Traditional Chinese medicine pills refer to spherical or quasi-spherical dosage forms made from finely powdered medicinal materials or extracts combined with suitable binders or other excipients. Traditional Chinese medicine pills are an ancient dosage form that originated in the pre-Qin period and has continuously developed and enriched through the Han, Ming, and Qing dynasties to meet the needs of disease treatment. The manufacturing process has gradually improved, leading to various forms such as honey pills, wax pills, coated pills, and wax shell pills. In modern times, with advancements in pharmaceutical machinery, traditional Chinese medicine pills have continued to innovate and have become the main dosage form for mass-produced Chinese patent medicines.
History of Pills
In traditional Chinese medicine, pills refer to spherical or quasi-spherical dosage forms made from finely powdered medicinal materials or extracts combined with suitable binders or other excipients, primarily for internal use. Compared to decoctions and powders, traditional water pills, honey pills, paste pills, and wax pills dissolve slowly in the gastrointestinal tract after ingestion, exerting their effects gradually but lasting longer, thus they are often used for the treatment of chronic diseases. As Li Dongyuan said: “Pills are slow; they cannot quickly eliminate diseases but treat them gently.” Pills are solid forms that are convenient for patients to take and can mask the unpleasant taste of medicines. Additionally, some toxic or irritating substances in traditional Chinese medicine can be formulated into paste pills or wax pills using excipients to delay absorption and reduce toxicity and adverse reactions. Pills can also utilize various coatings to disintegrate at predetermined times in different parts of the digestive tract, providing a milder and more prolonged therapeutic effect than decoctions. Furthermore, pills are easy to carry and store. To better inherit this traditional dosage form and guide the reform of pill formulations, it is necessary to conduct in-depth investigations into the historical origins of traditional Chinese medicine pills.1. Origin of Traditional Chinese Medicine Pills Pills are one of the traditional dosage forms in Chinese medicine. The Ming dynasty’s Luo Gu recorded in “Wuyuan · Jiyuan” that “Xuanyuan’s minister Wu Peng first made medicinal pills,” tracing the history of pills back to approximately the 22nd century BC during the early slave society, which is certainly a folk legend and not necessarily reliable. The method of taking medicinal materials, after chewing, was to grind them into powder with primitive tools, which is the powder form. If fresh materials were used, they could be shaped into pills, and some liquid food could be used as a binder, gradually forming pills. The initial purpose of this was mainly for convenience in measurement, as the dosage of medicine is crucial for treating diseases. The medical book “Fifty-Two Disease Formulas” unearthed from the Han dynasty tomb of Mawangdui in Changsha, Hunan Province in 1973 records the names, prescriptions, specifications, dosages, and methods of taking pills. Many prescriptions in the book mention the preparation of pills, including those made with wine, vinegar, and oil, but do not involve specific methods for preparing pills. For example, “Take a large one, pound it with spring, and mix it with fat to make a large pill, using the original materials of Yebin, Fangfeng, Wuhua, and cinnamon, soak it in pure wine and swallow it as large as black beans.” It is noted that the size of the pills varied, with some as large as “infant peaches” and others as small as “red beans.” The famous physician Zhang Zhongjing’s “Treatise on Febrile and Miscellaneous Diseases” first recorded the use of animal glue (such as tortoise shell decoction), honey (such as hemp seed pill), and starch paste (such as snake bed powder) as excipients for pills. Before this, most pills were made using the properties of the medicinal materials themselves. Zhang Zhongjing was one of the first to propose adding viscous substances that do not affect the efficacy of the medicine to prepare pills. This book also introduces methods for taking pills, which can be taken with wine (such as kidney qi pills), boiled soup (such as Lichong pills), or swallowed with water (such as hemp seed pills), and can also be decocted and then taken as medicinal juice, such as Dida pills. The specifications for pills are also stipulated in “Treatise on Febrile and Miscellaneous Diseases,” with sizes such as “as large as a wutong seed” (like plum pills), “as large as a bullet” (like yam pills), “as large as a chicken egg” (like Lichong pills), “as large as a small bean” (like rhubarb and insect pills), and “as large as rabbit droppings” (like cinnamon and poria pills). The pills used by Zhongjing were produced according to the needs of the disease, and different excipients could be selected based on the condition, making the pills more distinctive. For example, the ginger and ginseng half summer pill used for treating persistent vomiting in pregnant women is made with fresh ginger juice to enhance its ability to dispel cold and stop vomiting. The bamboo skin pill used for treating postpartum vomiting is made with jujube flesh to harmonize the stomach qi. As stated in the “Golden Cabinet Classic”: “If you want to treat diseases, you should first use decoctions to wash the five internal organs… then use powders… and finally use pills, which can dispel cold, break accumulations, dissolve hard lumps, promote drinking and eating, and regulate the defensive and nutritive qi, which can be said to be the best method.” Additionally, Zhongjing determined the dosage of pills based on factors such as gender, age, physical strength, and severity of the condition, reflecting the TCM principle of individualized treatment and syndrome differentiation. The “Nourishing Life Formulas” unearthed at the same time contains more refined pills than those in the “Fifty-Two Disease Formulas,” with more excipients, and has begun to use honey and jujube paste to make pills: “Non-cheap, Fang Kui, Shih Wei, and Jiegeng, each a small bundle, three hawthorn seeds… five inches long, white snake if the green snake is three or four inches long, if… each is