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Crospovidone Excipient | Uses, Suppliers, and Specifications

Crospovidone is a crosslinked and insoluble polyvinyl pyrrolidinone polymer. Owing to its insolubility and high swelling properties, it is used as a superdisintegrant. Unlike Povidone, it is not described in terms of a K-value or molecular weight, and instead, according to particle size. Crospovidone is supplied as a white or almost white, almost odourless hygroscopic powder.

Synonyms and Trade Names: Crosslinked Povidone; Crosslinked Polyvinylpyrrolidone; Insoluble Polyvinylpyrrolidone; Kollidone® CL; Crospovidone XL; PLASDONE™ XL

Pharmacopoeia Compliance: USP-NF; Ph. Eur; JP; IP; FCC

Uses & Applications: Disintegrating Agent; Suspending Agent and Viscosity-increasing Agent and Solubilising Agent for Poorly Soluble Drugs

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Crospovidone SL- JH Nanhang

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Crospovidone XL - JH Nanhang

Crospovidone XL10 - JH Nanhang

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Description

Crospovidone is a water insoluble synthetic cross-linked polyvinyl pyrrolidone. Under microscopical examination, Crospovidone appears in the form of spherical particles of approximately 5µ which may be joined into larger, porous agglomerates, some with diameters in excess of 200µ. In the USP-NF and Ph.Eur Crospovidone is described as a water-insoluble synthetic cross-linked homopolymer of N-vinyl-2-pyrrolidinone.

Crospovidone (together with the other polyvinylpyrrolidone polymers, Povidone and Cospovidone) is among the several innovations first commercialised by BASF in the early 1930s as part of the company’s acetylene chemistry programme (started and led by the chemist, Walter Reppe). The synthetic pathways developed under the Reppe programme are still used today to produce polyvinylpyrrolidones (the so-called Reppe method).

The main difference between Povidones and Crospovidone is that Crospovidone is manufactured by a polymerization process that results in a cross-linked povidone analogue. The reaction is undertaken in an aqueous medium and no organic solvents or radical starters are used. The cross-linking process is both chemical and physical, with the latter mechanism, which is achieved mainly via polymer chain entanglement, dominating the material’s properties. More details about the chemistry of Crospovidone can be obtained through this link.

Owing to the insolubility of Crospovidone in all the standard solvents, it is not possible to describe the material in terms of a K-value or molecular weight. Instead, the different grades are differentiated mainly by the particle size distribution into two main types: Type A (Standard), and Type B (Fine, Superfine and Micronised). Their main differences are shown below:

Type A Type B
Grade Standard Fine Super Fine Micronised
Particle size (µ) 40 – 140 20-100 30 – 100 <10
Swelling pressure (kPa) 170 30 25 70

Crospovidone is supplied as a white to creamy-white, fine, free-flowing, practically tasteless, and odourless but hygroscopic powder.

Chemical Structure & Identifiers


Chemical Name 1-Ethenyl-2-pyrrolidinone homopolymer
CAS Registration Number [9003-39-8]
Empirical Formula (C6H9NO)n
Molecular weight Greater than 1 000 000
EINCES Number 618-363-4
UNII Code (FDA) 2S7830E561

Regulatory Status

Crospovidone is an approved pharmaceutical excipient. It is listed in all major pharmacopoeia, including the United State Pharmacopoeia-National Formulary; the European Pharmacopoeia, and the Japanese Pharmaceutical Excipients compendia. Additionally, it is included in the US FDA Inactive Ingredients database for the following dosage forms:

  • Oral capsules, granules and tablets
  • Sublingual tablets
  • Effervescent tablets

Povidone is also an approved food ingredient, for which a monograph exists in the Food Chemicals Codex (FCC).

Physicochemical Properties

Physical form Solid, powder
Appearance White to creamy-white, finely divided, free-flowing, powder
pH value (1% slurry) pH=5.0-8.0
pKa Not available
Bulk density 0.15–0.28 g/ml depending in type and grade
Tapped density 0.18–0.55 g/ml depending on type and grade
True density 1.22 g/ml
Melting point Softens at 150 oC
Moisture content Very hygroscopic. Crospovidone absorbs significant amounts of moisture and swells substantially even at low relative humidity.
Particle size distribution Micronised grades typically 2-9 µm. Coarse grades 20-100 µm.
Solubility Insoluble in water, alcohol, ethyl acetate and acetone
Swelling pressure (kPa) 170 (Type A – Standard grade)

