CN115569935A - Pipeline cleaning process and preparation method of olopatadine hydrochloride eye drops based on pipeline cleaning process - Google Patents
Pipeline cleaning process and preparation method of olopatadine hydrochloride eye drops based on pipeline cleaning process Download PDFInfo
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- CN115569935A CN115569935A CN202211176254.XA CN202211176254A CN115569935A CN 115569935 A CN115569935 A CN 115569935A CN 202211176254 A CN202211176254 A CN 202211176254A CN 115569935 A CN115569935 A CN 115569935A
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- benzalkonium chloride
- eye drops
- olopatadine hydrochloride
- cleaning process
- filter element
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- 239000003889 eye drop Substances 0.000 title claims abstract description 45
- 229940012356 eye drops Drugs 0.000 title claims abstract description 39
- HVRLZEKDTUEKQH-NOILCQHBSA-N Olopatadine hydrochloride Chemical compound Cl.C1OC2=CC=C(CC(O)=O)C=C2C(=C/CCN(C)C)\C2=CC=CC=C21 HVRLZEKDTUEKQH-NOILCQHBSA-N 0.000 title claims abstract description 36
- 229960003139 olopatadine hydrochloride Drugs 0.000 title claims abstract description 36
- 238000000034 method Methods 0.000 title claims abstract description 32
- 238000004140 cleaning Methods 0.000 title claims abstract description 28
- 238000002360 preparation method Methods 0.000 title claims abstract description 22
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 claims abstract description 58
- 229960000686 benzalkonium chloride Drugs 0.000 claims abstract description 56
- 239000000243 solution Substances 0.000 claims abstract description 38
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 37
- 238000011010 flushing procedure Methods 0.000 claims abstract description 28
- 239000007788 liquid Substances 0.000 claims abstract description 14
- 238000001914 filtration Methods 0.000 claims abstract description 13
- 239000002699 waste material Substances 0.000 claims abstract description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical group Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 20
- 239000000022 bacteriostatic agent Substances 0.000 claims description 20
- 239000007924 injection Substances 0.000 claims description 18
- 238000002347 injection Methods 0.000 claims description 18
- 230000003204 osmotic effect Effects 0.000 claims description 15
- 238000002156 mixing Methods 0.000 claims description 11
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical group [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 10
- 238000003756 stirring Methods 0.000 claims description 10
- 239000006172 buffering agent Substances 0.000 claims description 9
- 239000008215 water for injection Substances 0.000 claims description 7
- 239000000872 buffer Substances 0.000 claims description 6
- 239000004695 Polyether sulfone Substances 0.000 claims description 5
- 238000001816 cooling Methods 0.000 claims description 5
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical group [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 claims description 5
- 229920001684 low density polyethylene Polymers 0.000 claims description 5
- 239000004702 low-density polyethylene Substances 0.000 claims description 5
- 239000012528 membrane Substances 0.000 claims description 5
- 229920006393 polyether sulfone Polymers 0.000 claims description 5
- 239000011780 sodium chloride Substances 0.000 claims description 5
- 229910001220 stainless steel Inorganic materials 0.000 claims description 5
- 239000010935 stainless steel Substances 0.000 claims description 5
- 238000005303 weighing Methods 0.000 claims description 5
- 239000000203 mixture Substances 0.000 claims description 3
- 238000009738 saturating Methods 0.000 claims description 2
- 238000005406 washing Methods 0.000 claims 2
- 238000000079 presaturation Methods 0.000 abstract description 11
- 238000004519 manufacturing process Methods 0.000 abstract description 6
- 238000001179 sorption measurement Methods 0.000 abstract description 5
- 238000012797 qualification Methods 0.000 abstract description 4
- 230000000052 comparative effect Effects 0.000 description 4
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B08—CLEANING
- B08B—CLEANING IN GENERAL; PREVENTION OF FOULING IN GENERAL
- B08B9/00—Cleaning hollow articles by methods or apparatus specially adapted thereto
- B08B9/02—Cleaning pipes or tubes or systems of pipes or tubes
- B08B9/027—Cleaning the internal surfaces; Removal of blockages
- B08B9/032—Cleaning the internal surfaces; Removal of blockages by the mechanical action of a moving fluid, e.g. by flushing