refined, and mixed with honey or jujube paste to make pills as large as sheep droppings.” This also marks the first recorded use of honey pills in the history of Chinese medicine. The “Nourishing Life Formulas” also lists excipients for pills, including sparrow egg juice, pine resin, animal blood, and horse paste. The “Huangdi Neijing,” written around the Qin and Han dynasties, records “Four black fish bones and one barley pill” (barley refers to madder): “Combine the two and make pills as large as small beans, taking five pills after meals, drinking with abalone juice.” This is the first time that pills made with protein as a binder are mentioned. The term “pill” first appeared in the “Records of the Grand Historian: Biography of Bian Que and Cang Gong.” The “Shennong Bencao Jing” Volume 1 “Preface” states: “Medicinal properties are suitable for pills, powders, decoctions, wine soaking, and paste boiling, and some can be used in multiple forms, while others cannot be used in decoctions or wine, depending on the medicinal properties, and must not be violated.” It can be seen that the earliest existing literature mentioning pills as a dosage form is in the “Huangdi Neijing,” and the earliest theoretical discussion about pills is found in the “Shennong Bencao Jing.” In addition, the term “pill medicine” also appears in the “Shennong Bencao Jing: Cow Horn and Gills”: “For blood stasis, pain, and women’s discharge of blood. Marrow: tonifies the center and fills the bone marrow. Long-term use increases longevity. Gall: can be made into pills.” 2. Development of Traditional Chinese Medicine Pills In the Jin dynasty, Ge Hong’s “Emergency Prescriptions for the Afterlife” initiated the use of binders that have both adhesive and therapeutic effects, such as “Another formula, chicken comb blood mixed with real vermilion, made into pills as small as beans, taken in the mouth, three or four pieces.” The chicken comb blood serves as both a binder and has certain medicinal effects. The “Emergency Prescriptions for the Afterlife” Volume 4 “Treatment of Febrile Diseases and Seasonal Illnesses” records honey wax pills: “If diarrhea cannot be eaten, one sheng of Huanglian, twenty pieces of Wumei, roasted and dried, then ground into powder, wax as large as chess pieces, one sheng of honey, mixed over low heat until it can be made into pills, pills as large as wutong seeds, take two pills each time, three times a day.” This is one of the earlier records regarding wax pills, providing experience for the later emergence of pure wax pills. At the same time, the “Emergency Prescriptions for the Afterlife” Volume 4 also discovered records of concentrated pills: “Another formula, take more branches and bark, boil down to make pills. Three pills as large as a chicken egg.” Moreover, concentrated pills appeared multiple times in the “Xiaopin Fang,” indicating that after the first appearance of concentrated pills in the “Emergency Prescriptions for the Afterlife,” they continued to develop and evolve in society. At that time, the “Wuwei Han Dynasty Medical Texts” recorded six formulas, most of which used honey for pills, such as: “Three parts of stone milk, one part of Ba Dou, and two parts of all three materials, all mixed into pills with honey as large as my real self, take three pills in the evening and swallow them in the morning.” This indicates that honey pills were already very popular in the Han dynasty and have been used to this day. An example of using pig fat for pills is: “For all diseases, the prescription for the plaster is one sheng of pepper, twenty fruits of the father pig fat, and three pounds of concentrated pills, which is the prototype of modern concentrated pills. The emergence and use of concentrated pills can save medicinal materials and improve efficacy. The “Xiaopin Fang” Volume 5 “Treatment of Diarrhea” records: “For ten materials, mix and grind, melt honey and gelatin together, and roll into pills.” This is the first time that the combination of gelatin and pills is recorded. There are also examples of using the marrow from sheep’s spine mixed with pig fat for pills, as well as several formulas using milk for pills. In the Tang dynasty, three special types of pills emerged: 1) Wax pills, which are made with beeswax as the base. This excipient is insoluble in water and acidic gastric juice, and only dissolves slowly in alkaline intestinal fluid, thus releasing the medicine gradually in the small intestine after oral administration, allowing for the adhesion of toxic substances like arsenic, preventing rapid absorption and avoiding the risk of poisoning; 2) Coated pills. The small red pills recorded in the “Secret Recipes for Healing” are coated pills; 3) Wax shell pills. Wax shells can serve a sealing function, as seen in the “Secret Recipes of the External and Internal Schools” Volume 31 “Pills from Various Families” which records the “Qili Jia Pills” made with wax wrapped around a pill as small as a bullet. This indicates that wax shell pills had already appeared at that time. The “Yixin Fang,” which draws heavily from Tang dynasty medical literature, also mentions pills wrapped in wax paper. The Tang dynasty had frequent exchanges with foreign regions, and maritime transportation was developed, leading to the introduction of various aromatic medicinal materials from the south. After preparing pills and powders, the aromatic components were easily lost, necessitating the use of wax to seal and preserve the original components. This indicates that the use of wax was already very common in the Tang dynasty. The “Jiyang Fang” contains a rich variety of excipients for pills, including honey pills, fat pills, glutinous rice paste pills, water pills, and cow bile pills, among others. Volume 3 “Treatment of Stomach Reflux” states: “Grind corn into powder, mix with water to make pills, as large as mulberry seeds, seven pieces.” This is the first known record of using pure water to make pills in Chinese medical literature. The famous physician Tao Hongjing of the Liang dynasty proposed the theory of pill application based on Zhang Zhongjing’s work: “Diseases that require pills, powders, decoctions, wines, or pastes should also consider the source of the disease for specific formulations.” This indicates that the use of pills requires two prerequisites: one