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Plasdone® Povidones

Product Overview

High-performance polymers Plasdone polymers possess unique physical and chemical properties, making them useful in a variety of pharmaceutical dosage forms. A series of synthetic homopolymers of N-vinyl-2-pyrrolidone (Figure 1), Plasdone polymers are highly adhesive, readily soluble in water and solvents, physiologically inert, nonionic, nontoxic, temperature resistant and pH stable. This unique combination of properties is the result of the pyrrolidone ring, which imparts water solubility and solvent- and surfactant-like properties for high adhesion and interfacial activity. Figure 1: Chemical structure of Plasdone polymer

Benefits
Provides excellent adhesive properties as a wet granulation tablet binder Enhances solubility and bioavailability of drug actives

n

Inhibits crystallization of drug actives and inactive ingredients Dissolves quickly in water Modifies solution viscosity Forms water-soluble bioadhesives and films

Pharmaceuticals
Low and high molecular weights As physical and mechanical properties vary with a polymer’s molecular weight, Plasdone polymers are manufactured in a variety of molecular weight grades to best meet the requirements of each application. In general, as the molecular weight of the polymer increases, the solution viscosity, glass transition temperature and adhesive properties increase. As the molecular weight decreases, the rate of polymer dissolution, oral absorption and excretion increase. The average molecular weights, for the commercial grades of Plasdone polymers measured by light scattering, are shown in Table 1. Historically, it was difficult to determine the molecular weight of povidone polymers directly. Thus, the K-value was adopted to classify the various molecular weights of Plasdone polymers. The K-value, a function of the average degree of polymerization and the intrinsic viscosity of the polymer, is calculated from the kinematic viscosity of a aqueous polymer solution. Table 1: Plasdone K polymers are available in a range of molecular weights for use in pharmaceutical applications
Product K-Value Weight Average Molecular Weight (Mw) 10,000 Tg (⁰C) Applications

Pyrogen-free options For applications where pyrogens are of concern, Plasdone C polymers (Table 2) are supplied with low endotoxin levels. These grades are preferred for parenteral and ophthalmic applications. Table 2: Plasdone C polymers are “pyrogen-free “
Product Name K-Value Weight Average Molecular Weight (Mw) 4,000 10,000 58,000 Typical Pyrogen Endoxtoxin Units

Plasdone C-12 Plasdone C-17 Plasdone C-30

10.2-13.8 15.5-17.5 29-32

0.5 max 0.5 max 0.5 max

Plasdone K-12 10.2-13.8 4,000 Plasdone K-17 16-17.5

120 126

Low-viscosity, excellent solubilization/ crystal inhibition properties for liquidfilled soft-gelatin capsules Low-viscosity, wet granulation tablet binder (3-6% use level) Low-viscosity, excellent wet granulation tablet binder at 2-5% use level; Excellent solubilization/crystal inhibition properties and fast dissolution for use in spray-dried and melt-extruded solid dispersions High-viscosity, wet granulation tablet binder; excellent tablet binder for high-dose, poorly compressible actives

Powders with good flow for ease of manufacturing All Plasdone polymers with the exception of Plasdone K-90 and K-90D polymers are supplied as spray-dried powders with spherical particles that exhibit excellent flow properties and are well-suited for powder blending. As an example, Plasdone K-29/32 particles appear spherical when examined under a scanning electron microscope (Figure 2A). Plasdone K-90 polymer is a flaky powder (Figure 2B) while Plasdone K-90D polymer is higher in density and has more rounded particles (Figure 2C) for easier and faster dispersion. Plasdone K-90 and K-90D polymers are chemically identical; Plasdone K-90D polymer has been densified. Typical average particle sizes, typical tap and bulk densities for the various Plasdone grades are reported in Table 3. Figure 2: Plasdone particle morphology
A. B.

Plasdone K-25 24-26

34,000

160

Plasdone K-29/32

29-32

58,000

164

C.

Plasdone K-90 85-95 and K-90D

1,300,000

174

A. Plasdone K-29/32 polymer is free-flowing with spherical particles B. Plasdone K-90 polymer is a fine, free-flowing, flaky powder C. Plasdone K-90D polymer has been densified for faster dispersion

Pharmaceuticals
High degree of compatibility Plasdone polymers are compatible with a wide range of materials as demonstrated by their tolerance for pH changes and salts. The insensitivity of a 5% aqueous solution of Plasdone K-29/32 polymer to changes in pH is shown in Figure 4. Figure 4. The viscosity of an aqueous Plasdone K-29/32 polymer solution is not affected by changes in pH

Table 3: Plasdone particles have excellent flow
Product Name Typical Typical Tap Average Density Particle Size (g cm-3) (microns)* 50 50 60 200 300 0.54 0.60 0.49 0.47 0.46 0.53 Typical Bulk Density (g cm-3)

Plasdone K-12 Plasdone K-17 Plasdone K-25 Plasdone K-90 Plasdone K-90D

0.42 0.44 0.38 0.36 0.40 0.32

Plasdone K-29/32 80

* Results are typical median (D50)

Solubility and solution viscosity Plasdone polymers are completely soluble in water at room temperature. The maximum concentration of polymer soluble in water is limited only by the viscosity at a given concentration. The viscosity of an aqueous solution depends on the molecular weight of the polymer (Figure 3). In addition to water, Plasdone polymers are soluble in a wide variety of organic solvents at room temperature. The viscosity of the solution is related to the viscosity of the solvent selected, the molecular weight of the polymer and concentration. Figure 3: The higher molecular weight Plasdone K-90 polymer provides the highest aqueous solution viscosity

