District, Zhejiang, Jiangsu Province, Su Village (security bridge) Applicant after: Hangzhou Yipin Jiuzhitang Pharmaceutical Co. Ltd. Address before: 311100 Sujia village, Nanyuan street, Yuhang District, Hangzhou City, Zhejiang province (security bridge) Applicant before: Hangzhou Huadong medicine group Jiuzhitang Pharmaceutical Co. Ltd. |
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