is that the “medicinal properties” of certain drugs are suitable for making pills; the other is that the treatment of certain diseases is suitable for taking pills. The Tang dynasty saw a rich variety of pills, laying a solid foundation for the prosperity of pills in the Song dynasty and guiding the reform and development of pills in later generations. The rapid development of pills during the Han and Jin dynasties significantly increased the variety of excipients, with honey pills becoming widely used, and the clinical use of pills was not limited to specific diseases. The “Emergency Prescriptions for the Afterlife” made some regulations regarding the method of refining honey and the dosage of pills, such as: “All pill medicines should be as large as wutong seeds, for tonics, ten pills should be the starting dose, gradually increasing to no more than forty pills, as exceeding this may harm people.” It is worth noting that some excipients with obvious slow-acting effects, such as pine resin and beeswax, were used for pills. Although the number of formulas is not large, they represent an important leap. The “Emergency Prescriptions for the Afterlife” Volume 15 “Spleen Formulas: Cold Diarrhea” states: “Take five flavors of powder, melt with wax to make pills, the size of wutong seeds, take five pills, three times a day, no more than five or six doses.” This is the first known record of using only wax as an excipient for pills in Chinese medical literature. The variety of excipients for pills in this book is extensive, including honey, wax, pine resin, jujube flesh, cow bile, dog bile, wine, vinegar, syrup, sugar, saliva, and various other materials, totaling nearly forty types. The sizes of the pills varied, with some as large as chicken heads, others as large as bullets, and some as small as beans, peas, and grains. However, the pills in this book were not used solely for slow treatment, as they were also applied to conditions such as stroke, febrile diseases, difficult childbirth, bleeding, and breast pain, indicating that pills, especially honey pills, were also used for acute conditions. The “Emergency Prescriptions for the Afterlife” introduced a new dosage form similar to pills—medicinal beans, which is the first known record in Chinese medical literature. Medicinal beans are made by soaking beans in medicinal juice and then taking the beans for therapeutic purposes. This method opened up a new avenue for medication and provided a new idea for the creation of new dosage forms. The “Taiping Huimin Heji Ju Fang,” known as the first monograph on Chinese patent medicines, contains 788 formulas across 13 dosage forms, including decoctions, infusions, drinks, pills, powders, pastes, and granules, with pills accounting for 284 formulas, making up 36% of the total and ranking first among all dosage forms. The Song dynasty further developed two important types of pills: paste pills and water pills. Water pills are made from the original medicinal powder mixed with water, wine, vinegar, or other liquids, allowing for rapid absorption in the stomach. The absorption rate can vary depending on the excipient used, with wine as an excipient helping to dissolve alkaloids and volatile oils, while vinegar can also increase the solubility of alkaline components and promote gastric secretion, enhancing absorption. The “Xiaoer Yaozheng Zhijue” records the Baixiang pill: “Bake and dry to powder, make water pills as large as corn seeds.” Paste pills dissolve more slowly in the digestive tract than honey pills, and their absorption is correspondingly slower. Their absorption speed is related to the amount and viscosity of liquid in the digestive tract. Since paste pills release the medicine slowly, they prolong the duration of action and can avoid or reduce the irritation of certain medicines. For example, the “Jifeng Pujifang” records the Ou’er pill: “Right for fine powder, boiled with wine to make paste, as large as wutong seeds.” In the Song dynasty, the term “pill” was recorded in the “Bencao Yan Yi,” Volume 1 “Preface”: “Now, if mixed with honey, although easy to make pills, how can they be absorbed in the organs?” Although pills and pills are mixed terms, it indicates that the term “pills” had begun to appear and be used. The “Su Shen Neihan Liang Fang” pointed out: “Those with slow effects should use pills.” The “Zhen Zhu Nang Bu Yi Yao Xing Fu” stated: “Pills are slow.” This indicates that during the Song, Jin, and Yuan dynasties, pills were mostly used as important dosage forms for treating or regulating chronic diseases. In the Qing dynasty, based on the wax shell pills of the Tang dynasty, this excellent packaging form of ancient pills was further developed, and the production technology and methods for wax shell pills were detailed. For example, the “Complete Collection of Surgical Evidence” states: “Dry in the shade and wrap with yellow wax for preservation, breaking the wax shell when needed, and taking with aged wine.” Wax shell pills are still widely used today. The dosage forms of pills in the Ming and Qing dynasties were further improved based on previous foundations, laying the groundwork for the reform and innovation of pills in later generations. 3. Innovations in Traditional Chinese Medicine Pills The introduction of modern Western medical knowledge, advancements in pharmaceutical technology, and improvements in formulation processes have led to significant progress and innovation in traditional Chinese medicine dosage forms. For example, during the Republic of China period, pharmaceutical expert Yang Shucheng proposed improvements to traditional pills, first suggesting some process standards for pills: “If there are original soft and moist medicinal materials in the pill, they should be divided into two parts according to the original formula, and boiled into a paste before mixing with other medicines to form pills.” For some potent and bitter medicines that harm the stomach, he proposed using the “mother and child pill method,” which involves making small pills and drying them, then coating them with milder medicines to harmonize the stomach qi. This way, when the pills enter the stomach, the outer layer of harmonizing medicine will dissolve first, gradually exerting its effects, thus both enhancing the medicinal power and reducing damage