-
- 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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
- A61K47/186—Quaternary ammonium compounds, e.g. benzalkonium chloride or cetrimide
-
- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0048—Eye, e.g. artificial tears
-
- 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
- A61K9/08—Solutions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Ophthalmology & Optometry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Mechanical Engineering (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicinal Preparation (AREA)
- Medical Preparation Storing Or Oral Administration Devices (AREA)
Abstract
The invention discloses a pipeline cleaning process for filtering a circulating pipeline and a filter element for preparing olopatadine hydrochloride eye drops, which comprises the following steps: circularly flushing the pipeline and the filter element by 0.003 percent benzalkonium chloride solution, and discarding the waste liquid, wherein the flushing time is 40min, and the flow rate of the benzalkonium chloride solution during flushing is 0.55m/s. After 0.003 percent benzalkonium chloride solution presaturation flushing liquid is used for draining, the residual quantity of benzalkonium chloride has no obvious influence on the preparation of the olopatadine hydrochloride eye drops, so the benzalkonium chloride solution presaturation circulating pipeline and the filter element are adopted before the liquid preparation, the adsorption rate of the benzalkonium chloride on the circulating water pipe and the filter element is reduced, the qualification rate of the eye drops is ensured, and the influence on the production of the follow-up batch of eye drops is avoided.
Description
Technical Field
The invention relates to the technical field of eye drop preparation, in particular to a pipeline cleaning process and a preparation method of olopatadine hydrochloride eye drops based on the pipeline cleaning process.
Background
When the olopatadine hydrochloride eye drops are prepared, benzalkonium chloride is needed, but the benzalkonium chloride has certain adsorbability and can be adhered to a circulating pipeline and a filter element of equipment, so that the qualification rate of the olopatadine hydrochloride eye drops can be influenced, and the production and preparation of the subsequent batches of eye drops can be influenced due to the fact that the benzalkonium chloride is remained on the circulating pipeline and the filter element. At present, a large amount of clear water is mostly adopted to clean a circulating pipeline and a filter element so as to solve the problem of adsorption of benzalkonium chloride, but the removal mode cannot achieve the expected removal effect, also causes waste of water resources and still has the risk of not meeting the requirements of cleaning and filtering; meanwhile, the adsorption rate of benzalkonium chloride in the process of preparing the solution cannot be reduced.
Disclosure of Invention
The invention aims to provide a pipeline cleaning process and a preparation method of olopatadine hydrochloride eye drops based on the pipeline cleaning process, which are used for solving the technical problems in the background technology.
The technical scheme of the invention provides a pipeline cleaning process for filtering a circulating pipeline and a filter element for preparing olopatadine hydrochloride eye drops, wherein the cleaning process comprises the following steps: circularly flushing the pipeline and the filter element by using benzalkonium chloride solution with the mass fraction of 0.002-0.003 percent, discarding the waste liquid, wherein the flushing time is 35-50min, and the flow speed of the benzalkonium chloride solution during flushing is 0.5-0.7m/s.
In a preferred embodiment, the mass fraction of benzalkonium chloride in the benzalkonium chloride solution is equal to 0.003%, the rinsing time is 40min, and the flow rate of the benzalkonium chloride solution during rinsing is 0.55m/s.
A preparation method of olopatadine hydrochloride eye drops comprises the following steps:
s1: flushing the pipeline and the filter element through any pipeline cleaning process to carry out pre-saturation treatment;
s2: weighing the following components in parts by weight: 0.5-0.8 part of olopatadine hydrochloride, 0.9-1.3 parts of buffering agent, 0.8-1.3 parts of osmotic pressure regulator, 0.04-0.07 part of bacteriostatic agent, a proper amount of pH regulator and 120-130 parts of water for injection.
