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CN-121987580-A - Double-layer slow-release tablet and preparation method thereof

CN121987580ACN 121987580 ACN121987580 ACN 121987580ACN-121987580-A

Abstract

The application relates to the field of pharmaceutical preparations, in particular to a double-layer slow-release tablet and a preparation method thereof, wherein the double-layer slow-release tablet comprises a first tablet layer, a second tablet layer and a coating layer coated on the outer surface of the first tablet layer, the first tablet layer comprises fat-soluble vitamins and calcium carbonate particles and does not contain hypromellose, the second tablet layer comprises water-soluble vitamins, hypromellose and a colorant and does not contain calcium carbonate particles, and the hypromellose in the second tablet layer is a mixture of high-viscosity hydroxypropyl methylcellulose and low-viscosity hydroxypropyl methylcellulose. According to the application, through the synergistic effect of the double-layer sheet structural design and the step-by-step pressing process, the material fluidity of the first sheet is obviously improved, the problems of powder clamping and uneven filling are avoided, and through precisely controlling the difference value between the first pressure and the second pressure to be not lower than 20KN and combining an intermediate dust removal process, the clear parallelism of an interlayer interface is effectively ensured, and the common parting line inclination phenomenon of the traditional double-layer sheet is thoroughly eliminated.

Inventors

  • HUANG MIN
  • FENG LIPING

Assignees

  • 杭州高成生物营养技术有限公司

Dates

Publication Date
20260508
Application Date
20260306
Priority Date
20250516

Claims (10)

  1. 1. A bilayer sustained release tablet comprising a first tablet layer, a second tablet layer and a coating layer coated outside the first tablet layer, characterized in that: The first ply comprises fat-soluble vitamins and calcium carbonate particles and is free of hypromellose; The second sheet comprises water-soluble vitamins, hypromellose, and colorants, and is free of calcium carbonate particles; Wherein the hydroxypropyl methylcellulose in the second sheet layer is a mixture of high-viscosity hydroxypropyl methylcellulose and low-viscosity hydroxypropyl methylcellulose so as to provide a slow release effect.
  2. 2. A vitamin mineral direct compression bilayer tablet according to claim 1 wherein the vitamin mineral direct compression bilayer tablet comprises, The first sheet layer contains one or more of vitamin A and its derivatives, vitamin D and its derivatives, vitamin E and its derivatives, magnesium carbonate, calcium carbonate and manganese gluconate; the second sheet layer contains vitamin B and any one or a combination of a plurality of derivatives thereof, nicotinamide, folic acid, biotin, D-calcium pantothenate, calcium ascorbate, zinc organic acid, ferrous organic acid, copper organic acid and selenium-enriched yeast.
  3. 3. A vitamin mineral direct compression bilayer tablet according to claim 1 or 2 characterized in that, The first sheet layer also contains at least one or more of a binder, a glidant, a filler and a colorant.
  4. 4. A vitamin mineral direct compression bilayer tablet according to claim 1 or 2 characterized in that, The addition amount of the high-viscosity hydroxypropyl methylcellulose is larger than that of the low-viscosity hydroxypropyl methylcellulose.
  5. 5. A vitamin mineral direct compression bilayer tablet according to claim 4 wherein the vitamin mineral direct compression bilayer tablet comprises, The mass ratio of the high-viscosity hydroxypropyl methylcellulose to the low-viscosity hydroxypropyl methylcellulose is 3:1.
  6. 6. A vitamin mineral direct compression bilayer tablet according to claim 1 wherein the vitamin mineral direct compression bilayer tablet comprises, The mass of the coating layer is 2% -4% of the total mass of the first tablet layer and the second tablet layer.
  7. 7. A process for preparing a bilayer sustained-release tablet according to any one of claims 1 to 6 comprising the steps of, -Applying a first pressure to the first ply material after mixing thereof to form a first ply; -turning on the dust removing device to remove the dust on the surface of the first sheet; -applying a second pressure to the second sheet material after mixing it, forming a top layer; coating the first tablet layer and the second tablet layer to obtain the double-layer slow-release tablet, wherein, The first pressure is smaller than the second pressure, and the pressure difference between the first pressure and the second pressure is more than or equal to 20 KN.
  8. 8. The method of claim 7, wherein the step of determining the position of the probe is performed, The pressure of the first sheet material pressing is 5 KN-10 KN, and the pressure of the second sheet material pressing is 40 KN-60 KN.
  9. 9. The method of claim 7, wherein the step of determining the position of the probe is performed, And (3) carrying out three-dimensional mixing on the fat-soluble vitamin and the calcium carbonate particles for 25-35 minutes before pressing the first sheet layer.
  10. 10. The method of claim 7, wherein the step of determining the position of the probe is performed, The water-soluble vitamins and microcrystalline cellulose were mixed in equal increments prior to pressing the second tablet and, at each equal increment, sieved and mixed with a three-dimensional mixer.