to the stomach. In his book “Outline of Chinese Pharmaceutical Science,” he detailed the production process of mother and child pills, developing the mother and child pill method. In summary, the Tang and Song dynasties were a peak period for the development of pills, with over 50 types of excipients, some production process requirements proposed, and new types of pills such as wax pills, coated pills, and wax shell pills emerging. The term “pills” began to appear, and the use of pills in clinical practice gradually tended towards chronic diseases. In the Ming dynasty, the use of vermilion coating saw significant development and became widely used, continuing to this day, as seen in formulas like Qizhen pills, Meihua Dian tongue pills, and gynecological regulating pills. The “Bencao Gangmu” lists various types of pills, including large honey pills (Volume 14 Bai Zhu), small honey pills (Volume 34 Ding Xiang), paste pills (Volume 18 Gua Lou), wax pills (Volume 9 Shizhongru), water pills (Volume 48 Han Hao Chong), sugar pills (Volume 17 Bi Ma), medicinal juice pills (Volume 8 Fen Xi), concentrated pills (Volume 35 Zao Jiao), and coated pills (Volume 29 Mi La). Among them, coated pills are further divided based on the coating, such as “Xiong Huang as coating” (Volume 17 Wu Tou), “Luo Qing as coating” (Volume 17 Lang Dang), “Huang Dan as coating” (Volume 17 Chang Shan), “Qing Dai as coating” (Volume 16 Wang Bu Liu Xing), “Bai Cao Shuang as coating” (Volume 39 Mi La), and “Yanzhi as coating” (Volume 14 She Chuang Zi). Of course, these coatings were not entirely created in the Ming dynasty, but their widespread application was adapted to the production situation of medicinal agents at that time. After the founding of New China, due to technological advancements, the machinery for traditional Chinese medicine production has developed significantly, and dosage forms have continuously been reformed, with new types of concentrated pills, drop pills, and micro pills emerging one after another. Due to their simple production methods, small dosages, and good efficacy, they have received attention from all sectors of society and have become one of the preferred dosage forms in the development of new traditional Chinese medicines. In summary, pills originated before the Western Han dynasty, and due to their convenience for storage and use, especially through the gradual increase in pill size to control dosage, pills have been passed down through generations. Initially, most were water pills, but with changes in disease patterns and improvements in manufacturing processes, honey pills appeared during the Han dynasty, and wax pills, coated pills, and wax shell pills emerged during the Sui and Tang dynasties, with the theory of pills further refined. During the Song, Yuan, Ming, and Qing dynasties, the production of pills became more diversified and standardized, and in modern times, the dosage forms and production processes of pills have continuously innovated, making traditional Chinese medicine pills a major dosage form for industrialized mass production of Chinese patent medicines.
Pills
Pills refer to spherical preparations made from finely powdered medicinal materials or extracts combined with suitable binders or excipients. Pills are one of the dosage forms created by the Chinese laboring people in their long struggle against diseases. The earliest medical texts in China, the “Neijing,” already recorded “Four black fish bones and one barley pill.” Early pills developed from decoctions. Later, generations of Chinese medicine practitioners widely applied them in clinical practice, becoming a large dosage form with a wide variety and refined preparation techniques, with increasingly perfected theories.
Classical Chinese medical texts, such as the “Shennong Bencao Jing,” state: “Medicinal properties are suitable for pills,” and the “Yuhang Jing” states: “Pill medicines can dispel wind and cold, break accumulations, and dissolve hard lumps.” The “Su Shen Liang Fang” states: “Highly toxic substances must use pills.” Since the Han and Jin dynasties, it has been proposed that “Pill medicines are treated with gentleness,” and “Pills are slow.” Pills dissolve slowly in the gastrointestinal tract after ingestion, gradually releasing the medicine, and their effects last longer; for toxic, potent, or irritating medicines, they can delay absorption, reducing toxicity and adverse reactions. Therefore, pills are often used in clinical treatment for chronic diseases or for patients with weak constitutions or those needing to harmonize qi and blood after illness.
Pills can accommodate solid and semi-solid medicines, as well as viscous liquid medicines; they can also use coatings to mask unpleasant odors. The production technology and equipment for pills are relatively simple, making them suitable for grassroots medical units to prepare.
However, pills also have certain drawbacks, such as large dosages for some, making it difficult for children to take. The production process is lengthy, with many opportunities for contamination; improper operation can affect disintegration and efficacy. On the other hand, the effective component standards for Chinese patent medicine pills still require further in-depth research.
Pills can be classified into the following categories based on their preparation methods or excipients:
(1) Classification by Preparation Method
Plastic pills: These refer to pills made from a mixture of finely powdered medicinal materials and suitable binders, formed into soft and hard pills, and then divided into pill granules, such as honey pills, paste pills, some concentrated pills, and wax pills.
Water pills: These refer to small spherical pills made from finely powdered medicinal materials using suitable liquids as binders, such as water, honey water, or medicinal juices. They are generally suitable for clearing heat, relieving exterior conditions, and promoting digestion.
Paste pills: These refer to pills made from finely powdered medicinal materials using starch paste or rice paste as binders. They are suitable for containing certain toxic, potent, or irritating medicines, such as Xihuang pills and small gold pills.
Wax pills: These refer to pills made with beeswax as a binder. They are suitable for containing toxic or strongly irritating medicines.