25-30 (Type B – Fine & Super Fine grades)

70 (Type B – Micronised grades)

Hydration Capacity (g of water /g of polymer) 3.5-5.5 (Type A)

3.0-4.5 (Type B Micronised grades)

5.0-8.5 (Type B – Fine & Super Fine grades)

Specific surface area (m2/g) <1 m2/g (Type A)

1.5 m2/g (Type B Micronised grades)

3-6 m2/g (Type B – Fine & Super Fine grades)

Time to reach 90% of maximum swelling pressure 10 s (Type A – Standard grade)

15 – 35 s (Type B – Fine & Super Fine grades)

Pharmacopeoeal Specifications

USP-NF Ph.Eur
Name Crospovidone Crospovidone
Authorised use Excipient Excipient
Identification A, B A, B, C, D, E
Characters

Appearance

n/a White or yellowish-white powder or flakes
Solubility n/a Practically insoluble in water, alcohol or methylene blue
Peroxides n/a ≤400ppm
Water-soluble substances ≤1.50% ≤1.0%
Impurity A ≤0.1% ≤10ppm
Heavy metals ≤0.001% ≤10ppm
Loss on Drying n/a ≤5%
Residue on ignition ≤0.40% n/a
Sulphated ash n/a ≤0.1%
Assay (nitrogen content) 11.5 – 12.8% 11.5 – 12.8%
Labelling specified n/a

Key: n/a Specification is not listed

*All claims with respect to conformity are subject to our Terms and Conditions. No express or implied warranty is made for specific properties or fitness for any particular application or purpose.

Applications in Pharmaceutical Formulations or Technology

Crospovidone grades are used in pharmaceutical formulations on account of their swelling properties, porosity and insolubility. The different uses include:

  • Superdisintegrants for fast and efficient tablet disintegration
  • Drug release and bioavailability enhancement of certain active ingredients through complexation
  • Stabilisers for suspensions through the ability to form flocs

Use of Crospovidone as a Superdisintegrant

Upon contact with water, Crospovidone absorbs water via capillary action and regains its normal structure releasing an amount of energy capable to break the tablet. The particle size of crospovidone strongly affects the disintegration process, and larger particles provide a faster disintegration. As particle size increases, the intra-particular porosity increases, leading to larger water uptake and faster disintegration.

In the presence of moisture, water molecules are absorbed into the porous structure of the material’s agglomerates, which causes the lattice structure to expand. This causes high stress to build on surrounding core ingredients. This, in addition to the porous nature of the particles, allows the polymer to wick water, leading to disintegration of the tablet.

As a superdisintegrant, Crospovidone is recommended to be used at 2—5% as a proportion of the tablet weight, whether prepared by direct- compression or wet- and dry-granulation methods. Higher superdisintegrant levels do not necessarily lead to faster disintegration, and may indeed, lead to weaker tablets.

Generally, Crospovidone grades with larger average particles provide faster disintegration rates compared with grades with smaller particles. However, finer-grained grades or those with narrow particle size distributions are recommended for use for small tablets with low API concentrations.

Advantages of Crospovidone

  • High capillary activity and pronounced hydration capacity, with little tendency to form gels.
  • Unlike other disintegrants, Crospovidone can enhance the release and the bioavailability of drugs through complex formation
  • Owing to high water-binding properties Crospovidone can stabilise water-sensitive drugs in solid dosage forms, e.g. in vitamin formulations
  • Highly compressible and particularly suited for actives or formulations with plastic or poorly compactible characteristics
  • Crospovidone grades are non-ionic, and thus do not form complexes with ionic drugs, which can impact drug release and/or stability for cationic drugs. Moreover, disintegration is unaffected by the pH of the medium.
  • Yields smooth tablets

Crospovidone is unique among superdisintegrants because it acts via multiple disintegration mechanisms including swelling, and wicking followed by secondary swelling.

In general, an increase in particle size improves the disintegration and dissolution of tablets. This effect is attributed to the efficient formation of hydrophilic networks by larger size particles.

Like other disintegrants, Crospovidone is more effective if used both intra- and extra-granularly. In general, disintegrants added exclusively intra-granularly are not as effective as that added extra-granularly.

Storage conditions do not appear to affect the water uptake and force development for Crospovidone as much as they do for Sodium Starch Glycolate.

The presence of other excipients such as lubricants can impact the efficiency of disintegrants. This is especially the case with lubricants, which can interfere with wetting and water entry.

