CN114788809B - Loratadine liquid preparation - Google Patents

Loratadine liquid preparation Download PDF

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Publication number
CN114788809B
CN114788809B CN202210085001.5A CN202210085001A CN114788809B CN 114788809 B CN114788809 B CN 114788809B CN 202210085001 A CN202210085001 A CN 202210085001A CN 114788809 B CN114788809 B CN 114788809B
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loratadine
weight
parts
liquid
preparation
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CN114788809A (en
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孙先法
张炜峰
张敏
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Jiangsu Guangcheng Pharmaceutical Co ltd
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Jiangsu Guangcheng Pharmaceutical Co ltd
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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
    • A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
    • A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
    • 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
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/12—Carboxylic acids; Salts or anhydrides thereof
    • 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
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • 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
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/38—Cellulose; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/02—Nasal agents, e.g. decongestants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents

Abstract

The invention relates to a loratadine liquid preparation. Specifically, the invention provides a loratadine liquid preparation which comprises loratadine, a flavoring agent, a stabilizing agent and a solvent. The liquid loratadine hydrobromide preparation provided by the invention has excellent stability.

Description

Loratadine liquid preparation
Technical Field
The invention relates to the field of pharmaceutical preparations, in particular to a loratadine liquid preparation.
Background
Loratadine is an antihistamine drug commonly used for treating allergic symptoms, and is used for treating allergic rhinitis, acute or chronic urticaria, allergic conjunctivitis, pollinosis and other allergic skin diseases, and has a CAS number of 7979794-75-5 and a structural formula as follows:
Figure BDA0003487295380000011
the existing loratadine preparation mainly comprises a solid preparation such as loratadine tablets and a liquid preparation such as loratadine syrup, wherein the solid preparation such as the loratadine tablets relate to the dissolution of the medicine, and have slow effect, poor content uniformity and inconvenient administration. For liquid preparations such as loratadine syrup, the loratadine can quickly exert the treatment effect because the problem of drug dissolution is not involved, and the liquid preparations are convenient to take and have strong patient compliance, so the loratadine liquid preparations such as syrup can effectively exert the treatment effect of loratadine and improve the patient compliance.
However, the existing liquid loratadine formulations have many disadvantages, for example, the stability of loratadine syrup is easily affected by various factors, especially, such as light and heat, resulting in decreased contents and increased impurities, and poor stability, and in order to improve the stability, the existing liquid loratadine formulations are filled in brown bottles and added with a large amount of preservatives and stored under light-shielding and high-temperature-avoiding conditions, which not only increases the production, packaging, transportation and storage costs of the liquid formulations such as syrup, but also makes it difficult for patients to easily and rapidly and effectively observe the properties of the loratadine liquid formulations such as syrup in the brown bottles before purchasing or using the liquid formulations such as syrup, such as clarity, presence or absence of precipitated particles, mold, rancidity, discoloration, foreign substances, gas generation and other deterioration phenomena, thus easily causing a problem of medication safety.
Therefore, there is a need in the art to develop a liquid formulation of loratadine having excellent stability.
Disclosure of Invention
The object of the present invention is to provide a liquid loratadine formulation having excellent stability.
In a first aspect of the invention, a loratadine liquid preparation is provided, which comprises loratadine, a flavoring agent, a stabilizing agent and a solvent.
Preferably, the liquid formulation is an oral formulation.
Preferably, the liquid formulation is an oral solution.
Preferably, the loratadine is present in an amount of 0.02-0.5wt%, more preferably 0.05-0.2wt%, more preferably 0.05-0.15wt%, more preferably 0.08-0.12wt%, most preferably 0.1wt%, based on the weight of the liquid loratadine formulation.
Preferably, the loratadine is present in an amount of 0.2 to 5 parts by weight, more preferably 0.5 to 2 parts by weight, still more preferably 0.5 to 1.5 parts by weight, still more preferably 0.8 to 1.2 parts by weight, most preferably 1 part by weight.
