Application in the pharmaceutical excipient industry

By utilizing the excellent solubility, solubilization, physiological compatibility, bonding ability, and chelating ability of PVP, it can be used as an adhesive, excipient, coating agent, disintegrant, cosolvent, bactericidal disinfectant, solubilizer, sustained-release agent, capsule shell, dispersion stabilizer, film-forming agent, etc. in the field of medicine, medical and health. In some developed countries, such as the United States, Germany, Japan, etc., the application of PVP in the medical and health fields accounts for about 40% -55% of the total PVP consumption. Currently, PVP is used in medicine and healthcare.

The dosage and function in the field of health are shown in the following table：

Application of PVP as a drug excipient

PVP has excellent adhesion performance and strong solubility. The tablets formed by PVP quickly dissolve in the digestive tract after consumption, causing the tablets to expand and disintegrate locally, releasing drug fragments and accelerating the dissolution and absorption of the drug, thus playing a role in rapidly exerting its therapeutic effect. PVP is soluble in water and most organic solvents. Due to these reasons, PVP has been widely used in pharmaceutical tablets, especially abroad. Common drugs that use PVP for tablet bonding are as follows:

Taking compound sulfamethoxazole, aspirin, compound aspirin, paracetamol, vitamin C, persantine, tetracycline, clonidine, benzenesulfonamide, compound analgesics, and chewable tablets as examples, the formula is as follows:

Aluminum hydroxide dry adhesive 0.4g

Magnesium hydroxide fine powder 0.08g

Sugar powder 0.02g

Mannitol fine powder 0.2g

10% PVP ethanol (50%) solution 0.03g

Magnesium stearate 0.015g

Mint oil 0.0005g

The main PVP used as a drug tablet adhesive is PVP-K30, and its dosage depends on the mechanical strength requirements of the drug tablet and the properties of the drug itself, generally ranging from 0.5% to 5%.

Another important use of PVP as a drug excipient is as a co precipitant. Some drugs have good efficacy, but their fatal disadvantage is their low solubility in water, which greatly reduces their bioavailability. The use of certain water-soluble substances to co precipitate with these drugs can improve their solubility and dissolution rate, achieving the effect of reducing dosage and improving efficacy. As a co precipitant for insoluble drugs, PVP is widely used.

The main reason why PVP is used as a drug co precipitant is that the carbonyl O in PVP molecules can bind with the active hydrogen bonds in insoluble drug molecules. On the one hand, it makes relatively small drug molecules amorphous and enter PVP macromolecules. On the other hand, hydrogen bonds do not change the water solubility of PVP. Therefore, the result is that insoluble drug molecules are dispersed in PVP macromolecules through hydrogen bonds, making them easily soluble. The solubility changes of some insoluble drugs after forming co precipitates with PVP are as follows:

The ratio of drug name to PVP co precipitate and the fold increase in solubility

Phenytoin 1:5 2.3

Amorine 1:5 38

Liriopine (297-420um) 1:3 15

The increase in solubility of insoluble drugs in the human body also correspondingly enhances their bioavailability. For example, the bioavailability of phenytoin co precipitated with PVP increased by 1.55 times. The increase in solubility of insoluble drugs after co precipitation is related to the molecular weight and dosage of PVP. Under the same dosage (quality) of PVP, the increase in drug solubility decreases in the order of PVP-K15>PVPK30>PVPK90. This is because the solubilization effect of PVP itself changes in the order of PVP-K15>PVPK30>PVPK90. Generally, PVP-K15 is used more frequently.

The increase in solubility of co precipitates of insoluble drugs and PVP varies complexly with the amount of PVP used. For a certain molecular weight of PVP, the number of drug molecules that each PVP molecule can bind to is constant. Insoluble drugs often have a certain crystalline state. When the amount of PVP used is not sufficient to bind a certain amount of drug and make it in an amorphous dispersed state, the drug still remains in a crystalline state with little change in solubility. PVP must reach a certain content in order for the drug to appear as an amorphous dispersed system, and its solubility can be significantly increased in order to achieve rapid dissolution and absorption. However, different drugs have different levels of amorphous dispersed PVP content when co precipitated with PVP. For example, the value of cyclohexylamine acetate is 70%. Other drugs that can increase solubility and bioavailability in the human body through PVP co precipitation include beta carotene, chloramphenicol, dexamethasone, prednisone, streptomycin, tetracycline, and testosterone.

Similarly, utilizing the hydrogen bonding between PVP molecules and drug molecules can achieve a delayed and sustained release effect opposite to solubilization and quick acting, controlling the degree of association between PVP molecules and drug molecules. This can slow down the release of drug molecules in the human body after association, delay their dissolution rate, and prolong drug efficacy. PVP has the effect of prolonging the efficacy of drugs such as penicillin, chloramphenicol, insulin, sodium salicylate, procaine, and cortisone.

PVP can be used not only as a binder, solubilizer, disintegrant, and delay agent in solid drugs, but also as a drug film coating, drug capsule shell, and controlled release film. The outer layer of the drug film and capsule shell made of PVP are not easily broken in a dry environment. The appropriate amount of PVP, together with other insoluble polymers, can be used to make permeable membranes of different thicknesses and pore sizes, which can adjust the rate of drug passage through the membrane and achieve controlled release efficacy.

Application of PVP in Liquid Pharmaceuticals

In addition to the various applications of PVP in solid drugs mentioned above, PVP also plays an important role in injections and eye medicines. For example, PVP is used in some injection solutions. Due to its binding effect with drugs, it plays a solubilizing role on the one hand, and on the other hand, for certain drugs that will crystallize or precipitate if left for too long, PVP can play a dispersing and stabilizing role. PVPK17 can be used in eye drops to reduce eye irritation and prolong the duration of eye drops.