What Is Aqueous Nasal Spray?
Spray refers to the filling of raw materials or suitable excipients in a special device. When used, the contents are released as a mist by means of the pressure of a manual pump, high-pressure gas, ultrasonic vibration or other methods for inhalation in the lungs or Preparations sprayed directly to the mucosa of the cavity and the skin. Different from aerosols, the power of aerosols to spray drugs is propellants, such as chlorochloroalkanes (which are mostly not used now), hydrofluoroalkanes, dimethyl ether, etc.
Spray refers to the filling of raw materials or suitable excipients in a special device. When used, the contents are released as a mist by means of the pressure of a manual pump, high-pressure gas, ultrasonic vibration or other methods for inhalation in the lungs or Preparations sprayed directly to the mucosa of the cavity and the skin. Different from aerosols, the power of aerosols to spray drugs is propellants, such as chlorochloroalkanes (which are mostly not used now), hydrofluoroalkanes, dimethyl ether, etc.
- Chinese name
- Spray
- Foreign name
- sprays
- Also known as
- Pneumatic preparation
- Particle size
- 10m or less
Aerosol spray definition
Spray refers to the filling of raw materials or suitable excipients in a special device. When used, the contents are released as a mist by means of the pressure of a manual pump, high-pressure gas, ultrasonic vibration or other methods for inhalation in the lungs or Preparations sprayed directly to the mucosa of the cavity and the skin. Different from aerosols, the power of aerosols to spray drugs is propellants, such as chlorochloroalkanes (which are mostly not used now), hydrofluoroalkanes, dimethyl ether, etc. [1]
Production and storage of sprays
Sprays should be prepared in the environment required by the relevant species, such as certain cleanliness, sterilization conditions and low temperature environments.
Additives such as solvents, co-solvents, antioxidants, bacteriostatic agents, and surfactants can be added as needed. When determining the formulation prescription, the bacteriostatic effect of the bacteriostatic agent should conform to the bacteriostatic effect inspection method (Chinese Pharmacopoeia General Rule 1121 )Provisions. Additives should be non-irritating to the skin or mucous membranes.
All components in the spray device should be made of non-toxic, non-irritating, stable properties, and do not work with drugs.
The solution of the spray solution should be clarified; the droplets of the emulsion spray should be uniformly dispersed in the liquid medium; the suspension spray should be thoroughly mixed and ground with the fine powder of the drug and the additive to make it stable Suspension. The size of the droplets (particles) for inhalation after being atomized by the atomizer should be controlled below 10 m, and most of them should be below 5 m.
Unless otherwise specified, sprays should be sealed and stored away from light.
Inhalation sprays and metered-dose sprays for nebulizers should be sterile. [1]
Spray classification
Sprays are divided into solution type, emulsion type or suspension type according to the content composition. According to the route of administration, it can be divided into inhalation spray, nasal spray and non-inhalation spray for skin and mucous membrane. Sprays can be divided into quantitative sprays and non-quantitative sprays according to the dosage. Among them, the inhalation spray for atomizer refers to the solution, suspension or emulsion of aerosol for inhalation generated by a continuous nebulizer; the inhalation spray for quantitative inhalation refers to the generation of aerosol for inhalation by a quantitative nebulizer Solution, suspension or emulsion.
At present, there are two types of sprays that are widely used in clinics: oral sprays and nasal sprays .
Oral spray
Oral mucosal administration has the advantages of rapid drug absorption, low enzyme activity, avoidance of the first pass effect of the liver, and convenient administration. It has become one of the non-injection routes for the development of peptide, protein and vaccine drugs. Among the many oral mucosa dosage forms, the oral spray preparation process is simple, and the drug is quickly absorbed by contact with the mucous membrane. It is especially suitable for drugs that require rapid onset of action, and is suitable for patients and children who have difficulty swallowing. It can deliver the drug to the oral mucosa or oropharynx and other parts to play a local role, and the drug can also be absorbed through the part of the mucosa to play a systemic role.
