Preparation method of inhalation dry powder composition

Abstract

The invention relates to a preparation method of an inhalation dry powder composition. The method comprises the following steps that 1, a lubricant and a medicinal carrier are subjected to first shearmixing to obtain a carrier compound; 2, the carrier compound in the step 1, a long-acting cholinergic receptor blocking agent and a long-acting beta receptor stimulant are subjected to second shear mixing, so that the inhalation dry powder composition is obtained.

Description

technical field [0001] The invention belongs to the technical field of pharmaceutical preparations, and in particular relates to a method for preparing a dry powder composition for inhalation. The dry powder composition contains a long-acting cholinergic receptor blocker and a long-acting β-receptor agonist, which can be injected into the drug through a dry powder inhalation device. Pulmonary administration. Background technique [0002] Long-acting cholinergic receptor blockers and long-acting beta-agonists are common drugs used to treat COPD. Long-acting cholinergic receptor blockers can bind to acetylcholine receptors and β receptors, thereby inhibiting bronchial tone mediated by choline transmitters, and can also block the bronchoconstriction reflex mediated by the vagus nerve. Long-acting β-receptor agonists can bind to β-receptors, increase the level of cyclic adenosine monophosphate (cAMP), relax the tracheal smooth muscle, and may also reduce the release of mast cel...

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Problems solved by technology

[0007] However, in practical application, it is found that the existing technical solutions have certain defects, which will lead to higher industrial production costs of products or shorter validity periods of products.

For example, the fluidity of the composition will be greatly reduced after adding an excessive amount of fine carrier components, thereby affecting the uniformity of subsequent filling and mixing, and increasing the product fine particle delivery fraction (FPF) is not effective; use a large amount of lubricant, and Although the method of mixing the two active ingredients with the lubricant using high-energy mixing methods (such as co-micronization and mechanical fusion) reduces the force between the particles and increases the product fine particle delivery fraction (FPF), the amount of lubricant The use may affect the safety of the drug, and long-acting cholinergic receptor blockers belong to the tropane class of drugs, most of which are alkaloids formed by condensing amino alcohols derived from tropane and other organic acids into esters. Because the ester bond is easy to be hydrolyzed and unstable, the local high temperature formed during co-micronization with lubricant and mechanical fusion will aggravate this change, resulting in the increase of related substances in the preparation product and shortening the validity period of the product; while using three-dimensional mixing, When mixing methods such as V-type mixing, due to the low dispersion efficiency of the equipment for fine particles, on the one hand, the fine particle delivery fraction (FPF) of the product is not good, and on the other hand, it requires a long mixing time, which greatly increases labor and other costs.

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