CN106511286B - Famciclovir tablet with high stability and preparation method thereof - Google Patents
Famciclovir tablet with high stability and preparation method thereof Download PDFInfo
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- CN106511286B CN106511286B CN201610957436.9A CN201610957436A CN106511286B CN 106511286 B CN106511286 B CN 106511286B CN 201610957436 A CN201610957436 A CN 201610957436A CN 106511286 B CN106511286 B CN 106511286B
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- famciclovir
- tablet
- mannitol
- carboxymethyl starch
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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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
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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
Abstract
The invention provides a preparation method of famciclovir tablets with high stability, which comprises the following steps: (1) mixing famciclovir, mannitol, sodium carboxymethyl starch and sodium bicarbonate, wherein the weight ratio of famciclovir to mannitol to sodium carboxymethyl starch to sodium bicarbonate is 3-5:1-1.5:0.5-0.6: 0.8-1; (2) adding 2.8-3.5 wt% of carboxymethyl cellulose ethanol solution into the product obtained in the step (1), making soft material, sieving with a 14-mesh sieve, granulating, drying at 65-75 ℃, and grading with a 20-mesh sieve; (3) and (3) adding magnesium stearate and crospovidone into the product obtained in the step (2), and tabletting to obtain the tablet. The invention also provides famciclovir tablets prepared by the method. The famciclovir tablet obtained by the invention has high dissolution rate, and the dissolution rate can reach more than 99.2% in 5 min; less impurities, the total impurities are only 0.21-0.23%, and the single impurities are not more than 0.10%; the famciclovir tablet obtained by the invention has high stability under the condition of accelerated experiment, and the impurity content is not increased basically.
Description
Technical Field
The invention belongs to the technical field of pharmaceutical engineering, and particularly relates to a famciclovir tablet with high stability and a preparation method thereof.
Background
Famciclovir (Famciclovir) is a diethyl acyl ester of a 6-deoxy derivative of penciclovir (penciclovir) with the molecular formula C14H19N5O4Has good oral absorption and high bioavailability.
Famciclovir has good bioavailability and longer action time, has certain effect on hepatitis B virus besides resisting herpes virus, and is regarded as a first-line medicament for resisting hepatitis B virus.
At present, the prior art has certain research on famciclovir preparations, and mainly focuses on improving dissolution and reducing sticking during tabletting. For example, in the Chinese patent 201310432394.3, famciclovir tablets with dissolution rate of more than 99.1 percent in 5min are obtained by using water solution of famciclovir and sodium bicarbonate as a lubricant, so that the rapid dissolution of famciclovir is realized. Chinese patent 201310430095.6 solves the problem of process stability during the process of tablet production by selecting auxiliary materials.
However, the long-term stability of famciclovir tablets is rarely studied in the prior art, which results in the existing famciclovir tablets having high impurity content and being not storage-resistant.
Therefore, there is a need in the art for a process for the preparation of famciclovir tablets that reduces impurities and improves storage stability.
Disclosure of Invention
In view of the disadvantages of the prior art, the present invention aims to provide a method for preparing famciclovir tablets with high stability, which comprises the following steps:
(1) mixing famciclovir, mannitol, sodium carboxymethyl starch and sodium bicarbonate, wherein the weight ratio of famciclovir to mannitol to sodium carboxymethyl starch to sodium bicarbonate is 3-5:1-1.5:0.5-0.6: 0.8-1;
(2) adding 2.8-3.5 wt% hydroxypropyl methylcellulose ethanol solution into the product obtained in step (1), making into soft material, sieving with 14 mesh sieve, granulating, oven drying at 65-75 deg.C, and sieving with 20 mesh sieve;
(3) and (3) adding magnesium stearate and crospovidone into the product obtained in the step (2), and tabletting to obtain the tablet.
Preferably, in the step (1), the weight ratio of famciclovir, mannitol, sodium carboxymethyl starch and sodium bicarbonate is 4.5-4.8:1.2-1.4:0.5-0.6: 0.8-1. More preferably, the weight ratio of famciclovir, mannitol, sodium carboxymethyl starch and sodium bicarbonate is 4.6:1.3:0.55: 0.85.