At present, the application of oral sprays is mainly in the following aspects: For the treatment of local diseases, oral sprays have been widely used to treat various oral and throat diseases, such as oral ulcers, sore throats, mucosal diseases, and dry mouth diseases. Bendamin hydrochloride oral spray (trade name: Difflam spray) from Meda Pharmaceuticals can relieve pharyngitis, tonsillitis, oral ulcers, and pain after oral surgery. In the treatment of cardiovascular diseases, oral sprays can play a fast-acting role in the treatment of cardiovascular diseases. In 2005, the FDA approved NovaDel Pharmaceuticals' nitroglycerin sublingual spray (trade name: NitroMist) for coronary heart disease and angina pectoris. treatment. (3) Analgesic, fentanyl oral spray is used for the treatment of sudden pain, with rapid onset, convenient use, and high patient compliance. Sedative hypnosis. In 2008, the FDA approved NovaDel Pharmaceutical Zolpidem Tartrate Oral Spray (Trade Name: ZolpiMist) for the treatment of insomnia that is difficult to fall asleep. Agents are also under development. Diabetes, Oral-Lyn, an insulin oral spray developed by Generex Biotechnology Company of Canada, was launched in India, Ecuador and Lebanon from 2007 to 2009. It was launched in Canada in 2010 and can be used to treat type 1 and type 2 diabetes. .
From the above, oral sprays can be used to treat a variety of local and systemic diseases. However, due to the small total area of the oral mucosa, the residence time of the drug in the oral mucosa after oral spray administration is usually short. Currently, oral sprays are used. The number of preparations for systemic administration is very limited, especially oral sprays of macromolecules and vaccines are still in their infancy. [2]
Nasal spray
Nasal sprays are one of the subtypes of sprays. The human nasal airway is composed of a nasal septum, a turbinate, and soft mucosal soft tissue that is open in the sinuses and is covered with a highly vascularized mucosal tissue. The administration of nasal sprays is similar to inhaled aerosols. However, the droplets sprayed by the spray are relatively large, staying mainly in the nasal cavity without entering the trachea and lungs, and acting through the absorption of the nasal mucosa. Therefore, the action site is different from the aerosol. In clinical treatment, nasal spray is a new non-injection method, which is often used to treat clinical diseases such as pain, allergic rhinitis, diabetes, and sinus infection, as shown in Table 1. Sprays can exert powerful anti-inflammatory and anti-edema effects at various stages of inflammation, and can promote the repair of damaged ciliated epithelium. It is currently the first-line drug for treating nasal inflammatory diseases and occupies a major share in clinical practice. At the same time, due to the rapid development of the biopharmaceutical industry, for some oral bioavailable biotech drugs, such as peptides, proteins, and nucleic acids, nasal sprays may become important for local or systemic administration of these drugs. way. [3-5]
Table 1 Representative nasal sprays currently marketed in China
Drug name | Product name | Drug effect | |
Fluticasone propionate nasal spray | Fu Shuliang | Treatment of allergic rhinitis |
Ketorolac tromethamine nasal spray | Sprix | Short-term treatment of moderate to severe pain (5 days) |
Salmon calcitonin nasal spray | Secret interest | Treatment of osteoporosis and hypercalcemia |
Nasal spray | Huanbao | For Xin Wen San cold, Tongli nose |
Azelastine Hydrochloride Nasal Spray | Isaipin | Treatment of seasonal or perennial allergic rhinitis (hay fever) |
Triamcinolone nasal spray | Bino | Prevention and treatment of perennial and seasonal allergic rhinitis in adults and children over 6 years of age |
Butorphin tartrate nasal spray | Noyan | Relieves a variety of cancerous pain and post-operative pain |
Oxytocin nasal spray | Ossetian | Strengthen uterine contraction, promote the contraction of smooth muscle cells around breast acinars, and promote milk production |
Compound Bear Gall Nasal Spray | Must spray | Shufeng Tongqiao, suitable for acute rhinitis, nasal congestion, runny nose |
Spray quality inspection
Unless otherwise specified, sprays shall be inspected accordingly.
Each bottle of multi-dose quantitative sprays should be inspected according to the following methods, and they should meet the requirements.