Concentrated pills: These refer to pills made from concentrated decoctions or extracts of some medicinal materials mixed with suitable excipients or finely powdered medicines. They are small in size and convenient for taking.
Other pills: Based on the principles of syndrome differentiation and treatment in traditional Chinese medicine, some other materials (brown sugar, white sugar, syrup, jujube paste, gelatin, animal organs, milk, etc.) are selected as binders for pill making based on clinical treatment needs.
Water Pills
Water pills, also known as water-fanned pills, are small spherical pills made from finely powdered medicinal materials using cold boiled water, medicinal juices, or other liquids as binders.
Water pills developed from decoctions. Initially, they were made by combining a portion of the medicinal decoction with another portion of finely powdered medicinal materials using the dripping method. They gradually evolved to use various water-soluble liquids as binders, employing the fanning method to make small pills from all or part of the powdered medicines. The fanned pills are small, with a dense and smooth surface, making them easy to swallow and less prone to moisture, which is beneficial for storage. During operation, the layering can be adjusted based on the properties and odors of the medicines to mask unpleasant smells and prevent the loss of aromatic components. Since the binders are water-soluble, they disintegrate easily after ingestion, allowing for rapid absorption and effect. The types of excipients used for water pills are diverse, selected according to the disease and the requirements of syndrome differentiation in traditional Chinese medicine to enhance efficacy.
The production equipment for water pills is simple, but the operation is complex. It is also challenging to control the main medicinal content and disintegration rate of the finished product; improper management of the pharmaceutical factory’s equipment and hygiene can lead to microbial contamination; and if the moisture content is not well controlled, it is also prone to mold. These issues urgently need to be addressed.
The specifications for water pills vary in size based on clinical needs, so they can differ. Historically, they have often been referenced against physical objects, such as the size of mustard seeds, wutong seeds, and small red beans, etc. Currently, a unified weight standard is used. The 1985 edition of the Chinese Pharmacopoeia specifies the number of pills per gram for various water pills. For example, the Meihua Dian tongue pills weigh 1 gram for every 10 pills; the Shangqing pills weigh 1 gram for every 20 pills.
(1) Requirements for Medicinal Powder in Water Pills
The fineness of the medicinal materials is crucial for the quality of water-fanned pills. Generally, the medicinal powder for water-fanned pills should pass through a 100-120 mesh sieve. Finely powdered pills yield smooth and round granules. If the medicinal materials are coarsely ground, the resulting granules will have rough surfaces and fibers, making them difficult to form. The powders used for molding or coating should also be selected based on the properties of the medicines in the prescription, ground to a fine powder passing through a 120-140 mesh sieve. Since a prescription often consists of plant, animal, mineral, and synthetically produced medicines, their textures can vary from loose, brittle, sticky, and slippery. For example, Dangshen, Baizhu, Liangjiang, Xiangfu, Licorice, Nanshen, Baizhu, and Shanyao contain high levels of proteins, sugars, starches, and are more absorbent, making them easier to form when using water as a binder. For prescriptions containing mineral substances like magnetite, vermilion, natural copper, and xiong huang, or carbonaceous medicines like Ai Ye Tan, palm charcoal, and Baicao Shuang, if they are present in excess, sticky binders should be selected. Oily seeds or nut medicines are generally coarsely ground, and mixing them with other finely powdered medicines does not hinder the fanning process. However, if there are many oily seeds or nut medicines, it becomes challenging to form pills. Highly viscous medicines containing high sugar content, mucilage, resins, and gels, such as Er Dong, Er Di, Tianma, Huangbai, Baiqi, Gouqi, Wuweizi, Ruxiang, Mo Yao, Ercha, Xuejie, Baijiaoxiang, Suhe oil, Jujube paste, Huangjing, Dahuang, and Aloe, should be specially treated during the prescription to avoid adhesion and difficulty in forming, which would affect the quality of water-fanned pills.
(2) Selection of Common Excipients
The types of excipients used for water pills are numerous, primarily serving to moisten the powdered medicines, enhance their adhesive properties, and increase the solubility of certain effective components in the main medicine; some also have therapeutic effects. Therefore, appropriately selecting excipients is crucial to control disintegration and enhance efficacy. Common excipients for fanned pills include:
1) Water—Water is the most widely used and primary excipient in fanned pills. Although water itself has no adhesive properties, it can moisten and dissolve the mucilage, sugars, starches, and gels in the medicines, producing adhesion after moistening, allowing for fanning into pills. To ensure the quality of the finished product and reduce microbial contamination, freshly boiled and cooled water or distilled water should be used. For prescriptions containing cardiac glycosides, such as digitalis, water should not be used as a wetting agent, as it can gradually decompose the glycosides in the original powder. For prescriptions containing hygroscopic or soluble components, as well as toxic or potent medicines, they should first be dissolved or mixed in a small amount of water to facilitate dispersion before mixing with other medicines for fanning. For clinical treatments where there are no special requirements for excipients, any medicines that do not deteriorate upon contact with water can be used for water-fanned pills, which should be dried immediately after fanning.
