Application of povidone in pharmacy

PolyvinylPyrrolidone, English name: PolyvinylPyrrolidone, referred to as PVP, is an excellent performance, a wide range of non-ionic water-soluble polymer fine chemicals, from N-vinylpyrrolidione (N-Vinylpyrrolidione, referred to as NVP) by free radical polymerization. PVP has many excellent physical and chemical properties, such as excellent solubility, low toxicity, film forming, solubilization, complexation, physiological compatibility, surface activity and chemical stability.
【 Key words 】 POvidone, medicinal
With the development of pharmaceutical preparation technology, POvidone has been used more and more widely as pharmaceutical excipients of non-ionic water-soluble polymer compounds.
The excellent physiological compatibility of POvidone series of pharmaceutical excipients is its inherent and unique product properties, and now it has become the three main synthetic pharmaceutical excipients together with cellulose derivatives and acrylic compounds.
Povidone series can be divided into a variety of models according to different K values, of which the most widely used varieties are K15, K30 and K90. The Chinese Pharmacopoeia only lists the quality standard of K30, while the British and American pharmacopoeia lists all POvidone K series as a whole standard. At present, POvidone, as a pharmaceutical excipient, has many preparations.
one. The application of PVP in tablets

1.1 Adhesive
In tablet manufacturing, K25 or K30 is usually used. PVP is widely used as a viscosifier for tablets, granules, etc. The dosage is generally 3 ~ 5%(W/W), and the concentration of adhesive solution is 0.5 ~ 5%(W/W). The amount of PVP used can directly affect the tensile strength of the film, generally the more the amount of PVP, the greater the tensile strength of the film. Different addition methods, namely internal addition or external method, will affect the disintegration time of tablets. Internal addition means that PVP is mixed with drug powder in dry powder state and then wet with water or organic solvent for granulating. External method means that PVP is dissolved in organic solvent or water and then added into the mixed drug powder. WanLSC et al. showed that the disintegration time and dissolution rate of the film made by internal adhesive were longer than that by external method. Internal addition is especially suitable for extractum viscera and drugs with high hygroscopic properties. Fluidized bed spray drying granulation (referred to as one step granulation) is used
At present, a new technology in tablet pelletizing process, in the fluidized bed pelletizing with PVP as the binder, the PVP concentration, volume, spray speed, and loading amount will affect the properties of the prepared particles, and the high quality particles can be prepared with low concentration, small volume, small spray speed, and large loading amount. The method is suitable for many varieties.
There are many varieties of PVP as tablet adhesive in foreign countries, which are generally mixed with starch, hydroxypropyl methyl cellulose, micro-powder silica gel, etc., which can improve the compressibility and dissolution performance during tablet pressing.
For drugs sensitive to moisture and heat, organic solution of PVP (generally ethanol solution) can be used for granulation. This avoids the influence of moisture and allows the fork to dry quickly at lower temperatures.
For hydrophobic drugs, it is suitable to use the water dissolution of PVP as a binder, so that the cloth is easy to be evenly wet, and the surface of the liquid drug can become hydrophilic, which is conducive to the dissolution of the drug and the disintegration of the tablet.
For effervescent tablets. Generally, the effervescent tablets contain a mixture of sodium bicarbonate and citric acid, and the acid-base reaction will not occur when the anhydrous ethanol solution of PVP is used for granulation. Using 5%PVP anhydrous ethanol solution as the adhesive containing Vitaxol C effervescent tablets, the prepared particles have good compressibility, rapid dissolution and strong foaming effect.
PVP/VA also known as Vinylpyrrolidone vinyl acetate copolymer (Vinylpyrrolidone – VinylAcetateCopolymer, VPVAC, CAPE), is a new product developed on the basis of PVP, for white granular powder, odorless, tasteless, non-moisture absorption. Soluble in water, hydrous alcohol, anhydrous ethanol. It is the best adhesive for the preparation of effervescent tablets using anaqueous ethanol as solvent wet mixing granulation, the advantages are non-moisture absorption, good compressibility, beautiful tablets, as the adhesive concentration is generally 5% ~ 10%, the dosage is generally 2% ~ 5%.
For chewable tablets. Especially good adhesive for acid tablets such as aluminum hydroxide. It can solve the problem of water sensitivity of drugs. In order to prevent the tablets from gradually hardening during storage, 2%-3% glycerol can be added to PVP solution.
For carbon flakes. As an adhesive for carbon sheets, it can not only improve the peeling phenomenon in the process of tablet pressing, but also make the tablet disintegrate quickly and make the adsorption capacity particularly strong.
For direct compression. PVP dry powder can also be used as a dry adhesive for direct tablet pressing. If there are more hydrophobic drugs in the tablet prescription, it is easy to produce the phenomenon of falling tablet when pressing the tablet. If 2% ~ 3% PVP dry powder is added (with K25 specification). This situation can be improved, and the amount of anti-stick agent and lubricant should be increased appropriately to avoid sticking.