Description

Double-layer slow-release tablet and preparation method thereof Technical Field The present application claims priority from chinese patent application 202510630227.2, filed 5, 16, 2025, the entire contents of the foregoing description are references to the present application. The invention relates to the field of pharmaceutical preparations, in particular to a double-layer slow-release tablet and a preparation method thereof. Background In the development of oral solid preparations, sustained-release tablets are attracting attention because of their ability to release active ingredients stably, reduce the number of times of administration and enhance the experience of patients, and are particularly suitable for vitamin complex preparations, which often require both stable delivery of fat-soluble and water-soluble ingredients. The double-layer tablet structure is used as a common technical proposal in the industry, and the release behavior can be optimized theoretically by separating materials with different properties, for example, the water-soluble vitamins which are easy to absorb moisture are isolated from hydrophobic auxiliary materials, so that mutual interference is avoided. However, in practical industrial production, such designs often face the additive effect of multiple challenges, resulting in unstable product quality or difficult process scale-up. Many enterprises have tried to deal with this by adjusting the types of excipients or optimizing tabletting parameters, but the effects tend to be out of phase and even cause new problems. Taking material fluidity as an example, when the formula contains a high proportion of inorganic filler (such as calcium carbonate), powder particles are easy to agglomerate due to static electricity or rough surface, so that the hopper of the tablet press is not smooth in blanking, and the difference of tablet weights exceeds the standard. Talcum powder or micro silica gel is commonly added in the industry as a glidant, but excessive use can weaken cohesion among particles, reduce the hardness of tablets and even influence the adhesive force of subsequent coatings. More particularly, when the density or particle size distribution of the two layers of materials is large, layering phenomenon is very easy to occur in the mixing process, so that water-soluble vitamins (such as riboflavin) are locally enriched, and finally, the content uniformity is disqualified, which is almost an obstacle which is difficult to surmount in a preparation with small dosage of high active ingredients. At the same time, the pressing process of the two-layer sheet itself has inherent drawbacks. The traditional method usually adopts single compression molding, but if the compression characteristics of upper and lower materials are not matched, interface blurring or inclined boundary lines are easy to occur. For example, when the slow-release layer contains a large amount of hydrophilic matrix material, if the bottom layer is not sufficiently pre-pressed, the high pressure of the upper layer can force the two layers to excessively fuse, damaging the design intention, whereas if the bottom layer is excessively pressed, moisture permeation can be blocked, and the slow-release effect can be affected. Some enterprises try to introduce a step-by-step pressing technology, namely, a bottom layer is pressed first and then an upper layer is overlapped, but in actual operation, interlayer binding force is often insufficient due to dust residues, microcracks are generated when the dust residues are light, and the dust residues are directly layered and fall off when the dust residues are heavy. Such defects not only affect product appearance identification (e.g., color demarcation), but are more likely to alter the drug release path. Although new auxiliary materials or intelligent process control systems are continuously explored in the industry, the existing scheme focuses on single pain points, and the cooperative consideration of material characteristics, structural design and process parameters is lacked. When multiple vitamins are required to coexist in the same tablet, how to ensure the controllable fluidity, clear layer boundary, stable release and standard appearance on the premise of not sacrificing the production efficiency becomes a key bottleneck restricting the product landing. Many developers are thus involved in repeated trial and error cycles, which are difficult to break through technical ceilings, and are also not subject to systematic breaches, so that the industrialization process of such high-value preparations is always laborious. Disclosure of Invention The application aims to overcome the comprehensive defects that in the prior art, the double-layer sustained-release tablet is difficult to synchronously solve the problems of insufficient material fluidity, interface blurring caused by unstable interlayer combination and difficult accurate regulation and control of the sustained-r