2) Wine—Wine has strong penetration, promotes blood circulation, opens meridians, and raises the temperature of medicines, so prescriptions for promoting circulation and activating blood often use wine as a fanning agent. Depending on regional habits and the properties of the medicines in the prescription, yellow wine (with an alcohol content of about 12-15%) and white wine (with an alcohol content of about 50-70%) are commonly used. Different wines contain varying concentrations of ethanol, which can dissolve resins and oily components in the medicinal powders, increasing their adhesive properties. However, the adhesive properties of wine are weaker than those of water, and when water is too strong as a wetting agent, making fanning difficult, wine is often used instead. Additionally, wine is an excellent organic solvent that helps to extract alkaloids, volatile oils, and other effective components from the medicinal powders, enhancing efficacy, and it also has a preservative effect, preventing the medicines from spoiling during the fanning process, making it easier to dry the products.
3) Vinegar—Vinegar can disperse blood stasis, promote blood circulation, and reduce swelling and pain. Prescriptions that enter the liver meridian to disperse blood stasis and relieve pain often use vinegar as a fanning agent. Medicinal vinegar is used as a wetting agent, containing acetic acid (about 3-5%), which has advantages similar to both water and wine, and has the potential to convert alkaloids in the medicinal materials into salts, thereby enhancing the solubility of alkaline components in the medicines and increasing efficacy.
4) Medicinal juices—For certain medicines that are difficult to powder, they can be made into liquids to serve as fanning agents, which not only helps preserve their medicinal properties but also enhances efficacy and facilitates the fanning process. Medicines with the following properties can be used in this way:
① For prescriptions containing fibrous materials (such as Da Fu Pi, Si Gua Luo, Qian Nian Jian), hard minerals (such as magnetite, natural copper), resinous substances (such as Ferula, Ruxiang, Mo Yao), pastes (such as Ercha, Aloe), and soluble salts (such as Mangxiao, Qingyan), their decoction or water can be used as a binding agent.
② For prescriptions containing milk (such as Mai Men Dong pills), cow bile (such as cow bile and bitter ginseng pills), bear bile (such as Meihua Dian tongue pills), and bamboo juice (such as bamboo juice phlegm pills), appropriate amounts of water can be added to dilute them into a suspension for fanning.
③ For prescriptions containing fresh ginger, scallions, or other fresh medicines, to prevent the effective components from being destroyed by heat, the fresh medicines can be crushed and juiced to serve as a binding agent for fanning.
Honey Pills
Honey pills are solid medicinal preparations made by using refined honey as a binder for finely powdered medicines. Honey pills are the most widely used type of traditional Chinese medicine in clinical practice. Due to the rich nutritional components in honey, they have a nourishing effect; their sweetness can mask unpleasant tastes; and they have effects such as moistening the lungs, relieving cough, promoting bowel movements, and detoxifying. All of these align with the traditional Chinese medical principle that “insufficient essence should be supplemented with flavor” and “eliminating various diseases and harmonizing all medicines.” Honey also contains a large amount of reducing sugars, which can prevent the oxidation and deterioration of the effective components in medicinal materials; after refining, honey has strong adhesive properties, and when mixed with powdered medicines, the surface of the pill does not harden easily, maintaining a high degree of plasticity. The resulting pills are round, smooth, and moist, with low moisture content, slow disintegration, and long-lasting effects, making it an excellent binder. Honey pills are commonly used for treating chronic diseases and those requiring nourishment.
However, due to the large amount of honey used in honey pills, improper preparation techniques can lead to moisture absorption and spoilage, prompting some varieties to be reformulated as water honey pills or other dosage forms.
Water honey pills and concentrated pills:
Water honey pills:
Water honey pills are small spherical dried pills made from finely powdered medicinal materials using honey water as a binder.
Water honey pills were created by pharmaceutical workers after the liberation based on the principles of water-fanned pills. This method is simpler than manual molding, has higher production efficiency, and results in smaller, smoother, and rounder pills that are easy to swallow. This method uses honey, rich in nutrients, combined with water to create a binder, saving honey, reducing costs, and facilitating storage. Therefore, many nourishing medicines are made into small honey pills using honey water as a binder. Currently, this method is widely used, especially in southern provinces with humid climates, where more water honey pills are produced.
The properties of the medicinal powder and the ratio of honey water are closely related. The concentration of honey water used for fanning must be suitable for the properties of the medicinal powder to produce qualified water honey pills. Generally, for moderately characterized medicinal powders, 30g of refined honey is used for every 100g of powdered medicine, with water added in a 1:3 ratio. After refining the honey, three times the amount of water is added, mixed, boiled, and filtered. However, for powdered medicines with high sugar content, mucilage, or gel-like properties, a lower concentration of honey water should be used, such as 10-15g of refined honey for every 100g of powdered medicine, mixed with an appropriate amount of water, stirred, boiled, and filtered to create a binding agent. For powdered medicines with high fiber and mineral content, 40-50g of refined honey should be used for every 100g of powdered medicine, mixed with an appropriate amount of water, stirred, boiled, and filtered to create a binding agent, with the proportions of honey water and powdered medicine being similar to those for water-fanned pills.