Preferably, the flavoring agent is sucralose.
Preferably, the sucralose is contained in an amount of 0.02 to 0.5wt%, more preferably 0.05 to 0.2wt%, more preferably 0.05 to 0.15wt%, more preferably 0.06 to 0.1wt%, most preferably 0.08wt%, based on the weight of the loratadine liquid preparation.
Preferably, the sucralose is present in an amount of 0.2 to 5 parts by weight, more preferably 0.5 to 2 parts by weight, more preferably 0.5 to 1.5 parts by weight, more preferably 0.6 to 1 part by weight, and most preferably 0.8 part by weight.
Preferably, the stabilizer is tartaric acid, sorbitol, sodium chloride and hydroxypropyl methylcellulose.
Preferably, the tartaric acid is present in an amount of 0.1-2 wt.%, more preferably 0.1-1 wt.%, more preferably 0.2-0.6 wt.%, more preferably 0.3-0.5 wt.%, most preferably 0.4 wt.%, based on the weight of the liquid loratadine formulation.
Preferably, the tartaric acid is 1-20 parts by weight, more preferably 1-10 parts by weight, more preferably 2-6 parts by weight, more preferably 3-5 parts by weight, most preferably 4 parts by weight.
Preferably, the sorbitol is present in an amount of 1 to 5wt%, more preferably 2 to 4wt%, more preferably 2.5 to 3.5wt%, more preferably 2.8 to 3.2wt%, most preferably 3wt%, based on the weight of the liquid loratadine formulation.
Preferably, the sorbitol is 10 to 50 parts by weight, more preferably 20 to 40 parts by weight, more preferably 25 to 35 parts by weight, more preferably 28 to 32 parts by weight, most preferably 30 parts by weight.
Preferably, the sodium chloride is present in an amount of 0.2 to 2.0wt%, more preferably 0.5 to 1.5wt%, more preferably 0.6 to 1.0wt%, more preferably 0.7 to 0.9wt%, most preferably 0.8wt%, based on the weight of the loratadine liquid formulation.
Preferably, the sodium chloride is present in an amount of 2 to 20 parts by weight, more preferably 5 to 15 parts by weight, more preferably 6 to 10 parts by weight, more preferably 7 to 9 parts by weight, most preferably 8 parts by weight.
Preferably, the hydroxypropyl methylcellulose is present in an amount of 0.2 to 2 wt.%, more preferably 0.2 to 1.0 wt.%, more preferably 0.4 to 0.8 wt.%, more preferably 0.5 to 0.7 wt.%, most preferably 0.6 wt.%, based on the weight of the liquid loratadine formulation.
Preferably, the hydroxypropyl methylcellulose is 2-20 parts by weight, more preferably 2-10 parts by weight, more preferably 4-8 parts by weight, more preferably 5-7 parts by weight, and most preferably 6 parts by weight.
Preferably, the solvent comprises glycerol, ethanol and water.
Preferably, the glycerol is present in an amount of 2 to 6wt%, more preferably 3 to 5wt%, more preferably 3.5 to 4.5wt%, more preferably 3.8 to 4.2wt%, most preferably 4.0wt%, based on the weight of the liquid loratadine formulation.
Preferably, the glycerol is 20 to 60 parts by weight, more preferably 30 to 50 parts by weight, more preferably 35 to 45 parts by weight, more preferably 38 to 42 parts by weight, most preferably 40 parts by weight.
Preferably, the ethanol is present in an amount of 0.5 to 4wt%, more preferably 1 to 3wt%, more preferably 1.5 to 2.5wt%, more preferably 1.8 to 2.2wt%, most preferably 2.0wt%, based on the weight of the loratadine liquid formulation.
Preferably, the ethanol is 5 to 40 parts by weight, more preferably 10 to 30 parts by weight, more preferably 15 to 25 parts by weight, more preferably 18 to 22 parts by weight, most preferably 20 parts by weight.