S3: adding 50% of the prescribed amount of injection water into a dosing tank, cooling to 45 +/-5 ℃ for standby, adding a weighed buffering agent and an osmotic pressure regulator into the dosing tank, pouring a weighed bacteriostatic agent into a stainless steel barrel, adding a proper amount of injection water for dissolving, pouring the bacteriostatic agent into the dosing tank, stirring and dispersing for 40-60min, and adding the injection water to 80% of the prescribed amount;
s4: adjusting pH of the solution to 6.5 + -0.2 with pH regulator, adding the rest injectable water to desired volume, stirring for 10-15min, and mixing;
s5: filtering the solution with constant volume by sequentially passing through polyethersulfone filter membranes with the aperture of 0.45 mu m and the aperture of 0.22 mu m;
s6: the mixture is filled in a low-density polyethylene medicinal eye drop bottle, and the concentration is 5 mg/bottle.
In a preferred embodiment, the buffer is disodium hydrogen phosphate, the osmotic pressure regulator is sodium chloride, the bacteriostatic agent is benzalkonium chloride, the pH regulator is hydrochloric acid, and the concentration of the hydrochloric acid is 1mol/L.
In a preferred embodiment, the content of olopatadine hydrochloride in 100mL of eye drops is 0.08-0.09g.
The technical scheme of the invention has the beneficial effects that:
after the benzalkonium chloride is used for pre-saturating a pipeline and a filter element, the content of the benzalkonium chloride in the prepared olopatadine hydrochloride eye drops is obviously higher than that of a prescription which is washed by clear water and then filtered, and the prepared olopatadine hydrochloride eye drops meet the standard requirement of 0.024mg/ml-0.036mg/ml of benzalkonium chloride of the product.
After 0.003 percent benzalkonium chloride solution presaturation flushing fluid is used for draining, the benzalkonium chloride residual quantity has no obvious influence on the preparation of the olopatadine hydrochloride eye drops, so that a benzalkonium chloride solution presaturation circulating pipeline and a filter core are adopted before the preparation of the eye drops, the adsorption rate of benzalkonium chloride on a circulating water pipe and the filter core is reduced, the qualification rate of the eye drops is ensured, and the influence on the production of the follow-up batches of the eye drops is avoided.
Detailed Description
The present invention will be described in further detail with reference to specific embodiments. The embodiments of the present invention have been presented for purposes of illustration and description, and are not intended to be exhaustive or limited to the invention in the form disclosed. Many modifications and variations will be apparent to those of ordinary skill in the art. The embodiment was chosen and described in order to best explain the principles of the invention and the practical application, and to enable others of ordinary skill in the art to understand the invention for various embodiments with various modifications as are suited to the particular use contemplated.
Example 1
The technical scheme of the invention provides a pipeline cleaning process for filtering a circulating pipeline and a filter element for preparing olopatadine hydrochloride eye drops, wherein the cleaning process comprises the following steps: circularly flushing the pipeline and the filter element by 0.002 percent benzalkonium chloride solution by mass percent, and discarding the waste liquid, wherein the flushing time is 35min, and the flow rate of the benzalkonium chloride solution during flushing is 0.7m/s.
A preparation method of olopatadine hydrochloride eye drops comprises the pipeline cleaning process, and comprises the following steps:
s1: carrying out presaturation treatment through a benzalkonium chloride solution circulating flushing pipeline and a filter element;
s2: weighing the following components in parts by weight: olopatadine hydrochloride 0.5 part, buffer 0.9 part, osmotic pressure regulator 0.8 part, bacteriostatic agent 0.04 part, proper amount of pH regulator and injection water 120 parts.
S3: adding 50% of injection water according to the prescription amount into a dosing tank, cooling to 45 +/-5 ℃ for standby application, adding a weighed buffering agent and an osmotic pressure regulator into the dosing tank, pouring a weighed bacteriostatic agent into a stainless steel barrel, adding a proper amount of injection water for dissolving, pouring the bacteriostatic agent into the dosing tank, stirring and dispersing for 40min, and adding the injection water to 80% of the prescription amount;
s4: adjusting the pH value of the solution to 6.3 by using a pH regulator, adding the rest of water for injection to constant volume, stirring for 10min, and uniformly mixing;
s5: filtering the solution with constant volume by sequentially passing through polyethersulfone filter membranes with the aperture of 0.45 mu m and the aperture of 0.22 mu m;
s6: the mixture is filled in a low-density polyethylene medicinal eye drop bottle, and the concentration is 5 mg/bottle.