Concentrated Pills:
Concentrated pills refer to pills made from concentrated extracts of some medicinal materials mixed with suitable excipients or finely powdered medicines. They are also known as “medicinal paste pills.” It is generally believed that concentrated pills are an improved dosage form of pills. In fact, as early as the Jin dynasty, Ge Hong’s “Emergency Prescriptions for the Afterlife” recorded: “…remove the dregs, boil the soup, and make it into pills…” The ancient “Jian Gao Wan” and modern concentrated pills are similar in preparation methods and principles of processing medicinal materials. The latter has improved certain operational processes, expanded its applicability, and reformulated other types of pills, such as water pills and honey pills, into concentrated pills. Concentrated pills are one of the better types of pills, characterized by a significant reduction in size compared to traditional honey pills and water pills. For example, the Baohua pill is prescribed at 6g for water pills, while the concentrated pill is only 3g, equivalent to the efficacy of 6g of water pills, with a dosage that is half that of water pills. Similarly, the Liuwei Dihuang pill is prescribed at 9g for large honey pills, containing 4.5g of raw medicine, while the concentrated pill is only 2.6g, a quarter of the honey pill dosage. The smaller dosage is easier to take, increases efficacy, and is more convenient for carrying and transportation, saving a significant amount of excipients, thus aligning with the characteristics of traditional Chinese medicine while being suitable for mechanized production and grassroots units. However, during the boiling or processing of medicinal materials, improper handling or poor powdering techniques can damage some effective components and affect disintegration, thereby reducing efficacy. Concentrated pills can be divided into water pill-type concentrated pills and honey pill-type concentrated pills based on their excipients.
Paste Pills
Paste pills are small pills made from finely powdered medicinal materials using rice paste or flour paste as a binder. Paste pills have a long history, first appearing in the Han dynasty’s “Treatise on Febrile Diseases” and widely used in the Song dynasty. After drying, paste pills become relatively hard, disintegrating slowly in the stomach, allowing for gradual release of the medicine and prolonging its effects while reducing irritation to the gastrointestinal tract. The “Tang Liquid Bencao: Examples of Using Pills and Powders” states: “The pills… are made from thick flour paste, taking their time to dissolve.” Therefore, prescriptions containing highly toxic or strongly irritating medicines (such as Ba Dou, Ma Qian Zi, Sheng Ban Xia, Mu Bie Zi, Dan Yao, etc.) are often made into paste pills to achieve a slow-release effect. Due to the different types of paste powders and preparation methods used, the adhesive properties and clinical therapeutic effects of the resulting paste pills can vary, thus paste pills also have a certain degree of flexibility, adapting to the characteristics of various prescriptions to fully exert the therapeutic effects of the medicines. However, if the paste powder is improperly selected or the preparation techniques are poor, the resulting pills often exhibit inadequate disintegration and spoilage.
Wax Pills
Wax pills are round pills made from medicinal powders using beeswax as a binder. In the Jin dynasty, Li Gao stated, “Wax pills are difficult to dissolve and take effect slowly, or they do not harm the spleen and stomach when using toxic medicines.” Because the main component of beeswax, fatty acid beeswax, has low polarity and is insoluble in water, pills made from it release their medicines very slowly in the body, prolonging their effects. By adjusting the amount of wax, pills can be made to remain inactive in the stomach while taking effect in the intestines, thus preventing poisoning or strong stimulation to the stomach from the medicines. Therefore, wax pills are often the first choice for oral preparations containing many toxic and strongly irritating medicines. Traditional wax pills include Sanhuang Baoluo pills, millet inch gold pills, and Zhi Lou Wushuang pills, among others. In preparation, the wax must be refined before being added to the medicines, removing impurities (refining wax can be done by bleaching or boiling). The refined wax is then heated and melted, and when slightly cooled (around 60°C), the edges begin to solidify, and when a membrane appears on the surface, the medicinal powder is added and quickly stirred to mix evenly, then rolled into pills. The key to operation is to control the temperature, mixing the medicines while warm and rolling quickly (to maintain the temperature of the mixture around 60°C). If the temperature is too high, the mixture becomes soft and difficult to shape; if too low, it becomes hard and difficult to roll. Some wax pills can also be sealed with wax paper and then stamped with the product name. Wax paper pills are made from a mixture of beeswax and white wax (Chuan Bai Zhan) to form a wax shell, wrapping the pills inside. Pills sealed with wax paper are mostly honey pills, with a small number being wax pills, and the prescriptions often contain aromatic and volatile medicines. The purpose is to prevent the medicines from coming into contact with air, becoming contaminated, spoiled, or undergoing physical and chemical reactions, preventing the loss of aromatic and volatile components, and maintaining a certain moisture content in the pills to keep their hardness and softness consistent. The preparation of wax shells, also known as “hanging wax paper,” is relatively complex. The size of the wax shell is made according to the size of the pills, divided into five specifications, using a wooden ball of a certain specification as a mold, dipping it in wax liquid, and allowing it to solidify. The materials for making wax shells must be pure; impurities can cause the finished product to crack or deform. The refining of beeswax, in addition to the methods mentioned above, also requires sun-waxing to remove color. The mixing wax’s temperature should be between 55°C and 59°C, with a ratio of 40% beeswax to 60% white wax; too much white wax makes it brittle, while too little makes it soft, and adjustments can be made according to seasonal changes. Before dipping the wax, the wooden balls should be boiled thoroughly to increase their specific gravity, making them easier to dip in wax; the surface of the boiled wooden balls should be slightly moist, making it easier to peel off the wax shell. The temperature of the wax liquid for dipping should be controlled between 70°C and 