For dispersing tablets. Because PVP is soluble in water, it is often used as a binder for dispersing tablets.
1.2 Disintegrators
Department of PVPP in PVP on the basis of the development of new products, for the vinyl which luo high molecular weight of alkane ketones crosslinking, also called cross-linked polyvinylpyrrolidone (Crospovidone, Cross – linkedpolyvinylpyrTolidone). It is a white powder with good fluidity. Due to its high molecular weight and cross-linked structure, it is insoluble in water, but it can quickly introduce water when it encounters water, and the swelling volume increases by 150% to 200%, which promotes the expansion of its network structure and produces disintegration. Because it does not produce a high-viscosity gel layer when water-soluble polymers (except starch) swell after water absorption, it does not affect the continued disintegration, so it is often used as a disintegrator of tablets, and its effect is better than that of disintegrators such as starch or sodium alginate. Although the hardness of the tablet increases with the increase of the pressure when pressing the tablet containing this product, the disintegration time is rarely affected by the pressure. The disintegration time is still faster than tablets containing the same amount of starch, modified starch, crosslinked carboxymethyl fiber cable and methyl cellulose under the same pressure. USP XI and NF have collected PVPP as disintegrators, fillers and excipients of tablets, with the usual dosage of 20~80mg/tablet.
1.3 Coating materials
The addition of PVP in tablet sugar-coated paste or film coating solution can increase the adhesion of coating material to the substrate, and PVP can also be used as a pigment dispersant in colored film coating solution to make the pigment distribution uniform. When used as coating, it can produce bonding phenomenon, and it is slightly softened in humid air after coating. It is advisable to add appropriate amount of shellac, glycerin monoacetate vinegar, etc., to improve hygroscopic property, and PEG6000 to increase the flexibility of the film.
1.4 pore-causing agent for skeletal sustained release tablets
Skeleton sustained-release tablets are a class of solid preparations prepared by melting, dissolving volatile solvent or direct pressing after mixing drugs with insoluble polymers and water-soluble substances (pore inducing agents). PVP can be used as the matrix pore inducing agent to prepare insoluble skeleton sustained-release tablets and soluble skeleton sustained-release tablets. Dakkuri et al studied the effect of butyl PVP as a pore-forming agent on the release of N-benzyl-N ‘, N ‘-dimethyl-N – (2-pyridyl) ethylenediamine hydrochloride skeleton sustained release tablets. The sustained release tablets were prepared by melting method. Compared with the prescription without PVP, the 8h release of 5% PVP prescription increased by 37%, and 20%PVP prescription increased by 55%. When l0% ~ 20%PVP is added, the dissolution mode is optimized and the drug is released at a rate of 10% / h. However, if the sustained release tablets were prepared by direct pressing method, whether PVP was added or not and how much was added would not affect the drug release. Therefore, when PVP is used as the pore inducing agent of the skeleton sustained release tablets, both the preparation process and the amount of PVP can affect the dissolution of the tablets. At present, PVP has been used as pore inducing agent to make butadiene, indomethacin, zinc sulfate, ibuprofen and other sustained-release tablets.
two. The application of PVP in injection
3.5%(w/v) isotonic infusion of PVP can be used as a blood volume supplement, which is now rarely used. In the aspect of injection, it is widely used as a co-solvent, dispersant and delay agent. In foreign countries, PVP is added in powder injection such as doxycycline powder injection of Pfizer and Rifampicin powder injection of Merck. The use of L0-25pvp solution can make penicillin, cortisone, procaine, insulin and other drugs in the body slowly release, prolong the effect. When PVP was added to chloramphenicol suspension for injection as a protective colloid and dispersant, the fineness of the product was less than 5 microns. The general dosage in suspension is 0.1% ~ 1%.
Three. The application of PVP in capsules
When filling capsules, if the light main drug powder with small gravity and easy to produce electrostatic effect can be added to 1% ~ 2%PVP ethanol solution to help granulate, so as to improve the flow performance of the powder and facilitate filling. In foreign countries, PVP has been used as hard capsule excipients, such as cyclomandelate, propylpyramine, pyridoxate, ethyl poppy long-acting capsule and so on. It has been reported that crosslinked PVP, or PVPP, is the antipyretic analgesic ketorolac aminotriol.
There are few reports on the application of PVP in the formulation of soft pellets. A small amount of PVP(about 0.2%) was added as a dispersant when the Japanese chemical pharmaceutical company prepared nitrophenidine soft pellets.
Four. Application of PVP in eye drops and other solutions
Adding a certain amount of PVP into the eye drops can reduce the irritation of the drops, prolong the stay time of the drug in the eye, and improve the curative effect. Because PVP is hydrophilic, it can make contact lens wearers feel comfortable and can double as artificialtears.