The buffer is disodium hydrogen phosphate, the osmotic pressure regulator is sodium chloride, the bacteriostatic agent is benzalkonium chloride, the pH regulator is hydrochloric acid, and the concentration of the hydrochloric acid is 1mol/L.
The content of olopatadine hydrochloride in 100mL eye drops is 0.08-0.09g.
Example 2
The technical scheme of the invention provides a pipeline cleaning process for filtering a circulating pipeline and a filter element for preparing olopatadine hydrochloride eye drops, wherein the cleaning process comprises the following steps: circularly flushing the pipeline and the filter element by 0.003 percent benzalkonium chloride solution, and discarding the waste liquid, wherein the flushing time is 50min, and the flow rate of the benzalkonium chloride solution during flushing is 0.5m/s.
A preparation method of olopatadine hydrochloride eye drops comprises the pipeline cleaning process, and comprises the following steps:
s1: pre-saturation treatment is carried out through a benzalkonium chloride solution circulating flushing pipeline and a filter element;
s2: weighing the following components in parts by weight: olopatadine hydrochloride 0.8 part, buffering agent 1.3 parts, osmotic pressure regulator 1.3 parts, bacteriostatic agent 0.07 part, proper amount of pH regulator and injection water 130 parts.
S3: adding 50% of the prescription amount of injection water into a mixing tank, cooling to 45 +/-5 ℃ for later use, adding a weighed buffering agent and an osmotic pressure regulator into the mixing tank, pouring a weighed bacteriostatic agent into a stainless steel barrel, adding a proper amount of injection water for dissolving, then pouring the bacteriostatic agent into the mixing tank, stirring and dispersing for 60min, and adding the injection water to 80% of the prescription amount;
s4: adjusting the pH value of the solution to 6.7 by using a pH regulator, adding the rest of water for injection to constant volume, stirring for 15min, and uniformly mixing;
s5: filtering the solution with constant volume by sequentially passing through polyethersulfone filter membranes with the aperture of 0.45 mu m and the aperture of 0.22 mu m;
s6: the low-density polyethylene medical eye drop bottle is filled, and the volume is 5 mg/bottle.
The buffer is disodium hydrogen phosphate, the osmotic pressure regulator is sodium chloride, the bacteriostatic agent is benzalkonium chloride, the pH regulator is hydrochloric acid, and the concentration of the hydrochloric acid is 1mol/L.
The content of olopatadine hydrochloride in 100mL eye drops is 0.08-0.09g.
Example 3
The technical scheme of the invention provides a pipeline cleaning process for filtering a circulating pipeline and a filter element for preparing olopatadine hydrochloride eye drops, wherein the cleaning process comprises the following steps: circularly flushing the pipeline and the filter element by using 0.025 mass percent benzalkonium chloride solution, and discarding the waste liquid, wherein the flushing time is 40min, and the flow rate of the benzalkonium chloride solution during flushing is 0.55m/s.
A preparation method of olopatadine hydrochloride eye drops comprises the pipeline cleaning process, and comprises the following steps:
s1: carrying out presaturation treatment through a benzalkonium chloride solution circulating flushing pipeline and a filter element;
s2: weighing the following components in parts by weight: 0.6 part of olopatadine hydrochloride, 0.9-1.3 parts of buffering agent, 0.9 part of osmotic pressure regulator, 0.06 part of bacteriostatic agent, a proper amount of pH regulator and 130 parts of water for injection.
S3: adding 50% of injection water according to the prescription amount into a dosing tank, cooling to 45 +/-5 ℃ for standby application, adding a weighed buffering agent and an osmotic pressure regulator into the dosing tank, pouring a weighed bacteriostatic agent into a stainless steel barrel, adding a proper amount of injection water for dissolving, pouring the bacteriostatic agent into the dosing tank, stirring and dispersing for 50min, and adding the injection water to 80% of the prescription amount;
s4: adjusting the pH value of the solution to 6.7 by using a pH regulator, adding the rest of water for injection to constant volume, stirring for 15min, and uniformly mixing;
s5: filtering the solution with constant volume by sequentially passing through polyethersulfone filter membranes with the aperture of 0.45 mu m and the aperture of 0.22 mu m;
s6: the low-density polyethylene medical eye drop bottle is filled, and the volume is 5 mg/bottle.