Inspection method: Take 4 bottles of test product, remove the cap, shake well, and follow the instruction manual. In the fume hood, press the valve to spray continuously into the container with the appropriate amount of absorption liquid (note that the interval between each spray is 5 seconds) And slowly shake) until the spray is exhausted, calculate the number of sprays separately, the total spray number of each bottle must not be less than the total spray number.
Unless otherwise specified, the amount of spray spray shall be checked in accordance with the following methods and shall comply with the regulations.
Inspection method: Take 4 bottles for the test product and follow the instructions of the user. After spraying several times, clean and accurately weigh, and then spray 3 times in succession. Wipe clean after each spray, accurately weigh and calculate each time. Spraying amount, continuous spraying 10 times, clean, accurately weighed, and then measure the spraying amount 3 times according to the above method. After continuing to spray 10 times, measure the spraying amount 4 times according to the above method, and calculate the spraying amount of 10 times per bottle. average value. Unless otherwise specified, they should be 80% to 120% of the indicated spray volume. For sprays that are required to determine the content of the main drug or the uniformity of the delivered dose per spray, the determination of the amount of spray per spray is no longer performed.
Unless otherwise specified, the amount of the main drug in each spray shall be checked in accordance with the following method, and the content of the main drug in each spray shall meet the requirements.
Inspection method: Take 1 bottle of test product, follow the instruction manual, spray 5 times, wash the nozzle with solvent, and fully dry, then spray 10 or 20 times (note that the interval between spraying is 5 seconds and shake slowly) , Collected in a certain amount of absorption solvent, transferred to a suitable measuring bottle and diluted to the mark, shake well, and measure. The result obtained is divided by 10 or 20, which is the average main drug content per spray, and the main drug content per spray should be 80% to 120% of the labeled content. For sprays that are required to determine the uniformity of the delivered dose, the determination of the main drug content per spray is generally no longer performed.
Uniformity of delivered dose Unless otherwise specified, quantitative inhalation sprays, suspension and emulsion quantitative nasal sprays should be checked for uniformity of delivered doses according to inhaled preparations (Chinese Pharmacopoeia General Rule 0111) or nasal preparations (Chinese Pharmacopoeia General rule 106) The method inspection under relevant items shall meet the requirements.
Unless otherwise specified, the dose of fine particles for inhalation sprays for nebulizers should be checked for the dose of fine particles, and the aerodynamic characteristics of fine particles of inhaled preparations (Chinese Pharmacopoeia Appendix 0951) should be checked. The method should be determined in accordance with the law and the dose of fine particles should be calculated in accordance with the regulations.
Delivery rate and total amount of delivery Unless otherwise specified, inhalation sprays for nebulizers should be checked for active substance delivery rate and total amount of delivery, and tested in accordance with the methods of inhalation preparations (Chinese Pharmacopoeia General Rule 0111), which should meet the requirements .
Unless otherwise specified, the single-dose spray should be inspected in accordance with the following method, and it should meet the requirements.
Inspection method: Unless otherwise specified, 20 test samples are taken, and the content and average content of each content are obtained according to the method specified under each item. Compared with the average filling quantity, the loading quantity of each one does not exceed two, and no one exceeds the limit.
Average loading | Limit of loading difference |
30g or less
| ± 10% |
30g and above 0.30g
| ± 7.5% |
For single-dose sprays that are required to check the uniformity of content, the inspection of the difference in loading is generally not performed.
The non-quantitative sprays should be inspected according to the minimum loading inspection method (General Principles of the Chinese Pharmacopoeia 0942), which should meet the requirements.
Unless otherwise specified, inhalation sprays, metered-dose sprays for nebulizers, and aseptic sprays for burns, severe trauma, or clinical necessities must be inspected in accordance with the Aseptic Assay (Chinese Pharmacopoeia General Rule 1101) ,meets the requirments.
Unless otherwise specified, the microbiological limit inspection method (Chinese Pharmacopoeia General Rules 1105 ~ 1107) shall be used for inspection, and shall comply with the regulations.
Among them, inhalation sprays should meet the requirements under inhalation preparations (Chinese Pharmacopoeia General Rule 0111) in addition to the requirements under aerosols; nasal sprays should also meet nasal use in addition to the requirements under aerosols. Preparations (Chinese Pharmacopoeia General Rule 0106) related requirements. [1]
