Information of commonly used excipients for tablets

Generally speaking, tablets are composed of two kinds of substances, one is the drug that plays a therapeutic role (i.e the main drug), the other is some substances without physiological activity Their functions mainly include: filling, adhesion, disintegration and lubrication, and sometimes, coloring, flavor correction and aesthetics These substances are collectively called excipients or adjuvants According to their different functions, excipients are often divided into four categories （1） Diluent (diluents) The main function of diluent (or fil1ers) is to fill the weight or volume of tablet, so as to facilitate tablet pressing; commonly used fillers include starch, sugar, cellulose, inorganic salt, etc.; determined by tablet pressing process, preparation equipment and other factors, the diameter of tablet can not be less than 6mm, and the weight of tablet is more than 100mg, if the main drug in tablet is only a few milligrams When grams or tens of milligrams are added, the tablet cannot be made without proper fillers Therefore, the diluent plays an important role in increasing its volume and helping its formation 1 Corn starch is commonly used as starch It is very stable in nature, does not work with most drugs, and its price is relatively cheap It has small hygroscopicity and good appearance and color In actual production, it is often mixed with sugar powder and dextrin with good compressibility This is because the compressibility of starch is poor If it is used alone, the extruded tablets will be too loose 2 sugar powder Sugar powder refers to the white powder made of crystalline sucrose after being dried and crushed at low temperature It has the advantages of strong adhesion, can be used to increase the hardness of the tablet, and make the surface of the tablet smooth and beautiful Its disadvantages lie in the strong hygroscopicity, long-term storage, which will make the hardness of the tablet too large, and it is difficult to disintegrate or dissolve Except for buccal tablets or soluble tablets, it is generally not used alone, often with dextrin Starch 3 Dextrin is the general name of the intermediate product of starch hydrolysis Its chemical formula is (C6H10O5) n · xH2O, and its water-soluble substance is about 80% It dissolves slowly in cold water, is easy to dissolve in hot water, and is insoluble in ethanol It is also known as high viscosity dextrin (high viscosity dextrin), which has strong cohesiveness Improper use will cause one-sided pockmarks, watermarks or tablets to disintegrate or dissolve slowly Similarly, if not fully crushed and extracted in content determination, it will affect the accuracy and reproducibility of the determination results Therefore, dextrin is rarely used alone and in large quantities as a filler, often with sugar powder Starch is used together 4 Lactose lactose is an excellent tablet filling agent, which is extracted from whey It is widely used in foreign countries, but not in China because of its high price Commonly used crystalline lactose containing one molecule of water, that is, alpha lactose, has no hygroscopicity, good compressible property, stable nature, no chemical reaction with most drugs, and the tablets are smooth and beautiful The lactose obtained by spray drying is crystallized lactose, and its fluidity and compressible property are good, which can be used for direct compression of powder 5 Compressible starch, also known as pregelatinized starch, is a new type of pharmaceutical excipient It has been published in British, American, Japanese and Chinese Pharmacopoeia It was successfully developed in 1988 in China and has been widely supplied to the market Domestic compressible starch is a part of pre gelatinized product (full pre gelatinized starch is also called α - starch), which is equivalent to starch rx1500 of foreign Colorcon company This product is a multi-functional auxiliary material, can be used as a filler, with good fluidity, compressibility, self lubrication and dry adhesion, and has a better disintegrating effect If it is used for direct compression of powder, the dosage of magnesium stearate shall not exceed 0.5% to avoid softening effect 6 Microcrystalline cellulose microcrystalline cellulose (MCC) is a kind of crystalline cellulose with small degree of polymerization, which is produced by partial hydrolysis of cellulose MCC has good compressibility, strong binding force, and the pressed tablet has great hardness It can be used as a "dry adhesive" for direct compression of powder The commodity name of foreign products is Avicel, and there are several specifications according to the particle size Domestic microcrystalline cellulose has been widely used in China, but its quality needs to be further improved, and its product types need to be enriched In addition, the tablets containing 20% microcrystalline cellulose had better disintegration 7 Inorganic salts are mainly some inorganic calcium salts, such as calcium sulfate, calcium hydrophosphate and medicinal calcium carbonate (produced by sedimentation method, also known as sedimentation calcium carbonate), etc Among them, calcium sulfate is more commonly used, which is stable in nature, odorless and tasteless, slightly soluble in water, and compatible with a variety of drugs The tablet made of calcium sulfate has a bright and clean appearance, good hardness and disintegration, and has no adsorption effect on drugs Calcium sulfate dihydrate is often used in tablet excipients However, it should be noted that calcium sulfate interferes with the absorption of some main drugs (tetracycline drugs), which should not be used at this time 8 Mannitol and mannitol are in the form of granule or powder When they are dissolved in the mouth, they absorb heat, so they have a sense of cooling At the same time, they have a certain sweetness, and there is no sense of gravel in the mouth Therefore, they are more suitable for preparing chewing tablets, but the price is a little expensive They are often used in combination with sucrose （2） Adhesives some drug powders have viscosity Only adding proper liquid can induce their inherent viscosity At this time, the added liquid is called moistening agent Some pharmaceutical powders do not have viscosity or have less viscosity, so it is necessary to add some viscous substances such as starch slurry to make them stick together At this time, the added viscous substances are called adhesives Because the main function they play is actually