Pharmaceutical preparations are drugs that are made in accordance with the requirements of a certain dosage form and can be provided to the subject of medication. The purpose is to meet the needs of treating or preventing diseases. The research and development of pharmaceutical preparations can create pharmaceutical preparations that meet the preparation requirements of the innovative drug development stage by using preparation technologies that improve bioavailability based on pre-prescription information. Medicilon can help customers provide pre-pharmaceutical preparation and pharmaceutical preparation research services, and provide reliable data for CMC application materials.
Inhalation preparations are liquid or solid preparations that dissolve or disperse the raw materials in a suitable medium and administer them to the lungs in the form of vapor or aerosol to exert local or systemic effects. They are used to prevent and treat asthma, chronic obstructive pulmonary disease (COPD) and other respiratory diseases The preferred method of administration. Common inhalation preparations include inhalation aerosols, atomized inhalation liquid preparations and inhalation powder mists. This article first introduces the formulation and development of inhalation aerosol pharmaceutical preparations.
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Inhalation aerosol is a preparation in which medicine and propellant are co-encapsulated in a pressure-resistant container with a quantitative valve system, and the content is sprayed out as a mist under the pressure of the propellant during use, which is used for lung inhalation. The basic prescription composition of aerosols includes drugs and propellants. In addition to propellants, co-solvents, surfactants, stabilizers, etc. may be added.
Medicilon is familiar with the development process and has extensive R&D experience of various inhalation formulations, especially in the field of DPI, nebulizer and nasal spray. The R&D are fully integrated with the requirements of domestic and foreign policies, regulations and guidelines.
Propellant is a substance that provides aerosol power, and generally acts as a solvent or diluent for drugs. The prescription composition of aerosols can be divided into:
(1) There are only drugs and propellants in the prescription, and the drugs are dissolved or suspended in the propellant;
(2) The prescription contains drugs, propellants, co-solvents, and co-solvents such as absolute ethanol;
(3) The prescription contains drugs, propellants, co-solvents, and surfactants. The addition of surfactants in the prescription can generally make the drugs better dispersed in the solvent, and can lubricate and improve the performance of the valve system;
(4) In addition to the above composition, other ingredients may be added, such as antioxidants and pH regulators that need to increase drug stability.
Due to differences in the physical and chemical properties and stability of drugs, aerosols are generally developed into two types: solution type and suspension type. Two different types of aerosols need to focus on the properties of different APIs, and they should be fully understood and studied during pre-prescription research and formulation development. For solution-type aerosols, it is necessary to understand the solubility, chemical stability, impurities, etc.; for suspension-type aerosols, it is necessary to study and understand the crystal form and transformation of the raw materials, the particle size distribution of the raw materials, and the density of the drug. Powder particle shape, surface energy, moisture, moisture absorption, etc. Compared with solution-type aerosols, suspension-type aerosols usually require more evaluation and research on the properties of APIs, which is usually more difficult.
The difficulty in the development of aerosols is that there are many factors affecting product quality attributes, especially suspension aerosols. In addition to prescription factors such as the properties of raw materials, prescription composition and dosage, the tank body, especially the valve and actuator, are also very affected. In addition, the domestic production technology and equipment are relatively backward. For some suitable content prescriptions, it is difficult to realize the technology or equipment and industrialization is difficult.
When formulating the formulation, you can design the prescription of the contents according to the specifications of the valve system, drug specifications, and total orders, including the dosage of active ingredients; or select the specifications of the valve system according to the basic drug concentration and drug specifications of the prescription, and On this basis, appropriately adjust the prescription and the dosage of the main drug according to the experimental results, and first ensure that the specifications of each product meet the regulations.
The development of aerosol formulations and the screening of tanks, valves and actuators can be carried out simultaneously. The prescription composition of the medicinal solution can be adjusted according to needs, such as: adding absolute ethanol to meet the feasibility requirements of the process or meeting the dissolution requirements of the drug; adding surfactants to meet the dispersibility requirements of the drug; to meet the stability of the drug Add antioxidants, pH regulators, etc. to meet sexual needs.
When formulating a formulation, it is first necessary to understand the general requirements of inhaled aerosols for the formulation factors, such as the requirements for the particle size of the raw materials of suspension aerosols, and the influence of the moisture of the contents.
Secondly, it is necessary to understand and evaluate various prescription factors (original and excipient attributes, prescription composition and dosage, etc.) and the quality attributes of inhaled aerosols (appearance of the liquid medicine, content of each molybdenum, uniformity of delivered dose, total number of presses, and droplet size Distribution and aerodynamic droplet (particle) distribution (two-stage impact collection and ACI, NGI multi-stage impact collection), impurities, leakage rate, spray pattern, etc.), analyze which prescription factors may affect which quality attributes of aerosols, In order to develop prescriptions more specifically.
For example, the flocculation, sedimentation and uniformity of redispersion of suspended aerosol drugs may be affected by raw material particle size distribution, raw material surface energy, density and particle morphology, and other raw material properties, as well as the formulation and dosage. Such as the influence of the type and proportion of the propellant in the prescription; the influence of the proportion and amount of ethanol and the propellant (such as adding ethanol); the influence of the type and amount of wetting agent (such as adding wetting agent); the influence of moisture content, etc. Wait.
Therefore, when formulating the formulation, it is necessary to fully study the influence of the above-mentioned various prescription factors on the physical stability of the suspension type aerosol, and discover the key prescription factors for reasonable control. Of course, the above prescription factors may have a direct impact on other quality attributes of inhaled aerosols. For example, different propellants have different vapor pressures, different proportions of propellants, and different proportions of ethanol and propellants, which have a direct impact on the particle size distribution of the droplets. And the aerodynamic droplet distribution has a direct impact, and it may also have a greater impact on other quality attributes; the amount of ethanol and propellant affects the concentration of the drug solution and affects the content of each qin; the stabilizer has a direct impact on related substances, etc. Prescription development is a process of simultaneous research and evaluation of multi-factors and multi-preparation quality attributes. It needs to be considered and researched systematically. If necessary, the prescription can be studied through DOE.
The quality attributes of inhaled aerosols are affected by many factors, and it is difficult to develop them. In addition to the above-mentioned prescription factors, tanks, valves and actuators have an impact on the droplet size distribution and aerodynamic droplets of inhaled aerosols. Quality attributes such as distribution, impurities (including extracts), leakage, homogeneity of each compound, and appearance of the liquid medicine may have a great influence. Therefore, research should be carried out simultaneously when formulating the formulation.
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