Pharmaceutical excipient
A pharmaceutical excipient , including pharmaceutical carrier called, is a substance that in addition to the drug in the manufacture of medicaments is used. Optimally, auxiliary substances are pharmacologically and toxicologically inert, they have the following functions:
- Shaping: Auxiliaries carry the drug and give the drug its shape
- Manufacturability: Auxiliaries enable or improve certain manufacturing steps in drug manufacture
- Control of the release of active ingredients: Auxiliaries control the release of active ingredients in a targeted manner or transport them to their target site
- Improvement of stability: auxiliaries ensure a sufficient shelf life of a drug
Pharmaceutical additives can also be used to adjust drug properties such as color, smell, taste and physiological tolerance. So-called adjuvants are used as active enhancers, especially in vaccine production.
In addition, as in the case of active ingredient-free, dermatological bases, auxiliary substances can achieve a healing effect through physical effects. These preparations are then referred to as medical devices.
Pharmaceutical excipients must be of consistent and appropriately pure quality. Many, like medicinal substances, are characterized and specified in the pharmacopoeia . They should be physiologically well tolerated and, apart from their intended function, as inert as possible . Exceptions are auxiliary materials, which are referred to as bases or basic materials. They give the preparation characteristic properties. These include, for example, Vaseline, which is often used as an ointment base, or hard fat, which is often used to make suppositories. Some auxiliary materials are only required to carry out certain manufacturing steps and are then removed (e.g. water, organic solvents ). In all EU countries, it applies to finished medicinal products that the pharmaceutical excipients they contain must be declared in the information for healthcare professionals and the package insert .
| Examples of pharmaceutical excipients by function and use | ||
|---|---|---|
| function | Sample (s) of substance, use in product or process | |
| Filler, foundation | Lactose , cellulose , starches , sucrose (tablets); Paraffin (ointments); Hard fat (suppositories); Polyethylene glycols (Macrogols, PEG), polyethylene oxides (PEO) (tablets, ointments, creams) | |
| Solvents , humectants | Water , ethanol , isopropanol (granulation, film spraying) | |
| Emulsifiers | Cetyl stearyl alcohol , glycerol monostearate, lecithin , fatty acid esters of sorbitan, polyoxyethylene sorbitan ( polysorbate ), polyoxyethylene, polyoxyethylene fatty alcohol ether (emulsions, creams) | |
| Solubilizers , wetting agents | Polyethylene glycols (PEG, Macrogole), polyethylene oxides (PEO, PolyOx), polysorbates (solutions, suspensions) | |
| buffer | Sodium dihydrogen phosphate , sodium hydrogen carbonate , calcium hydrogen phosphate , trometamol (solutions, creams) | |
| Thickeners and binders | Starches, guar , xanthan , alginate , carrageenan , pectin , tragacanth , polyacrylic acids , polyvinylpyrrolidone (granules, tablets); fumed silica , substituted cellulose ethers ( methylcellulose , ethylcellulose , hydroxypropylcellulose , hydroxypropyl methylcellulose , carboxymethylcellulose ) (tablets, gels, viscous solutions) | |
| Wrapping agents | Sucrose (sugar coating); Gelatin (capsules); Gelatine poly succinate ("soft capsules"), polyacrylates , ethyl cellulose, methyl cellulose (film coating: film capsules, film tablets, pellets) | |
| Decay accelerator, disintegrant | Starches (tablets, tabs); Croscarmellose (tablets, capsules, granules); Sodium hydrogen carbonate in combination with citric acid ( effervescent tablets ) | |
| Glidants and lubricants, mold release agents | Polyethylene glycols (PEG, Macrogole), polyethylene oxide (PEO), talc , magnesium stearate (tableting) | |
| Flow regulators | Highly dispersed silicon dioxide (powder, granules) | |
| Antioxidants | Butylhydroxytoluene , all- rac -α- tocopherol | |
| Preservatives | PHB esters (parabens), benzalkonium chloride , benzyl alcohol , thiomersal | |
| Sweeteners , flavor correctors | Sucrose , sorbitol , sweeteners such as saccharin- sodium and cyclamate ; Flavors | |
| Absorption accelerator | Dimethyl sulfoxide (in topical formulations) | |
Oral dosage forms
Capsules
Various auxiliaries are required for the production of capsules. A distinction is made between capsules, including hard and soft capsules.