In recent years, nasal mucosal administration has attracted people’s attention. For those drugs such as propranolol, which have a large liver-crossing effect or irritant to the stomach, nasal mucosal administration can be used to play a systemic role. In order to reduce the irritation of the drug on the nasal mucosa and prolong the effect. A certain amount of PVP can also be added to the nasal mucosa.
PVP can also be used as a suspension agent for syrups.
Five. PVP as a drug carrier
5.1 PVP forms a solid dispersion with insoluble drugs
Solid dispersions have rapid effect and improved bioavailability, so there has been a certain development in the past 30 years. At present, the varieties studied and applied in China are gradually increasing, and PVP is widely used in solid dispersions as the main carrier. When PVP is used as the carrier to form a co-precipitate with drugs, such as vanillin and PVP(1:10), the solubility is 4.08 mg/mL, and 82% has been dissolved in 10min, while vanillin and PVP(1:10) mechanical mixture or pure vanillin, both of which are not dissolved.
The drug release rate of solid dispersion can be adjusted by changing the molecular weight (polymerization degree) or the dosage ratio of PVP.
The general rule is that with the increase of molecular weight of PVP, the dissolution rate of drugs decreases. For example, the dissolution rate of dispersions formed by ST, SMZ and SIZ with PVPk15(10000), PVPk30(40000) and PVPk90(360,000), respectively, is PVPk15>PVPk30>PVPk90. Other PVP solid dispersions that conform to this rule include dihydrochlorothiazide, sulfathiazole, chloramphenicol, furoid, digoxin, chlorothiazide, hydrocortisone, strong orange, etc., but there are also some solid dispersions of drugs that do not conform to this rule, such as nitrophenyliasis and the above three PVP prepared dispersions, the dissolution test results show that PVP dispersions dissolve the fastest. The 10% phenytoin-pvp dispersion is PVPk30>PVPk25>PVPk60, which is because PVP requires a certain chain length (polymerization degree) to form a network on drug molecules, and different drugs require different PVP chain lengths, so PVP has different effects on the inhibition of crystallization of different drugs.
If the weight ratio of drug to PVP dispersion is different, the dissolution rate is also different. For example, when the weight ratio of sulfamisoxazole to PVP is 10:1, the amount of PVP is too small to inhibit the crystallization of sulfamisoxazole. Can not form a coprecipitate, generally 14 or 1:5 (W/W) is appropriate. Another example is cyclohexylurea acetoxy-PVP dispersion system, the content of PVP is more than 70%, the drug is dispersed in amorphous form, and the dissolution is rapid, while the drug crystallization increases and the dissolution decreases when the PVP is lower than 70%. The dissolution rate of griseofulfiin-PVP dispersion was 1:20 > 1:10 > 1:5, while the dissolution rate of SF-PVP co-evaporation was 1:3 > 1:5 > 1:10 > 1:20.
5.2 Controlled release film components
PVP is often used as a controlled release film component of transdermal absorbent film. The general transdermal drug delivery system can be divided into 5 layers: mounting layer, drug library, controlled release film, adhesive layer and protective film. For the microporous membrane controlled release system, it uses a dense or porous film as a controlled release element, and the drug reservoir is wrapped in a small pool made of a metal plastic composite film and a rate-controlled polymer film molded. Part of the drug solids in the reservoir are a pasty suspension coated in a solid medium or suspended in a viscous medium that cannot seep out. Controlled release film is a layer of microporous or non-porous polymer film, it has a certain permeability to drugs, can be controlled by controlling the type of polymer in the controlled release film (commonly used hydroxyethyl cellulose, hydroxypropyl cellulose, PVP, polyvinyl alcohol, etc.), viscosity level, proportion of the drug release in the film. Bhalla et al. studied the transdermal film agent of chlortramitone maleate, and used the film formed by PVA, PVP and glycerol or polyvinyl alcohol as the polymer matrix of the transdermal absorption preparation of the drug. The results showed that the transdermal absorption could be increased by increasing the concentration of PVP or the amount of plasticizer.
In the trial production of long-release eye film, PVP was added to the controlled release layer as a pore-inducing agent, which could be well mixed with ethylene vinyl acetate copolymer (EVA), and the eye film made was brighter and softer than that made with dextrin.
5.3 Others
PVP is also used in other dosage forms, and it has been reported that PVP can be used as an ointment substrate for oral mucosa and an implant carrier. Due to its good film forming and chemical stability, PVP can also be used as a water-soluble capsule material for micro-capsules, and the drug release can be controlled by changing the thickness of the capsule.
In short, the application prospect of PVP is broad, due to both hydrophilic and hydrophobic characteristics, according to the degree of polymerization can be made into different molecular weight products, and chemical stability, as a pharmaceutical preparation, especially the new supplement used in solid preparations, PVP series products will be widely used together with fiber, acrylic ester, etc. It plays an active role in China’s pharmaceutical preparations entering the international advanced ranks and makes significant contributions to the development of China’s pharmaceutical industry.