74°C; if too high, the wax shell becomes thin and deforms, while if too low, it becomes thick and wastes material. The room temperature should be maintained between 18°C and 25°C, ensuring that the surface of the wax liquid does not form a membrane. The finished wax shell is filled with pills and sealed, with the temperature of the wax liquid for sealing kept between 75°C and 77°C; if too low, it forms two layers of wax paper or easily peels off and cracks, while if too high, the surface becomes uneven. The surface of the sealed wax paper pills is stamped with a cow horn stamp heated over an alcohol lamp, and then coated with gold, silver, or red powder, completing the product. Traditional wax paper pills include Dahuoluo Dan, Wujiao Baifeng Wan, Suhe Xiang Wan, Ren Shen Zai Zao Wan, An Gong Niu Huang Wan, Niu Huang Qing Xin Wan, Toubone Zhen Feng Dan, An Shen Zhan Yu Wan, and Sanhuang Baoluo Wan, among others. For example, the prescription from the Qing dynasty’s Wu Qian in the “Yizong Jinjian” Volume 75 states: “Take 90g of Tianzhu Huang, 45g of Danggui, 90g of Liu Jinu, 90g of Hongya Dajie (vinegar roasted), 120g of Tenghuang (tofu made), 90g of Ercha, 9g of Ruxiang (vinegar roasted), 9g of Shexiang, 90g of Xuejie, 9g of Mercury (roasted), 9g of Black Lead, 6g of Amber, 90g of Xiong Huang, totaling 777g. Preparation: 1. Grind the vermilion into a fine powder, and separately grind the xiong huang, amber, and musk into fine powders and sieve them. Heat the black lead in an iron pot until melted, then pour in the mercury, stirring constantly until it forms a sandy texture, then remove and let cool. Mix the remaining nine ingredients with the prepared mercury and black lead, grind into a fine powder, and combine with honey to form pills as large as wutong seeds. Packaging: Wax paper or wax tubes for sealing, stored in a cool, dry place. Function: Detoxification and blood stasis removal. Indications: Trauma injuries, blood stasis obstruction. For external application, mix with sesame oil and apply to the affected area. Dosage: For internal use, take one pill, once or twice a day, with warm wine. For external use, mix with a little sesame oil and apply to the affected area. Or follow the doctor’s advice for use. Contraindications: Pregnant women should avoid use. Avoid eating raw and cold foods.
Preparation Methods for Pills
The preparation of pills involves several steps, including refining honey, combining with medicines, forming strips, making pills, packaging, and storage. The selection and refining of honey are key to ensuring the quality of honey pills. Generally, honey that is milky white and light yellow, sweet and fragrant, free of impurities, thick like congealed fat, and low in moisture is preferred. However, due to variations in source, region, and climate, the quality can vary. Honey produced in the north generally has lower moisture content, with Jing Tiao honey and jujube flower honey being the best, while honey produced in the south generally has higher moisture content. The purpose of refining honey is to remove impurities, destroy enzymes, kill microorganisms, evaporate moisture, and enhance viscosity. The methods include using a copper pot or direct fire for small-scale production, or using steam jacketed pots or vacuum evaporators for large-scale production, followed by filtering out impurities. The degree of refining honey is divided into tender honey, refined honey, and old honey. Tender honey is heated to boiling, reaching temperatures of 110-114 degrees, with a color change and a sticky texture, losing about 3% of its moisture. It is suitable for prescriptions containing high levels of fat, starch, mucilage, sugars, and animal tissues. Refined honey is further heated to temperatures of 110-116 degrees, producing light red, glossy bubbles, with strong stickiness but no white threads, losing about 13% of its moisture, suitable for prescriptions containing fibrous, starchy, sugary, and some oily ingredients. Old honey is heated to temperatures of 118-122 degrees, with a moisture content below 10%, a relative density of about 1.40, producing large, glossy bubbles, and very sticky when pinched, forming long white threads when fingers are pulled apart, and forming beads when dropped in water. Old honey has strong adhesive properties, suitable for making pills from materials with poor adhesion, otherwise, the surface of the pills will be rough and not moist.
Storage Methods Honey pills and drop pills must be stored tightly and kept in a cool, dry place. The storage time for honey pills is best not to exceed one year. Paste pills are most prone to insect infestation and should be stored in a dry place, checked every month or two. The storage method for water pills is basically the same as for paste pills. In particular, pills containing aromatic medicines must be tightly sealed and protected from heat, with a storage time of no more than one year. Wax pills, due to their excellent packaging, are not prone to spoilage and can be stored in a cool place. Concentrated pills are often packaged in bottles or plastic bags, and their storage and maintenance can refer to those for water pills and honey pills, but due to their strong hygroscopicity, they are more prone to mold and insect infestation, requiring careful sealing and moisture-proofing.
Dosage Methods Generally, pills should be taken under the guidance of a physician. The dosage of pills is generally small, and blind high-dose use should be avoided, as it can hinder the stomach and spleen, leading to adverse consequences. Swallowing method: Most patients take traditional Chinese medicine pills with warm water. Large honey pills cannot be swallowed whole due to their size, so they are often chewed or broken into smaller pieces before being taken with warm water. Although the swallowing method is convenient, the medicines are not easily digested and absorbed, especially for patients with stomach issues who feel uncomfortable after taking the medicine. Medicinal drink method: Sometimes, to enhance the therapeutic effects of traditional Chinese medicine, doctors may instruct patients to take the medicine with medicinal drinks. For example, when using Huoxiang Zhengqi pills or Fuzhong Li pills to treat stomach pain or vomiting, fresh ginger decoction can be used for administration. Boiling pills method: First, the pills are crushed with an appropriate amount of warm water to form a paste, and then the soup is taken with the residue. This method helps to release and absorb the effective components of the medicines, especially suitable for patients with poor gastrointestinal digestion and absorption.
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