Preferably, the hydroxypropyl methylcellulose ethanol solution accounts for 3% by weight.
The addition amount of the magnesium stearate is 5-8% of the weight of famciclovir, and the addition amount of the crospovidone is 3-5% of the weight of famciclovir.
Preferably, the magnesium stearate is added in an amount of 6% by weight of famciclovir, and the crospovidone is added in an amount of 4% by weight of famciclovir.
Another object of the present invention is to provide famciclovir tablets prepared by the above preparation method.
The invention has the beneficial effects that:
(1) the famciclovir tablet obtained by the invention has high dissolution rate, and the dissolution rate can reach more than 99.2% in 5 min; less impurities, the total impurities are only 0.21-0.23%, and the single impurities are not more than 0.10%;
(2) the famciclovir tablet obtained by the invention has high stability under the condition of accelerated experiment, and the impurity content is not increased basically.
Detailed Description
The present invention is described in detail below by way of examples, and it should be noted that the following examples are only for illustrating the present invention and should not be construed as limiting the scope of the present invention.
Example 1
(1) Mixing famciclovir, mannitol, sodium carboxymethyl starch and sodium bicarbonate, wherein the weight ratio of famciclovir to mannitol to sodium carboxymethyl starch to sodium bicarbonate is 3:1:0.5: 0.8;
(2) adding 3.5 percent hydroxypropyl methylcellulose ethanol solution into the product obtained in the step (1) by weight percentage, preparing a soft material, sieving with a 14-mesh sieve for granulation, drying at 65-75 ℃, and then sieving with a 20-mesh sieve for granulation;
(3) and (3) adding magnesium stearate and crospovidone into the product obtained in the step (2), wherein the addition amount of the magnesium stearate is 5% of the weight of the famciclovir, and the addition amount of the crospovidone is 3% of the weight of the famciclovir, and tabletting to obtain the tablet.
Example 2
(1) Mixing famciclovir, mannitol, sodium carboxymethyl starch and sodium bicarbonate, wherein the weight ratio of famciclovir to mannitol to sodium carboxymethyl starch to sodium bicarbonate is 5:1.5:0.6: 1;
(2) adding 2.8 percent hydroxypropyl methylcellulose ethanol solution into the product obtained in the step (1) by weight percentage, preparing a soft material, sieving with a 14-mesh sieve for granulation, drying at 65-75 ℃, and then sieving with a 20-mesh sieve for granulation;
(3) and (3) adding magnesium stearate and crospovidone into the product obtained in the step (2), wherein the addition amount of the magnesium stearate is 8% of the weight of the famciclovir, and the addition amount of the crospovidone is 5% of the weight of the famciclovir, and tabletting to obtain the tablet.
Example 3
(1) Mixing famciclovir, mannitol, sodium carboxymethyl starch and sodium bicarbonate, wherein the weight ratio of famciclovir to mannitol to sodium carboxymethyl starch to sodium bicarbonate is 4.6:1.3:0.55: 0.85;
(2) adding a hydroxypropyl methylcellulose ethanol solution with the weight percentage of 3% into the obtained product in the step (1), preparing a soft material, sieving with a 14-mesh sieve for granulation, drying at 65-75 ℃, and then sieving with a 20-mesh sieve for granulation;
(3) and (3) adding magnesium stearate and crospovidone into the product obtained in the step (2), wherein the addition amount of the magnesium stearate is 6% of the weight of the famciclovir, and the addition amount of the crospovidone is 4% of the weight of the famciclovir, and tabletting to obtain the tablet.
Comparative example 1
The procedure is as in example 3 except that no sodium carboxymethyl starch is added.
Comparative example 2
Example 3 of chinese patent 201310432394.3.
Experimental example 1
The dissolution rates of the samples of examples 1 to 3 were measured by the method described in "Chinese pharmacopoeia" (2010 version). The results are shown in Table 1.
TABLE 1
Experimental example 2
The results of substance detection and accelerated test (40 ℃, 75% relative humidity, 6 months) for examples 1-3 and comparative examples 1-2 are shown in Table 2.