Capsule shell
In most cases, the shell of capsules is made of gelatin, as it is well tolerated by the human body. But there can also be other auxiliaries such. B. Hydroxypropylmethylcellulose (hard capsules) or microcrystalline cellulose (soft capsules) can be used for the production of the capsule shell. Hard and soft capsules differ mainly in their composition. The gelatine shell of hard capsules consists of approx. 85% gelatine, 14% water and 1% dye. The shell can also be made from 94% HPMC, 5% water and 1% dye. In the case of soft capsules, a plasticizer is also added to the mass. A possible composition here would be 67% gelatin, 25% plasticizer, 7% water and 1% color.
| Capsule shell | |
|---|---|
| Film maker | Gelatine, HPMC, starch, carrageenan, PVA copolymers |
| Plasticizers | Glycerol, sorbitol |
| Surface active substances | Sodium lauryl sulfate |
| Pigments | Titanium dioxide, iron oxide |
| Dyes | Natural dyes, azo and xanthene compounds |
| Preservatives | p-hydroxybenzoic acid ester |
| Taste corrections | Ethyl vanillin |
Capsule filling
Here, too, there is a difference between hard and soft capsules. Hard capsules can usually only be filled with dry, non-hygroscopic substances. A powder mixture of mannitol (95.5%) and pyrogenic silica (0.5%) is preferably used here. For soft capsules, people like to work with polyethylene glycols and fatty oils as fillers.
| Capsule contents | |
|---|---|
| lubricant | Sodium lauryl sulfate |
| Decay accelerator | Starch derivatives, microcrystalline cellulose |
| Flow regulator | Aerosil |
Tablets
The range of excipients required for tableting is large. A strict classification into groups is not easily possible here, since individual substances can have several functions here. Whether and which auxiliary materials are used in individual cases must first be checked in detail. The tablet base is divided into an inner and an outer phase. The inner phase is made up of the active ingredient (s) and auxiliary materials such as binders, disintegration regulators and fillers. The outer phase consists of flow regulators, lubricants and (mold) release agents.
Inner phase auxiliaries
binder
Binders are decisive for the strength of a tablet. They ensure the cohesion of the powder particles z. B. in a granulate. The more solid a tablet, the worse it will disintegrate. Therefore, the smallest possible amount of binder should be used. Dry binders are used in direct compression. They can be broken down into three categories. As the first natural dry binding agent, this mainly includes microcrystalline cellulose and cellulose powder. Modified and pretreated starches such as B. pregelatinized starches and hydrolyzed starches can be used. The second is inorganic calcium compounds and the third is synthetic polymers. Binding agents such as gelatine, starch paste, gum arabic or tragacanth, as well as synthetic polymers are used in pelletizing.
| binder | |
|---|---|
| Dry binder | Celluloses, starch, hexites, dextrose, lactose, inorganic calcium compounds, synthetic polymers |
| Binding agent pelletizing | Gelatine, starch paste, gum arabic, tragacanth, synthetic polymers |
Filler
In the production of tablets with very small amounts of active ingredient, fillers are used in order to ensure the size or mass of the tablet required for production. Different starches (corn starch, potato starch, wheat starch) are popular because they also act as disintegrants. Lactose, microcrystalline cellulose, glucose, mannitol and sorbitol are also frequently used. It is important that the substances are easily digestible in addition to the requirements mentioned above.
Disintegrants / disintegrants
Tablets are required to disintegrate quickly in most cases. To achieve this, disintegrants or disintegrants are often used. These can be divided into three groups:
1. Substances that increase the capillarity 2. Substances that react when exposed to moisture and effervesce with evolution of gas 3. Substances that increase the wettability of the tablet
| Disintegrants / disintegrants |
|---|
| Starch, celluloses, super disintegrants (sodium starch glycolate, croscarmellose, crospovidone), alginic acid |
External phase auxiliaries
Flow regulators
These auxiliaries ensure an improvement in the flow properties during pressing and dosing. They reduce the friction between the powder particles so that the product can flow better into the die.
| Flow regulators |
|---|
| Metal stearates, Aerosil (0.05-0.5%), fatty acids, waxes, fatty alcohols |
Mold release agent
These auxiliaries prevent the tablet mass to be compressed from sticking to the punch of the tablet machine. Talc or magnesium stearates are often used here.
lubricant
They ensure that the release of the tablet from the matrix is improved. Magnesium stearate and talc are also used here.
See also
Individual evidence
- ↑ S. Ebel and HJ Roth (Eds.): Lexikon der Pharmazie , Georg Thieme Verlag, 1987, p. 318, ISBN 3-13-672201-9 .
swell
- Alfred Fahr , Voigt Pharmazeutische Technologie , Deutscher Apothekerverlag, Edition 12 , ISBN 978-3-7692-6194-3 , Chapter 5 Basic and auxiliary materials in drug formulation pp. 133–196 and Chapter 9 Tablets pp. 278 – S. 302