Preferably, the water is purified water or water for injection.
Preferably, the amount of water is 900 to 1100 parts by weight, preferably 920 to 1050 parts by weight, more preferably 900 to 1000 parts by weight, still more preferably 920 to 970 parts by weight, most preferably 930 to 960 parts by weight.
Preferably, the liquid loratadine preparation comprises loratadine, sucralose, glycerin, ethanol, tartaric acid, sorbitol, sodium chloride, hydroxypropylmethylcellulose and water.
Preferably, the liquid loratadine formulation comprises:
Figure BDA0003487295380000031
Figure BDA0003487295380000041
preferably, the liquid loratadine formulation comprises:
components Dosage of
Loratadine 0.8 to 1.2 parts by weight of
Sucralose 0.7 to 0.9 portion
Glycerol 38 to 42 parts by weight of
Ethanol 18 to 22 portions of
Tartaric acid 3.8 to 4.2 portions of
Sorbitol 28-32 parts by weight
Sodium chloride 7 to 9 parts by weight of
Hydroxypropyl methylcellulose 5-7 parts by weight; and
water (I) 920-960 parts by weight.
Preferably, the liquid loratadine formulation comprises:
components Dosage of
Loratadine 1.0 part by weight
Sucralose 0.8 part by weight
Glycerol 40 parts by weight of
Ethanol 20 parts by weight of
Tartaric acid 4 parts by weight of
Sorbitol 30 parts by weight of
Sodium chloride 8 parts by weight
Hydroxypropyl methylcellulose 6 parts by weight; and
water (W) 930-960 parts by weight.
Preferably, the liquid loratadine formulation comprises:
components Dosage of
Loratadine 1.0g
Sucralose 0.8g
Glycerol 40g
Ethanol 20g
Tartaric acid 4g
Sorbitol 30g
Sodium chloride 8g
Hydroxypropyl methylcellulose 6g
Water (W) To 1000ml.
Preferably, the unit of parts by weight is g.
Preferably, the loratadine liquid preparation is subpackaged in transparent containers.
Preferably, the transparent container comprises a transparent plastic container or a transparent glass container.
Preferably, the transparent plastic container comprises a transparent PET bottle.
In a second aspect of the present invention, there is provided a process for preparing a liquid loratadine formulation according to the first aspect of the present invention, said process comprising the steps of:
and mixing the loratadine, the flavoring agent, the stabilizing agent and the solvent to obtain the loratadine liquid preparation.
Preferably, the liquid loratadine preparation is prepared by the following method:
mixing loratadine, sucralose, glycerol, ethanol, tartaric acid, sorbitol, sodium chloride, hydroxypropyl methylcellulose and water to obtain the liquid loratadine preparation.
Preferably, after mixing, filtering through a microporous membrane to obtain the loratadine liquid preparation.
Preferably, the method comprises the steps of:
mixing glycerol and ethanol, adding loratadine, stirring and mixing at 40-50 ℃, adding 75-85% of water according to the formula amount, stirring and mixing at 40-50 ℃, adding sucralose, tartaric acid, sorbitol, sodium chloride and hydroxypropyl methylcellulose, stirring and mixing at 40-50 ℃, adding water to a fixed volume to obtain a loratadine liquid preparation.
Preferably, water is added to the prepared volume, and the liquid loratadine preparation is obtained after filtration.
Preferably, the filtration is microfiltration.
Preferably, the size of the filtration pores of the microporous filtration membrane is 0.10 to 1.0 μm, preferably 0.22 μm, 0.45 μm or 0.80 μm.
In a third aspect of the invention, there is provided a kit comprising a transparent container and a liquid formulation of loratadine according to the first aspect of the invention.
Preferably, said liquid formulation of loratadine according to the first aspect of the invention is dispensed into said transparent container.
Preferably, the transparent container contains the liquid formulation of loratadine according to the first aspect of the invention.