The solubility of excipients also has an impact on how efficient disintegration proceeds. Generally, insoluble excipients enhance disintegration and dissolution.

Use of Crospovidone to Stabilise Suspensions

Micronised Crospovidone (Type B) can be added in concentrations of 5 – 12% to oral and topical suspensions to stabilise oral and topical formulations. This grade achieves this effect by increasing the volume of the sediment and reducing its sedimentation rate, and by making it easy to redisperse the sediment by shaking (anticaking effect). These effects are achieved without increasing the formulation’s viscosity.

The ability to stabilise suspensions without increasing thickness is particularly useful in ready-to-use suspension or an instant drink-type powder or granulate formats that require the consumer to prepare before use.

The addition of electrolytes such as sodium citrate as well as xanthan gum or sugar syrups is recommended as it increases the sediment volume achieved with Crospovidone in these formulations.

Safety and Precautions

Crospovidone has been used in oral pharmaceutical formulations for several decades and is generally regarded as a nontoxic and non-irritant material. Short-term animal toxicity studies did not show any adverse effects associated with crospovidone. However, there are not enough data to permit the assignment of an acceptable daily intake value in humans.

Toxicology: Mouse toxicity studies have shown to be as follows: LD50 (mouse, IP): 12g/kg. Not a known carcinogen.

However, when handling Crospovidone observance of the prevailing SHEQ protocols appropriate to the circumstances and quantity of material handled is recommended. Eye protection, gloves and a dust mask should be used.

Stability and Storage Conditions

Crospovidone is highly hygroscopic and absorbs significant amounts of moisture (25% water uptake at 75% RH). Storage conditions selected should prevent contact with the atmosphere for prolonged periods of time. Crospovidone has an expected shelf life is 3 years. Over time, residual peroxides increase, which can affect the stability of oxygen-sensitive molecules.

Sustainability and Environmental Impact

Crospovidone is an artificial polymer obtained through chemical synthesis. Being an inert and non-toxic excipient it is considered safe for the environment, with minimal long-term impact on ecology or marine life. Crospovidone excipient grade achieved a total score of 71/100 by the Excipients Forum Sustainable Chemistry Score™.

 

Manufacturers & Suppliers

BASF Corporation

  • Kollidon® CL (Type A)
  • Kollidon® CLF (Type B)
  • Kollidon CL-SF (Type B)
  • Kollidon® CL-M (Type B – Micronised)

Ashland Inc (ex ISP)

  • Polyplasdone™ Ultra
  • Polyplasdone™ XL
  • Polyplasdone™ Ultra-10
  • Polyplasdone™ XL-10

Ultra grades correspond to Type A while Ultra 10 grades correspond to Type B

JH Nanhang Life Sciences Co. Ltd

  • Crospovidone XL (Type A)
  • Crospovidone XL-10 (Type B)
  • Crospovidone SL (Type B – Micronised)

Additional Resources (Downloads)

References and Literature Used

[1] V. Bühler, Polyvinylpyrrolidone Excipients for Pharmaceuticals: Povidone, Crospovidone and Copovidone, Springer Science & Business Media 2005.

[2] T. Dürig, K. Karan, Binders in Wet Granulation, Editor(s): Ajit S. Narang, Sherif I.F. Badawy,Handbook of Pharmaceutical Wet Granulation, Academic Press, 2019, Pages 317-349. https://doi.org/10.1016/B978-0-12-810460-6.00010-5. (https://www.sciencedirect.com/science/article/pii/B9780128104606000105).

[3] V. Busignies, V. Mazel, H. Diarra, P. Tchoreloff, Prediction of the compressibility of complex mixtures of pharmaceutical powders, Int J Pharm, 436 (2012) 862-868. https://doi.org/10.1016/j.ijpharm.2012.06.051. Pubmed Google Scholar

 

FAQS

What is Crospovidone?

Crospovidone is a water insoluble synthetic cross-linked polyvinylpyrrolidone that is commonly used as a disintegrating agent in tablets. it is obtained synthetically using a process that is similar to that used to synthesise povidone.

 

What are the uses of Crospovidone?

Crospovidone is used as a superdisintegrant in tablets and capsules. Similar to sodium starch glycolate, Crospovidone disintegrates tablets mainly by swelling, with little tendency to form gels.

 

How safe is Crospovidone?

Copovidone has been used in pharmaceutical products over several decadees and been found to be safe with no toxicological reports.

 

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