Preparation method of semisolid preparation for psoriasis treatment

Abstract

The invention relates to a preparation method of a semisolid preparation for psoriasis treatment; the preparation method comprises the specific steps of 1) adding a mixture of tacalcitol 1-5 ppm of total weight of the semisolid preparation and a therapeutically effective amount of corticosteroids into a matrix accounting for 2-40% of the prescription amount, and stirring and mixing; 2) stirring the remaining prescription amount of the matrix and other medicinal excipients under the protection of gas at the temperature of 60-90 DEG C and in a nitrogen-oxide molar ratio of not less than 3.7; 3) combining the mixtures of steps 1) and 2), and stirring and mixing under the protection of gas at the temperature of 60-90 DEG C and in a nitrogen-oxygen molar ratio of not less than 3.7 to obtain the semisolid preparation mixed well. The preparation method of the semisolid preparation for psoriasis treatment has the advantages that equipment requirements in the preparation process can be lowered, the complex preparation process is simplified, and the preparation time of the semisolid preparation is shortened at the premise of ensuring the distribution uniformity of active matters in the semisolid preparation.

Description

Technical field [0001] The invention relates to a preparation method of a pharmaceutical preparation, in particular to a preparation method of a semi-solid preparation for the treatment of psoriasis. Background technique [0002] Psoriasis, also known as psoriasis, is a chronic inflammatory skin disease. It lasts for a long time and is prone to recurrence. In some cases, it will not heal for almost a lifetime. Its incidence is mainly young and mature, and it affects the physical health and mental state of patients. Affected; clinically often symptoms such as erythema and scaly, the disease can occur throughout the body, with the scalp and limbs more extended, which is easy to aggravate in winter; the current treatment of psoriasis mainly includes vitamin D derivatives and corticosteroids Corticosteroids, tretinoin, anthracene, keratin exfoliants, etc.; corticosteroids are steroids produced by the adrenal cortex, mostly hormones, such as glucocorticoids and mineralocorticoids; in ...

AI Technical Summary

Problems solved by technology

[0003] Vitamin D derivatives have high activity, so the content of their preparations is very low, usually between 0.0001 and 0.0005%, and it is not easy to mix well during the preparation process; moreover, vitamin D derivatives themselves have the characteristics of light instability and easy oxidation Therefore, while ensuring the uniformity of trace active substances in the matrix, ensuring its stability in the preparation process and long-term stability in the preservation process will make the preparation of vitamin D derivative semi-solid preparations very difficult put into practice

[0004] In order to solve the above problems, the commonly used method is the equal-volume incremental method, that is: after the active ingredient is finely ground, add the same amount of matrix and mix well, then add the same amount of matrix as the mixture and mix well, repeat this operation until all components The mixing is completed, and the entire mixing process requires vacuum or nitrogen; although this method can ensure the uniformity and stability of trace active ingredients in semi-solid preparations, due to the very low content of active ingredients, the difference in the content of active ingredients and matrix in the preparation The difference is that the number of repeated additions of the matrix is ​​as many as 8,000 times, and there will be problems in production such as cumbersome steps, long production time, complicated process control, and doubled consumption of equipment and labor costs; moreover, cumbersome production steps and excessively long production time, leading to the decline of active ingredients and the generation of impurities; for drugs, the decline of active ingredients will affect the effectiveness of drugs; the generation of impurities will affect the safety of drugs

[0005] Patent CN201510208126.2 discloses a vitamin D and corticosteroid multi-microbubble topical composition and its application and manufacturing method: under suitable conditions, the hydrophilic solvent is mixed with the hydrophobic solvent to form Said composition comprising at least one polyaphron dispersion, at least one vitamin D or vitamin D analogue and at least one corticosteroid; which discloses a polyaphron dispersion difficult to address semi-solid formulation field The mixing stability, effectiveness and technical difficulties caused by impurities, and it is also difficult to transfer technology for reference

[0006] Patent CN200480013008.6 describes another method for preparing a preparation containing a trace amount of active ingredient, the method is: weighing the active ingredient in a container coated with petrolatum, encapsulating the active ingredient in the excess petrolatum, adding the active ingredient The container of vaseline and vaseline is introduced into the mixer, and the active ingredient is dispersed in the mixer; this scheme has the following disadvantages: 1. the requirements for mixing equipment are very high (see accompanying drawings 1 to 9 of patent CN200480013008.6), and not only Stainless steel conical frustum, complex equipment such as a sealing cover is also required; the weighing container in step 1) has a complex structure, and there is a grid at the end of the container. At the same time, it needs to be equipped with a lock to combine with the mixer used in step 3); the mixer used in step 3) and step 4) needs to be equipped with a certain height of rod and lock to drive the weighing container encapsulated with active ingredients It can be seen from the accompanying drawings 2 to 9 of this patent CN200480013008.6 that the structure of the mixing equipment of this patent is complicated, and the production equipment needs to be specially customized, which is not conducive to industrial production, and greatly increases the production cost and operating cost; ② mixing Long homogenization time: Although the mixing time of this solution is slightly shorter than that of the equal-volume incremental method, it still needs to disperse a small amount of active substances into a large number of substrates until uniform. In the preferred embodiment disclosed in the patent specification, the homogenization temperature 70~90°C, the mixing time is as high as 3.5h to 4.5h; for vitamin D derivatives that are unstable to light and heat, mixing at 70~90°C for 3.5~4.5h may cause decomposition of active substances and appearance of impurities risk

Or the operation steps are complicated, the process control is cumbersome, the method is difficult to scale production, and it is difficult to ensure the effectiveness and safety of the preparation

Or the structure and configuration of mixing equipment is complex, which is completely different from the equipment used in general semi-solid preparations in the pharmaceutical industry. It needs to be customized and operated separately, and the production and operation costs are high.