Preferably, the transparent container comprises a transparent plastic container or a transparent glass container.
Preferably, the transparent plastic container comprises a transparent PET bottle.
In a fourth aspect of the invention, there is provided the use of a liquid formulation of loratadine according to the first aspect of the invention for the manufacture of a medicament for the treatment of allergic symptoms.
Preferably, the allergic symptoms include symptoms associated with allergic rhinitis (e.g., sneezing, nasal discharge, nasal itching, nasal obstruction, and ocular itching and burning) and/or symptoms of allergic skin diseases (e.g., urticaria, pruritic skin diseases).
It is to be understood that within the scope of the present invention, the above-described features of the present invention and those specifically described below (e.g., in the examples) may be combined with each other to form new or preferred embodiments.
Detailed Description
The invention provides a loratadine liquid preparation which comprises loratadine, a flavoring agent, a stabilizing agent and a solvent. The loratadine liquid preparation provided by the invention has excellent thermal stability and light stability, so that the loratadine liquid preparation is convenient to store and transport. In addition, the loratadine liquid preparation does not contain sucrose and glucose which cause rapid rise of blood sugar, and is suitable for patients with hyperglycemia and diabetes to take, so that the people taking the loratadine liquid preparation are expanded.
Term(s) for
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.
As used herein, the terms "comprises," "comprising," "includes," "including," and "including" are used interchangeably and include not only closed-form definitions, but also semi-closed and open-form definitions. In other words, the term includes "consisting of 8230; \8230; composition;" consisting essentially of 8230; \8230; composition 8230).
In the liquid loratadine formulations of the present invention, the weight content (wt%) or concentration (e.g., mg/mL) of each component is based on the weight or volume of the liquid loratadine formulation.
The term "glycerol" as used herein refers to 1,2, 3-propanetriol.
As used herein, the terms "hydroxypropylmethylcellulose", "hydroxypropylmethylcellulose" and "hypromellose" are used interchangeably with CAS number 9004-65-3.
As used herein, the term "PET" refers to polyester, and "pharmaceutical polyester bottles" and "pharmaceutical PET bottles" are used slowly.
As used herein, the term "part by weight" can be any fixed weight expressed in milligrams, grams, or kilograms (e.g., 1mg, 1g, or 1kg, etc.). For example, a composition consisting of 1 part by weight of component a and 9 parts by weight of component b may be a composition consisting of 1g of component a +9 g of component b, or 10 g of component a +90 g of component b. In the liquid loratadine formulation, the percentage content of a component = (the weight part of the component/the sum of all the weight parts of the component) × 100%, and thus, in a composition consisting of 1 weight part of component a and 9 weight parts of component b, the content of component a is 10% and the content of component b is 90%.
Loratadine liquid preparation and preparation method thereof
The invention provides a loratadine liquid preparation which comprises loratadine, a flavoring agent, a stabilizing agent and a solvent.
The dosage form of the loratadine liquid preparation is preferably oral solution.
In particular, the liquid loratadine formulations of the present invention are as described above in the first aspect of the invention.
The loratadine liquid preparation can be subpackaged in transparent containers. The transparent container comprises a transparent plastic (such as PET) container or a transparent glass container.
Typically, the liquid loratadine formulation comprises:
components Dosage of
Loratadine 0.5 to 1.5 parts by weight of
Sucralose 0.4 to 1.2 parts by weight of
Glycerol 30-50 parts by weight
Ethanol 15-25 parts by weight
Tartaric acid 2 to 6 portions of
Sorbitol 25-35 parts by weight
Sodium chloride 6 to 10 parts by weight of
Hydroxypropyl methylcellulose 4-8 parts by weight; and
water (W) 920-960 parts by weight.