TABLE 2
Claims (2)
1. A method for preparing famciclovir tablets with high stability, which is characterized by comprising the following steps:
(1) mixing famciclovir, mannitol, sodium carboxymethyl starch and sodium bicarbonate, wherein the weight ratio of famciclovir to mannitol to sodium carboxymethyl starch to sodium bicarbonate is 4.6:1.3:0.55: 0.85;
(2) adding a hydroxypropyl methylcellulose ethanol solution with the weight percentage of 3% into the obtained product in the step (1), preparing a soft material, sieving with a 14-mesh sieve for granulation, drying at 65-75 ℃, and then sieving with a 20-mesh sieve for granulation;
(3) adding magnesium stearate and crospovidone into the product obtained in the step (2), and tabletting to obtain the tablet; the addition amount of the magnesium stearate is 6 percent of the weight of the famciclovir, and the addition amount of the crospovidone is 4 percent of the weight of the famciclovir;
the famciclovir tablet prepared by the preparation method has the total content of related substances of 0.21 percent at 0 month and 0.22 percent at 40 ℃ and 75 percent of relative humidity after being placed for 6 months.
2. Famciclovir tablets prepared according to the process of claim 1.
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| CN201610957436.9A CN106511286B (en) | 2016-10-27 | 2016-10-27 | Famciclovir tablet with high stability and preparation method thereof |
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| CN106511286B true CN106511286B (en) | 2019-12-20 |
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| CN112168829B (en) * | 2020-09-24 | 2022-02-15 | 华南理工大学 | Application of antiviral drug in preparation of drug for treating myelodysplastic syndrome and prepared myelodysplastic syndrome drug |
| CN112057430A (en) * | 2020-10-17 | 2020-12-11 | 迪沙药业集团有限公司 | Famciclovir pharmaceutical composition |
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| WO2007050631A2 (en) * | 2005-10-25 | 2007-05-03 | Cima Labs Inc. | Dosage form with coated active |
| CN101002781A (en) * | 2006-01-19 | 2007-07-25 | 上海秀新臣邦医药科技有限公司 | Tablets of vacyclovir hydrochloride, and its preparing method |
| CN101156856A (en) * | 2007-09-29 | 2008-04-09 | 刘全胜 | Falacyclovir dispersion piece and its preparation method |
| CN101904825A (en) * | 2010-07-29 | 2010-12-08 | 江苏晨牌药业有限公司 | Famciclovir dispersible tablet and preparation method thereof |
| CN103462926A (en) * | 2013-09-23 | 2013-12-25 | 南京正亮医药科技有限公司 | Famciclovir tablet and preparation method thereof |
| CN104434852A (en) * | 2013-09-18 | 2015-03-25 | 北京韩美药品有限公司 | Famciclovir direct compressed tablet and preparation method thereof |
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- 2016-10-27 CN CN201610957436.9A patent/CN106511286B/en active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007050631A2 (en) * | 2005-10-25 | 2007-05-03 | Cima Labs Inc. | Dosage form with coated active |
| CN101002781A (en) * | 2006-01-19 | 2007-07-25 | 上海秀新臣邦医药科技有限公司 | Tablets of vacyclovir hydrochloride, and its preparing method |
| CN101156856A (en) * | 2007-09-29 | 2008-04-09 | 刘全胜 | Falacyclovir dispersion piece and its preparation method |
| CN101904825A (en) * | 2010-07-29 | 2010-12-08 | 江苏晨牌药业有限公司 | Famciclovir dispersible tablet and preparation method thereof |
| CN104434852A (en) * | 2013-09-18 | 2015-03-25 | 北京韩美药品有限公司 | Famciclovir direct compressed tablet and preparation method thereof |
| CN103462926A (en) * | 2013-09-23 | 2013-12-25 | 南京正亮医药科技有限公司 | Famciclovir tablet and preparation method thereof |
Non-Patent Citations (1)
| Title |
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| 泛昔洛韦分散片稳定性的研究;张娟,等;《海峡药学》;20061231;第18卷(第4期);第31-32页 * |
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