1. grinding method
Suitable for the preparation of oily base ointment. A method for preparing ointment by directly grinding and mixing semi-solid oily matrix and fine sieve powder. The preparation method comprise grinding that medicine, sieve, grinding with the same amount of matrix, adding the remaining matrix into the total amount, and grin. The method is suitable for preparing a small amount of ointment, and the drug is insoluble in the matrix. When prepared in the laboratory, it can be ground in a mortar; It can be produced in large quantities and prepared by electric mortar.
2. Emulsification method
Is suitable for preparing emulsion ointment. The oily and oil-soluble components in the prescription are heated to 80 DEG C together to form an oil solution; In addition, water-soluble components are dissolved in water and heated to about 80℃ to form an aqueous solution. When the two phases are mixed, the temperature of the water phase is slightly higher than that of the oil phase to prevent the solid components in the oil phase from precipitating or condensing prematurely. Gradually add the water phase into the oil phase, stirring while adding until the water phase condenses. In mass production, when the temperature is reduced to 30℃, colloid mill or ointment mill will be finer and more uniform.
There are three ways to mix oil and water by emulsion method: ① two phases are mixed at the same time, which is suitable for large-scale mechanized operation; (2) The dispersed phase is added to the continuous phase, which is suitable for emulsion systems containing small dispersed phase; (3) continuously added to the dispersed phase, suitable for most emulsion systems. For example, when preparing an O/W cream base, the water phase is slowly added to the oil phase with stirring, and the amount of the water phase is initially less than that of the oil phase, thereby forming a W/O emulsion. When the water phase is continuously added into the oil phase, the Mongolian number of the emulsion continues to increase until the volume of the water phase of the W/O emulsion increases to the maximum. Beyond this limit, the Mongolian number of the emulsion decreases and the emulsion is transformed into an O/W emulsion, so that the internal phase (oil phase) is formed.
There are three emulsifying machines for emulsification: emulsifying machine, colloid mill and homogenizer.
Factors affecting the quality of emulsion matrix: ① the influence of equipment stirring speed, such as too low stirring speed, can not achieve the purpose of full integration, too high stirring speed, will bring bubbles into the system, make it a three-phase system, and make the emulsion unstable; (2) The influence of emulsification temperature depends on the melting point of high melting point substances contained in the two phases. On the other hand, in the process of emulsification, the viscosity of the matrix will increase a lot. Increasing the temperature and reducing the porosity are beneficial to the uniform mixing of matrix components, which is generally controlled between 75-85℃. If there is phase inversion tear, the emulsification temperature should be controlled near the phase inversion temperature; ③ The influence of emulsification time should be determined according to the volume ratio of oil phase to water phase, Mongolia degree of two phases, viscosity of emulsion, type and dosage of emulsifier and emulsification temperature. In practical work, emulsification time is closely related to the efficiency of emulsification equipment. For example, it only takes 3- 10 minutes to emulsify with a homogenizer (3000 rpm).
3. Melting method
Suitable for the preparation of oily matrix. When the matrix formula contains high melting point components, it cannot be mixed evenly at room temperature. Melting method: firstly, the substrates with higher melting points, such as beeswax (62-67℃), paraffin wax (48-58℃) and stearic acid (55-60℃), are melted, then they are added in sequence according to the melting point, and stirred and mixed evenly until they are coagulated. If the prepared ointment is not fine enough, it needs to be further ground with a grinder to make it have no graininess.
The following are the requirements for ointments in Pharmacopoeia 20 15, Part IV 0 109:
Ointment refers to a uniform semi-solid external preparation made by mixing raw materials with oily or water-soluble matrix.
Due to the different dispersion States of raw materials in the matrix, they are divided into solution ointment and suspension ointment. Solution ointment is an ointment made by dissolving (or melting) raw materials in matrix or matrix components; Suspension ointment is an ointment made by uniformly dispersing fine powder of raw materials in matrix.
Cream refers to a homogeneous semi-solid preparation formed by dissolving or dispersing raw materials in emulsion matrix.
Cream can be divided into oil-in-water cream and water-in-oil cream because of different substrates.
Ointment and cream shall meet the following requirements during production and storage.
1. cream and cream matrix should be selected according to the characteristics of each dosage form, the nature of raw materials, the curative effect of the preparation and the stability of the product. Matrices can also be composed of different types of matrices.
Ointment matrix can be divided into oily matrix and water-soluble matrix. Commonly used oily substrates include vaseline, paraffin, liquid paraffin, silicone oil, beeswax, stearic acid, lanolin and so on. The water-soluble matrix mainly includes polyethylene glycol. Emulsifiers commonly used in cream can be divided into oil-in-water type and water-in-oil type. The oil-in-water emulsifier includes sodium soap, triethanolamine soap, sodium fatty alcohol sulfate and polysorbate; Water-in-oil emulsifier includes calcium soap, lanolin, monoglyceride, fatty alcohol, etc.
Two, ointment, cream matrix should be uniform, delicate, coated on the skin or mucous membrane should be non-irritating. Insoluble raw materials in ointment should be made into fine powder in advance by appropriate methods to ensure that the particle size meets the requirements.
3. Moisturizers, bacteriostats, thickeners, diluents, antioxidants and transdermal enhancers can be added to ointments and creams as required. Unless otherwise specified, when determining the formula of ointment and cream containing bacteriostatic agent, the bacteriostatic effect of the formula shall conform to the provisions of the method for testing bacteriostatic effect (general rules 1 12 1).
Four. Ointment and cream should have proper viscosity, be easily applied to skin or mucous membrane, and not melt, and the viscosity does not change much with the seasons.
Five, ointment, cream should be free of rancidity, odor, discoloration, hardening and other deterioration phenomena. The cream must not have oil-water separation and flatulence.
Six, unless otherwise specified, ointment should be sealed and kept away from light. Cream should be stored in a dark seal below 25°C and should not be frozen.
Seven, ointment, cream used in the inner packaging materials, should not be physical and chemical reaction with raw materials or matrix, aseptic products of the inner packaging materials should be sterile. Ointments and creams used for burn treatment, if they are non-sterile preparations, should be marked as "non-sterile preparations" on the label; The product manual should indicate that "this product is a non-sterile preparation", and at the same time, it should be clearly stated that "it is used for mild burns (I or shallow II)" under indications. Under the precautions, it is stipulated that "it should be used according to the doctor's advice".
Unless otherwise specified, ointments and creams should be inspected as follows.
Unless otherwise specified, the particle size of suspension ointment and ointment containing fine powder of decoction pieces shall be checked according to the following methods and meet the requirements.
Test method: Take a proper amount of test sample, put it on a glass slide and coat it into a thin layer. The area of the thin layer is equivalent to the area of the cover glass. * * * Take 3 pieces, and according to the particle size and particle size distribution determination method (the first method of General Rule 0982), no particles larger than 18CVm can be detected.
The loading quantity shall be inspected according to the minimum loading quantity inspection method (general rule 0942) and shall comply with the regulations.
Sterile ointments and creams used for burns [except mild burns (I degree or shallow II degree)] or severe wounds shall be inspected according to the aseptic inspection method (general rules 1 10 1) and shall comply with the regulations.
Unless otherwise specified, microbial limit inspection for non-sterile products: microbial counting method (general rules 1 105), control bacteria inspection method (general rules 1 106) and microbial limit standard for non-sterile drugs (general rules 1 107)