Typically, the liquid loratadine formulation comprises:
components Dosage of
Loratadine 0.8 to 1.2 parts by weight of
Sucralose 0.7 to 0.9 part by weight
Glycerol 38 to 42 parts by weight of
Ethanol 18 to 22 portions of
Tartaric acid 3.8 to 4.2 parts by weight of
Sorbitol 28-32 parts by weight
Sodium chloride 7 to 9 parts by weight of
Hydroxypropyl methylcellulose 5-7 parts by weight; and
water (W) 920-960 parts by weight.
Typically, the liquid loratadine formulation comprises:
components Dosage of
Loratadine 1.0 part by weight
Sucralose 0.8 part by weight
Glycerol 40 parts by weight of
Ethanol 20 parts by weight of
Tartaric acid 4 parts by weight of
Sorbitol 30 parts by weight of
Sodium chloride 8 parts by weight
Hydroxypropyl methylcellulose 6 parts by weight; and
water (W) 930-960 parts by weight.
Typically, the liquid loratadine formulation comprises:
components Amount of the composition
Loratadine 1.0g
Sucralose 0.8g
Glycerol 40g
Ethanol 20g
Tartaric acid 4g
Sorbitol 30g
Sodium chloride 8g
Hydroxypropyl methyl celluloseVitamin (I) 6g
Water (I) To 1000ml.
The invention also provides a preparation method of the loratadine liquid preparation, which comprises the following steps:
and mixing the loratadine, the flavoring agent, the stabilizing agent and the solvent to obtain the loratadine liquid preparation.
In a preferred embodiment of the invention, the loratadine liquid preparation is prepared by the following method:
mixing loratadine, sucralose, glycerol, ethanol, tartaric acid, sorbitol, sodium chloride, hydroxypropyl methylcellulose and water to obtain the liquid loratadine preparation.
Preferably, after mixing, filtering through a microporous membrane to obtain the loratadine liquid preparation.
Preferably, the size of the filtration pores of the microporous filtration membrane is 0.10 to 1.0 μm, preferably 0.22 μm, 0.45 μm or 0.80 μm.
Typically, the liquid loratadine formulation is prepared by the following method:
mixing glycerol and ethanol, adding loratadine, stirring and mixing at 40-50 ℃, adding 75-85% of water according to the formula amount, stirring and mixing at 40-50 ℃, adding sucralose, tartaric acid, sorbitol, sodium chloride and hydroxypropyl methylcellulose, stirring and mixing at 40-50 ℃, adding water to a constant volume to obtain a loratadine liquid preparation.
The main excellent technical effects of the invention comprise:
1. the invention develops a loratadine liquid preparation which has light stability and can be simply subpackaged in a transparent container for storage and transportation without being subpackaged in a brown container for storage and transportation.
2. The loratadine liquid preparation developed by the invention has excellent thermal stability and is convenient to store and transport, so that the cost of storage, transportation and the like is reduced, and the economic benefit is improved.
The invention will be further illustrated with reference to the following specific examples. It should be understood that these examples are for illustrative purposes only and are not intended to limit the scope of the present invention. The experimental methods in the following examples, which are not specified under specific conditions, are generally performed under conventional conditions.
EXAMPLE 1 oral solution of loratadine
The formula of the loratadine oral solution of this example 1 is shown in table 1:
TABLE 1 composition of the prescription of loratadine oral solution (loratadine 1.0 mg/ml)
Components Dosage of
Loratadine 1.0g
Sucralose 0.8g
Glycerol 40g
Ethanol 20g
Tartaric acid 4g
Sorbitol 30g
Sodium chloride 8g
Hydroxypropyl methylcellulose 6g
Purified water To 1000ml
The preparation method of the loratadine oral solution comprises the following steps:
mixing glycerol and ethanol, adding loratadine, stirring and mixing at 45 ℃, adding 80% of the formula amount of purified water, stirring and mixing at 45 ℃, adding sucralose, tartaric acid, sorbitol, sodium chloride and hydroxypropyl methyl cellulose, stirring and mixing at 45 ℃, adding the rest formula amount of purified water to a dosage volume, filtering through a 0.22 mu m microporous filter membrane to obtain a loratadine oral solution, and subpackaging in transparent PET bottles.
