CN-122005478-A - Superfine powder tabletting preparation and preparation method thereof

Abstract

The invention provides an ultrafine powder tabletting preparation and a preparation method thereof, wherein the preparation method comprises the following steps of embedding a traditional Chinese medicine extract with hydrophobic mesoporous silica, spraying and coating an active core embedded with the hydrophobic mesoporous silica by using coating liquid formed by ferric ammonium citrate and a film-forming polymer to form FAC layer microspheres, coating the FAC layer microspheres with gallic acid-resistant starch composite coating liquid for the second time, irradiating ultraviolet light before the coating is finished to obtain MOG microspheres, and directly tabletting after the MOG microspheres are uniformly mixed with a filler, a disintegrating agent and a glidant to obtain the ultrafine powder tabletting preparation. The superfine powder tablet preparation prepared by the invention has good mechanical property, moisture resistance and colon targeting property, and fundamentally solves the technical problems of the superfine powder preparation in various aspects such as tablet forming, targeted delivery, physical stability and the like.

Inventors

• ZHANG JIHONG
• LI MINGZE
• QIN FEI
• Xie Yaqiong
• YANG FAJUN
• HUANG YULONG
• LI YAOHUI
• Sun Xiazhi
• ZHANG FANG

Assignees

• 甘肃省农业科学院农产品贮藏加工研究所

Dates

Publication Date

20260512

Application Date

20260120

Claims (9)

1. 1. The preparation method of the superfine powder tabletting preparation is characterized by comprising the following steps of: s1, dissolving polyvinylpyrrolidone-vinyl acetate copolymer PVP-VA and ferric ammonium citrate FAC in an ethanol water solution, and filtering with a filter membrane to obtain FAC-PVP-VA coating liquid; S2, loading TCME-MSNs nano particles into a fluidized bed hopper, spraying and coating FAC-PVP-VA coating liquid, and continuously fluidizing and drying after coating is finished to prepare FAC layer microspheres; s3, dissolving gallic acid in ethanol water solution, adding resistant starch into water, stirring and gelatinizing in a high-temperature water bath, cooling, adding into gallic acid solution under strong stirring, and uniformly mixing to obtain gallic acid-resistant starch composite coating liquid; S4, reloading the FAC layer microspheres prepared in the step 2 into a fluidized bed, spraying and coating the gallic acid-resistant starch composite coating liquid, starting an ultraviolet irradiation system at the top of the fluidized bed before spraying is finished, adjusting the illumination intensity to ensure to cover the whole fluidized bed material area, continuously keeping fluidization and illumination after spraying is finished, and finally turning off illumination, and continuously fluidizing and drying to prepare MOG microspheres; S5, uniformly mixing the MOG microspheres, the filler, the disintegrating agent and the glidant, and directly tabletting to prepare the superfine powder tabletting preparation.
2. 2. The method of claim 1, wherein the mass ratio of PVP-VA to FAC in the step S1 is 2-4:1-8.
3. 3. The preparation method of the TCME-MSNs nanoparticle according to claim 1, wherein the preparation method of the TCME-MSNs nanoparticle in step S2 comprises the following steps: S21, adding water into the traditional Chinese medicine materials according to a mass ratio of 1:4-10, decocting for 1-3 hours, filtering and collecting filtrate, repeatedly extracting for 1 time, combining the filtrates, concentrating to a relative density of 1.19-1.21, drying at 45-50 ℃, and then carrying out superfine grinding to obtain a traditional Chinese medicine extract TCME; S22, dispersing mesoporous silica nano particles MSNs in DMSO, adding eicosanoids, adding EDC and NHS, reacting for 30-50 hours at 70-75 ℃, centrifuging, washing the precipitate with absolute ethyl alcohol, and preparing the hydrophobized MSNs; S23, adding the traditional Chinese medicine extract TCME into absolute ethyl alcohol, performing ultrasonic dispersion, adding the hydrophobized MSNs in a stirring state at 50-60 ℃ for multiple times, continuously stirring for 2-5 hours after the addition, then performing rotary evaporation on a mixed system to remove the ethanol, and performing vacuum drying overnight to obtain the TCME-MSNs nano particles.
4. 4. The method of claim 1, wherein the ratio of TCME-MSNs to FAC-PVP-VA coating solution in the step S2 is 1-2:15-40.
5. 5. The method of claim 1, wherein the mass ratio of gallic acid to resistant starch in step S3 is 1-2:1.2-2.5.
6. 6. The preparation method of the gallic acid-resistant starch composite coating liquid is characterized in that the mass-volume ratio of the FAC layer microspheres to the gallic acid-resistant starch composite coating liquid in the step S4 is 1:15-25, the balance of the gallic acid-resistant starch composite coating liquid before the end of spraying is 10-15%, and the illumination intensity is 10-30 mW/cm 2 .
7. 7. The preparation method of the superfine powder tablet preparation according to claim 1, wherein the superfine powder tablet preparation in the step S5 comprises, by weight, 10-25% of MOG microspheres, 20-55% of a filler, 3-15% of a disintegrating agent and 1-5% of a glidant.
8. 8. The method according to claim 1, wherein the filler in the step S5 is one or more of lactose, microcrystalline cellulose, mannitol and starch, the disintegrating agent is one or more of povidone, croscarmellose sodium, sodium carboxymethyl starch and hydroxypropyl methylcellulose, and the glidant is one or more of magnesium stearate, calcium stearate and talcum powder.
9. 9. The ultrafine powder tabletting preparation prepared by the preparation method according to any one of claims 1 to 8.