The buffer is disodium hydrogen phosphate, the osmotic pressure regulator is sodium chloride, the bacteriostatic agent is benzalkonium chloride, the pH regulator is hydrochloric acid, and the concentration of the hydrochloric acid is 1mol/L.
The content of olopatadine hydrochloride in 100mL eye drops is 0.08-0.09g.
Using the same cleaning process and preparation protocol of example 1, two sets of comparative examples were obtained with benzalkonium chloride concentrations varying only during the cleaning process, the benzalkonium chloride concentration of comparative example 1 being 0.001% and the benzalkonium chloride concentration of comparative example 2 being 0.004%.
The following tests were carried out, taking examples 1-2, comparative examples 1-2, and direct rinsing with clear water as examples:
1. the pipeline and the filter element before liquid preparation are cleaned respectively by adopting the following two modes: (1) Before liquid preparation, the water pipe is flushed by clean water, and filtering is carried out in the liquid preparation process (after the middle large circulation step); (2) The benzalkonium chloride content in the prepared solution obtained by the two methods is shown in the following table 1:
TABLE 1
As can be seen from Table 1, after the benzalkonium chloride with the concentration of 0.002% -0.003% is adopted to carry out pre-saturation treatment on the pipeline filter element, the content of the benzalkonium chloride in the prepared olopatadine hydrochloride eye drops is obviously higher than that of the prescription which is washed by clear water and then filtered, the olopatadine hydrochloride eye drops meet the standard requirement of 0.024mg/ml-0.036mg/ml of the benzalkonium chloride of the product, and the best concentration of 0.003% is selected.
2. Considering that benzalkonium chloride residue may affect production batches, and combining the dissolution property of benzalkonium chloride, taking a 0.003% benzalkonium chloride solution as an example, 4 times of flushing are performed on the circulation pipeline and the filter element after liquid preparation by using water for injection, and the total benzalkonium chloride residue is calculated as shown in table 2 below:
TABLE 2
As can be seen from Table 2, the total residual amount of benzalkonium chloride is only about 2.5% of the amount prescribed, and considering that the actual production residual situation is far less than that of the injection water for flushing, after the 0.003% benzalkonium chloride solution presaturation flushing liquid is used for draining, the residual amount of benzalkonium chloride has no obvious influence on the preparation of olopatadine hydrochloride eye drops, so that a benzalkonium chloride solution presaturation circulating pipeline and a filter element are adopted before the liquid preparation, the adsorption rate of benzalkonium chloride on the circulating water pipe and the filter element is reduced, the qualification rate of the eye drops is ensured, and the influence on the production of the follow-up batch of eye drops is avoided.
It is to be understood that the described embodiments are merely a few embodiments of the invention, and not all embodiments. All other embodiments, which can be derived by one of ordinary skill in the art and related arts based on the embodiments of the present invention without any creative effort, shall fall within the protection scope of the present invention. Structures, devices, and methods of operation not specifically described or illustrated herein are not specifically illustrated or described, but are instead contemplated to be practiced in the art by those skilled in the art.
Claims (5)
1. A pipeline cleaning process is used for filtering a circulating pipeline and a filter element for preparing olopatadine hydrochloride eye drops and is characterized in that the cleaning process comprises the following steps: circularly flushing the pipeline and the filter element by using benzalkonium chloride solution with the mass fraction of 0.002-0.003 percent, discarding the waste liquid, wherein the flushing time is 35-50min, and the flow speed of the benzalkonium chloride solution during flushing is 0.5-0.7m/s.
2. The pipeline cleaning process according to claim 1, wherein the mass fraction of benzalkonium chloride in the benzalkonium chloride solution is 0.003%, the washing time is 40min, and the flow rate of the benzalkonium chloride solution during washing is 0.55m/s.