Comparative example 1 oral loratadine solution
The prescription of the loratadine oral solution of this comparative example 1 is shown in table 2:
TABLE 2 composition of loratadine oral solution (loratadine 1.0 mg/ml)
Components Amount of the composition
Loratadine 1.0g
Sucralose 0.8g
Glycerol 40g
Ethanol 20g
Tartaric acid 4g
Sorbitol 10g
Sodium chloride 8g
Hydroxypropyl methylcellulose 6g
Purified water To 1000ml
The preparation method of the loratadine oral solution comprises the following steps:
mixing glycerol and ethanol, adding loratadine, stirring and mixing at 45 ℃, adding 80% of the formula amount of purified water, stirring and mixing at 45 ℃, adding sucralose, tartaric acid, sorbitol, sodium chloride and hydroxypropyl methyl cellulose, stirring and mixing at 45 ℃, adding the rest formula amount of purified water to a dosage volume, filtering through a 0.22 mu m microporous filter membrane to obtain a loratadine oral solution, and subpackaging in transparent PET bottles.
Comparative example 2 oral loratadine solution
The formula of the loratadine oral solution of comparative example 2 is shown in table 3:
TABLE 3 prescription composition of loratadine oral solution (loratadine 1.0 mg/ml)
Figure BDA0003487295380000101
Figure BDA0003487295380000111
The preparation method of the loratadine oral solution comprises the following steps:
mixing glycerol and ethanol, adding loratadine, stirring and mixing at 45 ℃, adding 80% of purified water according to the prescription amount, stirring and mixing at 45 ℃, adding sucralose, tartaric acid, sorbitol, sodium chloride and hydroxypropyl methylcellulose, stirring and mixing at 45 ℃, adding the rest purified water according to the prescription amount to a dosage volume, filtering through a 0.22 mu m microporous filter membrane to obtain a loratadine oral solution, and subpackaging in transparent PET bottles.
Comparative example 3 oral loratadine solution
The prescription of the loratadine oral solution of this comparative example 3 is shown in table 4:
TABLE 4 composition of the prescription of loratadine oral solution (loratadine 1.0 mg/ml)
Components Dosage of
Loratadine 1.0g
Sucralose 0.8g
Glycerol 40g
Ethanol 20g
Tartaric acid 4g
Sodium chloride 8g
Purified water To 1000ml
The preparation method of the loratadine oral solution comprises the following steps:
mixing glycerol and ethanol, adding loratadine, stirring and mixing at 45 ℃, adding 80% of purified water according to the prescription amount, stirring and mixing at 45 ℃, adding sucralose, tartaric acid and sodium chloride, stirring and mixing at 45 ℃, adding the rest purified water according to the prescription amount to a dosage volume, filtering through a 0.22 mu m microporous filter membrane to obtain a loratadine oral solution, and subpackaging in transparent PET bottles.
Comparative example 4 oral solution of loratadine
The prescription of the loratadine oral solution of this comparative example 4 is shown in table 5:
TABLE 5 composition of the prescription of loratadine oral solution (loratadine 1.0 mg/ml)
Figure BDA0003487295380000112
Figure BDA0003487295380000121
The preparation method of the loratadine oral solution comprises the following steps:
mixing glycerol and ethanol, adding loratadine, stirring and mixing at 45 ℃, adding 80% of purified water according to the prescription amount, stirring and mixing at 45 ℃, adding sucralose, tartaric acid, sodium chloride and hydroxypropyl methylcellulose, stirring and mixing at 45 ℃, adding the rest purified water according to the prescription amount to a dosage volume, filtering through a 0.22 mu m microporous membrane to obtain a loratadine oral solution, and subpackaging in transparent PET bottles.