Viscosity of 5% aqueous solution of Plasdone® K-29/32 at room temperature (cP)

pH

Furthermore, the appearance and properties of a 1% aqueous solution of Plasdone K-29/32 polymer are unaffected by the addition of various salts, including aluminum sulfate, calcium chloride, sodium phosphate, ammonium chloride, sodium chloride and zinc sulfate – suggesting that Plasdone polymers will not interact with ionic drug actives or their salts. Plasdone polymers have been found to be compatible in solution and in solid state with a wide variety of materials including carboxymethylcellulose (low-viscosity grade), ethylcellulose, methylcellulose, polyethylene glycol, polyvinyl alcohol, sodium alginate and sodium lauryl sulfate. A long history of use For over 50 years, Plasdone polymers have been widely used in a variety of pharmaceutical and dietary supplement dosage forms. Plasdone polymers conform to the current USP/NF, Ph. Eur and JPE monographs for povidone (Table 4).

Brookfield Viscosity (mPa s) at 25˚C

Concentration (%w/w)

ISP’s Plasdone C and K polymers have received the United States Pharmacopeia (USP) Verified Pharmaceutical Ingredient Mark. In addition, ISP’s Plasdone C and K products hold certificates of suitability from the European Directorate for Quality of Medicines (EDQM). Plasdone polymers are listed in the United States Food and Drug Adminstration’s (US FDA) Inactive Ingredient Guide. ISP maintains a Drug Master File with the US FDA.

Pharmaceuticals
A toxicity and safety profile for Plasdone polymers is available on request. Table 4. Pharmacoepial monograph compliance
Product Name Pharmacopeial Monograph USP/NF Plasdone C-12 Plasdone C-17 Plasdone C-30 Plasdone K-12 Plasdone K-17 Plasdone K-25 Plasdone K-29/32 Plasdone K-90 and K-90D 3 3 3 3 3 3 3 3 Ph. Eur. 3 3 3 3 3 3 3 3 JP/JPE NA* 3 (JPE) 3 NA* 3 (JPE) 3 3 3

Applications Plasdone polymers are highly versatile excipients used in a wide range of pharmaceutical applications, including but not limited to: • Plasdone K polymers with their excellent adhesive properties and solubility are the premier, high-performance binders for wet granulation. Their use produces robust tablets with low friability and reproducible dissolution characteristics. • Plasdone polymers improve the solubility of, and enhance bioavailability of APIs. There are several examples available in the literature where Plasdone polymers improve the solubility of a drug through co-mixing, co-melting or co-precipitation to form solid dispersions. • In oral liquids, Plasdone polymers are used as a crystal growth inhibitor to prevent crystallization of inactive ingredients that result in cap-blocking. • Plasdone polymers stabilize suspensions, dispersions and emulsions. Plasdone polymers absorb as a thin layer on the surface of the colloidal particles, thus preventing contact with other colloidal particles, effectively stabilizing the formulations. • Plasdone polymers have been shown to enhance the solubility of actives and produce highly concentrated solutions that can be used to fill soft gelatin capsules. • When added in ophthalmic preparations, Plasdone polymers are used to increase the viscosity of drug solutions and contact time with the eye and improve lubricant effectiveness. • Low molecular weight Plasdone polymers are used as solubilizers, crystal growth inhibitors and dispersion aids in injectable products for human and veterinary drugs.

*Currently, the JP monograph only defines Povidone grades with a nominal K-value of not less than 25 and not more than 90. The JPE defines an additional Povidone grade with a nominal K-value of 17.

Key product specifications
Plasdone K-12 Appearance % Moisture pH (5% aqueous solution) Vinyl Pyrrolidone (ppm) % 2-pyrrolidone Peroxide Content (ppm) 5 max 3-5 5 max 0.99 max 400 max Plasdone K-17 Plasdone K-25 Plasdone K-29/32 Plasdone K-90 and K-90D 5 max 4-7 10 max 0.99 max 400 max

White to creamy white powder 5 max 3-5 5 max 3 max 400 max 5 max 3-5 5 max 3 max 400 max 5 max 3-5 5 max 3 max 400 max

Complete product specifications are available on request.

To find additional ISP sales offices visit: isppharmaceuticals.com
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Product Code: PH5768-04/2010
The information contained in this document and the various products described are intended for use only by persons having technical skill and at their own discretion and risk after they have performed necessary technical investigations, tests and evaluations of the products and their uses. While the information herein is believed to be reliable, we do not guarantee its accuracy and a purchaser must make its own determination of a product’s suitability for purchaser’s use, for the protection of the environment, and for the health and safety of its employees and the purchasers of its products. Neither ISP nor its a liates shall be responsible for the use of this information, or of any product, method or apparatus described in this document. Nothing herein waives any of ISP’s or its a liates’ conditions of sale, and WE MAKE NO WARRANTY, EXPRESS OR IMPLIED, OF MERCHANTABILITY OR FITNESS OF ANY PRODUCT FOR A PARTICULAR USE OR PURPOSE. We also make no warranty against infringement of any patents by reason of purchaser’s use of any information, product, method or apparatus described in this document.

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