Description

Superfine powder tabletting preparation and preparation method thereof Technical Field The invention belongs to the technical field of drug tabletting, and in particular relates to an ultrafine powder tabletting preparation and a preparation method thereof. Background As one of the most commonly used dosage forms, the conventional preparation process (such as wet granulation, dry granulation followed by tabletting, or powder direct tabletting) exposes the following systematic technical bottlenecks when dealing with the requirements of modern functional foods and novel drug delivery, especially when dealing with highly active, unstable ingredients that require colon targeted release: 1. The stability of the active ingredient is inherently contradictory to the processing of the formulation in that many functional plant extracts, probiotics, polypeptides, unsaturated fatty acids, etc. are sensitive to heat, and traditional crushing, granulating, drying and certain coating procedures may generate local high temperatures, resulting in inactivation, degradation or oxidation of the active ingredient. To increase bioavailability, it is often necessary to micronize or even nanocrystallize the active ingredient, but the resulting high specific surface area and high surface energy, exacerbate moisture absorption, agglomeration, form transformation and chemical degradation of the ingredient. Uniform mixing of low-dose high-activity components and a large amount of auxiliary materials is a key for ensuring the content consistency of each tablet, and superfine powder is easy to generate static electricity and agglomeration, so that uneven mixing and content difference are caused, and the traditional mixing process has limited control. 2. The colon targeted release system has insufficient reliability, coating materials (such as acrylic resin) which depend on the pH difference between the stomach and the colon, release of the coating materials is influenced by the fluctuation of the pH value of the gastrointestinal tract of an individual and food, the problems of premature release in the stomach or incomplete release in the colon are easy to occur, and the targeting accuracy is poor. The delayed release system is realized by controlling the erosion time of the coating layer, the release behavior of the delayed release system is greatly influenced by physiological factors such as gastric emptying time, intestinal peristalsis and the like, the individual difference is obvious, and the release time point is difficult to accurately control. Although the utilization of colonic flora specific enzyme is an ideal targeting strategy, the enzymolysis rate of the existing carrier (such as pectin, chitosan and other polysaccharide) is slow, the specificity is limited, the mechanical strength and the moisture resistance of the carrier after film formation are often insufficient, and the requirements of a tabletting process and the long-term stable protection of contents are difficult to meet. 3. The comprehensive defect of the preparation performance is that a thick coating or hydrophobic material is often required to ensure the stability of the tablet during storage, but the disintegration and dissolution of the tablet at a target position are often delayed or even hindered, and the efficacy is affected. Many advanced drug delivery systems such as microcapsules, liposomes and the like in the prior art are fragile, and are easy to collapse in structure and rupture in capsule wall under high pressure of direct compression, so that the active ingredients are exposed and the controlled release function is lost. Coated pellets or granules prepared for colon targeting may have surface properties that are detrimental to flow, resulting in uneven filling during tableting, large tablet weight differences, and the need to add large amounts of glidants to dilute the active ingredient or introduce unnecessary excipients. In summary, developing a technology capable of synchronously solving the problems of activity protection, accurate targeting, good tabletting property and process controllability is a key to the urgent breakthrough in the fields of current functional foods and novel oral pharmaceutical preparations. The prior art solutions often only focus on solving one or two of the problems, but cannot achieve synergistic optimization at multiple levels of molecular, microstructure and macroscopic properties. Therefore, a new formulation design concept and preparation process are urgently needed to overcome the comprehensive pain existing in the background technology. Disclosure of Invention Aiming at the core technical problems of insufficient mechanical strength and poor physical and chemical stability (easy moisture absorption, agglomeration and degradation) of superfine powder/nano active ingredients in direct tabletting in the prior art, the invention aims to provide a superfine powder tabletting preparation and a preparation method there