Comparative example 5 oral solution of loratadine
The prescription of the loratadine oral solution of this comparative example 5 is shown in table 6:
TABLE 6 composition of loratadine oral solution (loratadine 1.0mg/ml in specification)
Components Dosage of
Loratadine 1.0g
Sucralose 0.8g
Glycerol 40g
Ethanol 20g
Tartaric acid 4g
Sorbitol 30g
Sodium chloride 8g
Purified water To 1000ml
The preparation method of the loratadine oral solution comprises the following steps:
mixing glycerol and ethanol, adding loratadine, stirring and mixing at 45 ℃, adding 80% of purified water according to the prescription amount, stirring and mixing at 45 ℃, adding sucralose, tartaric acid, sorbitol and sodium chloride, stirring and mixing at 45 ℃, adding the rest purified water according to the prescription amount to a dosage volume, filtering by a 0.22 mu m microporous membrane to obtain a loratadine oral solution, and subpackaging in transparent PET bottles.
Stability survey
1. Stability study of illumination factors
Referring to the guidelines of the stability test of the Chinese pharmacopoeia preparation, the stability of the loratadine oral solutions prepared in example 1 and comparative examples 1-5, which were distributed in transparent PET bottles, after preparation (0 day), 10 days and 30 days was examined by single factor observation under light (4500lx, 25 ℃), and the loratadine content (%) and the impurity content (%) were measured by HPLC (high performance liquid chromatography), wherein the loratadine content (%) was controlled to 90-100%, the single impurity content was controlled to 0.5% or less, and the total impurity content was controlled to 1.0% or less.
The results of examination of loratadine oral solutions prepared in example 1 and comparative examples 1-5 in clear PET bottles under light (4500 lx,25 ℃) are shown in table 7:
table 7 light factor stability study of loratadine oral solutions prepared in example 1 and comparative examples 1-5
Figure BDA0003487295380000131
As can be seen from table 7, the loratadine oral solution prepared in example 1 has excellent light stability, and can be stored and transported simply by being dispensed in a transparent container, without being dispensed in a brown container to be stored and transported away from light.
2. Accelerated stability review
Referring to the guidelines of the stability test of the Chinese pharmacopoeia preparation, the stability of the loratadine oral solution (packaged in a transparent PET bottle) prepared in example 1 after preparation (0 day), 1, 3 and 6 months is accelerated by performing an accelerated stability test under the conditions that the temperature is 40 +/-2 ℃ and the relative humidity is RH75 +/-5%, and the content (%) of loratadine and the content (%) of impurities are determined by HPLC (high performance liquid chromatography), wherein the content (%) of loratadine is controlled to be 90-100%, the content of single impurities is controlled to be less than or equal to 0.5%, and the content of total impurities is controlled to be less than or equal to 1.0%.
Accelerated stability studies of the loratadine oral solutions prepared in example 1 are shown in table 8:
TABLE 8 accelerated stability (40. + -. 2 ℃ C., RH 75. + -. 5%) of loratadine oral solutions prepared in example 1
Figure BDA0003487295380000141
As can be seen from table 8, the loratadine oral solution prepared in example 1 has excellent accelerated stability, facilitating storage and transportation.
While the invention has been described with respect to one embodiment, it will be understood by those skilled in the art that various changes in form and detail may be made therein without departing from the spirit and scope of the invention.

Claims (5)

1. The liquid loratadine preparation is characterized by comprising the following components in parts by weight:
Figure FDA0004085298330000011
2. the liquid loratadine formulation of claim 1 wherein said liquid loratadine formulation is comprised of:
Figure FDA0004085298330000012
3. the liquid loratadine formulation of claim 1 wherein said liquid loratadine formulation is comprised of:
Figure FDA0004085298330000013
4. a kit comprising a transparent container and a liquid loratadine formulation of claim 1;
the liquid loratadine preparation is separately packaged in the transparent container.
5. Use of the liquid loratadine formulation of claim 1 for the preparation of a medicament for treating allergic symptoms.
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