Granulating Technology Development for Traditional Chinese Medicine
Writer： admin Time：2021-04-22 17:12 Browse：℃
Processing technologies for traditional Chinese medicine production include fore-treating, extracting, condensing, mixing, drying and granulating. For higher granule quality and guaranteed clinical effect, pharmacy workers carry out extensive experiments and studies on granulating techniques and parameters. For example, better excipients and innovated techniques can be adopted to improve granule quality during granulation. Application of new granulating technologies can greatly improve production speed and quality of traditional Chinese medical granules.
1. Wet granulation for Chinese traditional medicine
Wet granulation was the most commonly-used technology for traditional Chinese medical tablet and powder preparation in1950s. From the perspective of modern preparation requirements, traditional techniques have obvious insufficiency mainly in that its excipients are confined to sugar powder, starch, dextrin and so on. Among them, sugar powder is strong in absorbing moisture, starch will be hydrolyzed and not expand when it reacts with acid and alkali or is dampened or heated, and dextrin will interfere some medicine’s content determination so it’s not an appropriate filler. In addition, traditional technique operators rely more on their experience of extract proportion and consistency to determine excipients’ dosage which furthermore influences preparation quality control. What’s more, granules made from hygroscopic API and excipientswill block and adhere to the screen so that the they are too hard but of poor solubility, unstable quality, high substandard rate and low end product yield.
(Mixing blade and granulating knife on wet granulation machine)
In China, researchers also carry out an orthogonal experiment on sugar-free powder preparing techniques with soluble starch as excipient and sodium cyclamate as taste corrector. It is found that the proportion of traditional Chinese extract, soluble starch and sodium cyclamate at 1:2:0.025 is the most proper granulating parameter. On the other hand, single-factor and orthogonal experiment is used to find out the proper parameter for Shengmaiyin capsule (a kind of Chinese patent medicine): lactose as diluent, proportion between lactose, MCC and Magnesium Trisilicate at 12:5:3, 5% PVP solution as adhesive and mixing time for 150s. In addition, different excipientsare tested depending on the moisture absorbing rate and fluidity, and critical relative humidity (CRH) are further assessed. The result shows that MMC as excipient can improve not only preparation’s stability and fluidity but also its dissolution rate.
The researchers also find that two-step drying, i.e., a combination of dynamic drying and static drying, can be applied in wet granulating and drying to shorten drying time and improve production efficiency. Its procedures are as follows: firstly, dynamic drying, sieving, drying wet granules with fluid-bed dryer for 10min and sieving; secondly, static drying the granules with hot-wind recycling oven.
2. Dry granulation for Chinese traditional medicine
Dry granulation is a new technology in recent years. It is mainly finished in rotary compressor or roller compressor. Its advantages are that traditional Chinese medical extract can be granulated directly after being added with proper exceptions without wetting, mixing and drying. The process is quite simple to guarantee medicine quality effectively.
(Powder collecting cloth bag on fluid bed drier)
Recently, researchers have developed many types of new exceptions including pregelatinized starch, mannitol, lactose, water-soluble acrylic resin, cellulose derivatives and spared no effort in experimenting dry extract and exceptions proportion. For example, there is an experiment result for cough and asthma granules. At first, extract is dried and 80% alcohol containing 10% L-HPC is used as adhesive with the proportion of extract powder, bifidosaccharide and soluble starch at 10:3:2. Then the material is mixed in the granulating machine for granules with uniform granularity and proper sweetness. The granules has weaker hygroscopicity， high concentration, low exceptions and low sweetness. Another orthogonal experiment is applied to study influence of temperature, water content and exceptions dosage on Radix Isatidis granule. The result shows that the influence of exceptions dosage is larger than that of water content, which is larger than that of temperature. Furthermore, the optimal technical parameter is that dextrin dosage is at 9%, water content at 4% and temperature at 20°C.
3. Fast Mixing granulation for Chinese traditional medicine
It refers to the granulating technology finished by mixing granulating machine. During production, the paddle and granulating knife rotates at the same time for 3D mixing, cutting and granulating. The mixed material is pretty uniform and will not block. As API and excipients are both fed into the same container of the machine, mixing, cutting, granulating and rolling are finished in one step. The end granules are of round shape, good fluidity and low excipient dosage and the whole process finishes in a closed container quickly without causing heavy pollution.
Chinese researchers also study the difference between Jiedaiting electuary (a kind of Chinese patent medicine) of oscillating granulation, mixing granulation and squeezing granulation in accordance to the result of optical microscopy, moisture absorption rate and dissolution rate. The result shows that 1) squeezing granulation is ranked first and followed by mixing granulation in granule bulk density, 2) oscillating granulation is the best and mixing granulating is better than squeezing granulation in dissolution rate and 3) oscillating granulation tops squeezing granulation which is then better than mixing granulation in moisture absorption rate. Comprehensively speaking, products of mixing granulation has good stability (i.e., proper moisture absorption rate) so that mixing granulation is appropriate for the granule production. And for Daijieting electuary production, the extracted Chinese patent medicine can be processed to extract with specific gravity of 1.2-1.4 and the end product can be produced by mixing and granulating extract, dextrin and starch in the ratio of 1.12:1:1 for 10 min. The researchers also optimize granulating technology and determine the optimal parameters by applying uniform design and non-functional data processing method. For example, when producing anti-virus traditional Chinese medical granule, the API can be extracted to extract with specific gravity of 1.19-1.32. Then the extract can be mixed and granulated with dextrin and residual material of the previous batch in the proportion of 8000ml:25kg. And the time can be only 1/3 of the former techniques (extracting - mixing - vacuum drying - granulating) and the quality is still guaranteed.
4. Spraying granulation for Chinese traditional medicine
It is also called fluid-bed granulation or one-step granulation, by which mixing, granulating and drying are finished in one step. Therefore, excipients can be used in less amount but the end granules are still of uniform size, round shape, good fluidity, good compressibility and high output. Besides, products are far away from contamination since they are just processed in a closed machine. Currently, spraying granulation is more used to produce sugar-free or low-sugar granules.
With fluid-bed spraying granulation, Yinqiao granules can be not only produced in less steps but also featured by loose and porous structure and thus tablets made from the granules are of high hardness, quick disintegration and improved quality. In addition, technicians adopt orthogonal experiment to determine the optimal parameter for Xiaochaihu (Common Goldenrop) granule production, i.e., mixing sucrose powder, corn starch and calcium hydrogen phosphate in the ratio of 1.3:1.1:1.4 for 5min, extracting and then producing the granules for tablet compression. Our spraying granulators can also produce other low-sugar products, such as Jingwu electuary with 40% lower sugar content and stable quality.