3. A preparation method of olopatadine hydrochloride eye drops is characterized by comprising the following steps:
s1: pre-saturating the pipe and filter element by flushing the pipe and filter element according to the pipe cleaning process of any one of claims 1-2;
s2: weighing the following components in parts by weight: 0.5-0.8 part of olopatadine hydrochloride, 0.9-1.3 parts of buffering agent, 0.8-1.3 parts of osmotic pressure regulator, 0.04-0.07 part of bacteriostatic agent, a proper amount of pH regulator and 120-130 parts of water for injection.
S3: adding 50% of the prescription amount of injection water into a mixing tank, cooling to 45 +/-5 ℃ for later use, adding a weighed buffering agent and an osmotic pressure regulator into the mixing tank, pouring a weighed bacteriostatic agent into a stainless steel barrel, adding a proper amount of injection water for dissolving, then pouring the bacteriostatic agent into the mixing tank, stirring and dispersing for 40-60min, and adding the injection water to 80% of the prescription amount;
s4: adjusting pH of the solution to 6.5 + -0.2 with pH regulator, adding the rest injectable water to desired volume, stirring for 10-15min, and mixing;
s5: filtering the solution with constant volume by sequentially passing through polyethersulfone filter membranes with the aperture of 0.45 mu m and the aperture of 0.22 mu m;
s6: the mixture is filled in a low-density polyethylene medicinal eye drop bottle, and the concentration is 5 mg/bottle.
4. The method for preparing olopatadine hydrochloride eye drops according to claim 3, wherein the buffer is disodium hydrogen phosphate, the osmotic pressure regulator is sodium chloride, the bacteriostatic agent is benzalkonium chloride, the pH regulator is hydrochloric acid, and the concentration of the hydrochloric acid is 1mol/L.
5. The method for preparing olopatadine hydrochloride eye drops according to claim 3, wherein the content of olopatadine hydrochloride in 100mL of eye drops is 0.08-0.09g.
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|---|---|---|---|
| CN202211176254.XA CN115569935B (en) | 2022-09-26 | 2022-09-26 | Pipeline cleaning process and preparation method of olopatadine hydrochloride eye drops based on pipeline cleaning process |
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| CN202211176254.XA CN115569935B (en) | 2022-09-26 | 2022-09-26 | Pipeline cleaning process and preparation method of olopatadine hydrochloride eye drops based on pipeline cleaning process |
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105441225A (en) * | 2015-12-18 | 2016-03-30 | 杭州毕肯莱博生物科技有限公司 | Biological instrument pipeline cleaning liquid and preparation method thereof |
| CN105638750A (en) * | 2016-02-25 | 2016-06-08 | 史春艳 | Flushing fluid for sterilizing and disinfecting medical instruments and preparation method |
| JP6153148B1 (en) * | 2017-01-31 | 2017-06-28 | 岩井ファルマテック株式会社 | Process liquid treatment system |
| CN111700860A (en) * | 2020-07-09 | 2020-09-25 | 浙江尖峰药业有限公司 | Olopatadine hydrochloride eye drops and preparation method thereof |
| CN112691429A (en) * | 2020-12-24 | 2021-04-23 | 苏州工业园区天龙制药有限公司 | Multistage filter equipment is used in preparation of olopatadine hydrochloride eye drops |
-
2022
- 2022-09-26 CN CN202211176254.XA patent/CN115569935B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105441225A (en) * | 2015-12-18 | 2016-03-30 | 杭州毕肯莱博生物科技有限公司 | Biological instrument pipeline cleaning liquid and preparation method thereof |
| CN105638750A (en) * | 2016-02-25 | 2016-06-08 | 史春艳 | Flushing fluid for sterilizing and disinfecting medical instruments and preparation method |
| JP6153148B1 (en) * | 2017-01-31 | 2017-06-28 | 岩井ファルマテック株式会社 | Process liquid treatment system |
| CN111700860A (en) * | 2020-07-09 | 2020-09-25 | 浙江尖峰药业有限公司 | Olopatadine hydrochloride eye drops and preparation method thereof |
| CN112691429A (en) * | 2020-12-24 | 2021-04-23 | 苏州工业园区天龙制药有限公司 | Multistage filter equipment is used in preparation of olopatadine hydrochloride eye drops |
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| CN115569935B (en) | 2024-10-11 |
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