to combine the drug powder, the above wetting agent and adhesive can also be collectively called adhesive 1 Distilled water is a kind of wetting agent In application, water is often absorbed quickly by materials Therefore, the phenomenon of uneven wetting is easy to occur Zui should use low concentration of starch or ethanol instead to overcome the above shortcomings 2 Ethanol is also a wetting agent It can be used for drugs that are easy to decompose when encountering water, or drugs that are too sticky when encountering water With the increase of ethanol concentration, the viscosity produced after wetting decreases Therefore, the alcohol concentration depends on the properties of raw and auxiliary materials, generally 30% - 70% Ethanol is often used as a wetting agent in traditional Chinese medicine extract tablets, but it should be operated quickly to avoid strong sticky lumps caused by ethanol volatilization 3 Starch starch starch slurry is the common adhesive for Zui in tablets, with the concentration of 8% - 15%, and the concentration of 10% starch starch slurry Zui as the common one; if the material has poor compressibility, the concentration of starch slurry can be increased to 20%, on the contrary, the concentration of starch slurry can also be reduced properly, for example, aluminum hydroxide tablets use 5% starch slurry as the adhesive There are two main methods of starch pulping, boiling and washing, which make use of the property that starch can gelatinize Gelatinization refers to the phenomenon that starch forms uniform paste after being heated (the temperature of corn starch gelatinization is 77 ℃) After gelatinization, the viscosity of starch increases sharply, so it can be used as the adhesive of tablets Specifically, starch is suspended in a small amount (1-1.5 times) of water, then poured into a certain amount of boiling water according to the concentration requirements, and continuously stirred and gelatinized; boiling is to suspend starch in the whole amount of water, and then heated and continuously stirred in a sandwich vessel (it is not suitable to use direct fire heating to avoid coking), until gelatinization Because starch is cheap and easy to get and has good adhesiveness, most starch paste is used as the adhesive when it can make granules and meet the requirements of tablet pressing 4 Carboxymethylcellulose sodium carboxymethylcellulose sodium (CMC Na) is a carboxymethyletherate of cellulose, insoluble in ethanol, chloroform and other organic soluble coal; when dissolved in water, the surface of Zui primary particles expands, and then the water slowly penetrates into the interior to form a transparent solution, but it takes a long time Zui is better to heat it to The dissolution process can be greatly accelerated at 60 ℃ ~ 70 ℃ The concentration used as adhesive is generally 1% - 2%, and it has strong viscosity It is often used in drugs with poor compressibility However, it should be noted whether the hardness of tablets is too large or disintegration is beyond the limit 5 Hydroxypropyl cellulose Hydroxypropylcellulose (HPC) is a kind of hydroxypropyl etherification of cellulose It contains 53.4% ～ 77.5% of hydroxypropyl (the low substitute whose hydroxypropyl content is just 7% ～ 19% is called low substituted hydroxypropyl cellulose, i.e L-HPC, which is a disintegrant) It is white powder and easy to dissolve in cold water When heated to 50 ℃, it will gelatinize or swell In propanol and propylene glycol This product can be used not only as the adhesive for wet granulation, but also as the adhesive for direct compression of powder 6 Methylcellulose, ethylcellulose, methylcellulose and ethylcellulose (MC, EC) are the etherification of methyl or ethyl cellulose, containing 26.0% - 33.0% methoxy or 44.0% - 51.0% ethoxy Among them, methylcellulose has good water solubility, which can form viscous colloidal solution and be used as adhesive However, it should be noted that when sucrose or electrolyte reaches a certain concentration, the product will precipitate Ethyl cellulose is insoluble in water and has high solubility in ethanol and other organic solvents It can produce viscosity of different strength according to its concentration Its ethanol solution can be used as the adhesive of water sensitive drugs However, it should be noted that the product has strong viscosity and is insoluble in gastrointestinal fluid, which will block the disintegration of tablets and drug release At present, this characteristic of ethyl cellulose is often used in slow and controlled release preparations (skeleton or membrane controlled release) 7 Hydroxypropylmethylcellulose (HPMC) is a kind of film coating material commonly used by Zui Because it dissolves in cold water and becomes a viscous solution, it is also commonly used as an adhesive in 2% - 5% solution In the preparation of HPMC aqueous solution, Zui first added HPMC to 1 / 5-1 / 3 of the total volume of hot water (80 ℃ ~ 90 ℃), fully dispersed and hydrated, and then stirred continuously under cooling conditions, adding cold water to the total volume The product is insoluble in ethanol, ether and chloroform, but soluble in 10% - 80% ethanol solution or mixture of methanol and dichloromethane 8 Other binders, 5% - 20% gelatin solution, 50% - 70% sucrose solution, 3% - 5% PVP aqueous solution or alcohol solution, can be used for those drugs with poor compressibility However, it should be noted that these binders are very viscous and the tablets made are relatively hard, and a little excess will cause the collapse of the tablets beyond the limit （3） Disintegrants disintegrants are substances that make tablets break into small particles in gastrointestinal fluid rapidly Apart from slow (controlled) release tablets and some special-purpose tablets, disintegrants should be added to general tablets Because of their strong water absorption and expansion, they can break up the binding force of tablets, make tablets break up from a whole sheet into many small particles, and realize the disintegration of tablets, so it is very conducive to the dissolution and absorption of the main drugs in tablets 1 Dry starch is a kind of Zui, which is a classic disintegrating agent It has a water content of less than 8%, strong water absorption and certain expansibility It is more suitable for tablets of water-insoluble or slightly soluble drugs, but it has a poor disintegrating effect on soluble drugs, because the concentration of soluble drugs is poor when they are dissolved in water,