description Plasdone™ S630 Ultra is a new and improved version of copovidone. Designed to provide better performance in tablet formulations, hot melt extrusion (HME) and continuous processing, it offers superior benefits compared to the original Plasdone™ S630 copovidone.

Like the original, Plasdone™ S630 Ultra copovidone is a 60:40 random, linear copolymer produced by the free radical polymerization of N-vinyl-2-pyrollidone and vinyl acetate (Figure 1). Both monomers impart important properties that define the polymer’s performance characteristics. The pyrrolidone ring is responsible for excellent water solubility, adhesion, film forming and solubilization properties, while the vinyl acetate monomer reduces glass transition temperature (Tg) and hygroscopicity compared to homopolymers of pyrrolidone (PVP). Well-known in the industry as a multipurpose excipient, copovidone functions as a binder, solubilizer/solid dispersion carrier and film former in a variety of pharmaceutical formulations.

improved processability and stability

plasdone™ S630 ultra copovidone

key features and benefits¢excellent for oxidative sensitive APIs with greater

long-term stability.

¢efficient, high throughput, energy saving binder/solubilizer/carrier for hot-melt extrusion and continuous processes with enhanced processability and stability.

¢versatile solid dispersion solubilizer/carrier for enhanced bioavailability in both spray-drying and hot-melt extrusion processes.

¢superior binder for direct compression and dry granulation resulting in hard, non-friable tablets.

Our solvers set out to improve the peroxide stabiltiy and processing ease of original copovidone in HME applications. They successfully created an excipient that has lower peroxide content and growth rate, better powder flowability, extrudates lower in color and improved energy efficiency and throughput.

superior processing efficiencyAs a spray dried powder, Plasdone™ S630 Ultra copovidone is well suited for direct compression, dry granulation, continuous processing and HME. Particles are spherical (Figure 1), with a d50 value of 80 to 160µm and a narrow particle distribution (Figure 2).

figure 1: scanning electronic microscopy of Plasdone™ S630 Ultra copovidone

2

Figure 2: Plasdone™ S630 Ultra particle size and distributon

Figure 3: Flow function and conditioned bulk density of original copovidone and Plasdone™ S630 Ultra copovidone

Figure 4. Processing torque and die pressure of original copovidone and Plasdone™ S630 Ultra copovidone at varied hot-melt extrusion process temperatures

Figure 5: Peroxide growth rate of original copovidone, Plasdone™ S630 Ultra copovidone and a competitor’s copovidone

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The spherical particle morphology of Plasdone™ S630 Ultra copovidone improves powder flow characteristics compared with the original copovidone as indicated in Figure 3. Improved powder flow results in a more efficient manufacturing process and minimizes or eliminates feeder clogging and prevents manufacturing stoppages.

Additionally, Plasdone™ S630 Ultra copovidone has lower melt viscosity(Figure 4) resulting in less energy consumption and better throughput.

greater stabilityMonograph compliant copovidone contains peroxide levels less than 400 ppm. Even at this low level, APIs that are prone to oxidation may experience stability issues and HME extrudates tend to exhibit yellowish discoloration. Plasdone™ S630 Ultra copovidone exhibits significantly lower levels of peroxide (< 100 ppm), mitigating API instability as well as improving extrudate color. In Figure 5, initial levels of peroxide and its growth over a three-week period at ambient temperature is reported for the original copovidone, a competitor’s product and Plasdone™ S630 Ultra copovidone.

As seen in Figures 6 and 7, extrudates prepared with Plasdone™ S630 Ultra copovidone demonstrate a lower yellowness index and significantly lower peroxide levels compared to those prepared with original copovidone at various extrusion temperatures.

Figure 7: Yellowness index and peroxide level of original copovidone and Plasdone™ S630 Ultra copovidone post HME

Figure 8: Plasdone™ S630 Ultra copovidone moisture absorption and desorption profile

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Figure 6. Appearance of original copovidone and Plasdone™ S630 Ultra copovidone post HME

excellent binder for direct compression and dry granulation processesPlasdone™ S630 Ultra copovidone is an excellent binder for direct compression and dry granulation processes (such as roller compaction) because it can be compressed to a higher degree than other polymers. The combination of pyrrolidone and vinyl acetate results in a copolymer with a relatively low Tg and upon compression it undergoes plastic deformation. This results in a slew of benefits starting with higher quality tablets — harder and non-friable — and reduced tablet punch wear due to lower compression forces.

bioavailability enhancementThe unique combination of pyrrolidone and vinyl acetate monomers produces a copolymer with both hydrophilic and hydrophobic properties. This combination is perfect for increasing solubility and ultimately enhancing bioavailability. Plasdone™ S630 Ultra copovidone acts as a solubilizing agent, dispersant, and crystallization inhibitor. When used in spray drying and HME processes, copovidone transforms the API into amorphous nanoparticles or a solid solution. Plasdone™ S630 Ultra copovidone used in solid dispersion formulations prevents recrystallization during storage, facilitates dissolution and inhibits recrystallization in vivo.

tough and flexible filmsFilms made with Plasdone™ S630 Ultra copovidone possess low hygroscopicity, high elasticity, and low tack with a high substantivity to skin. When used in water-based sprays for topical applications, the films are clear and glossy.

monograph statusPlasdone™ S630 Ultra copovidone conforms to the current European Pharmacopeia (EP) and the National Formulary (NF) for copovidone as well as the Japanese Pharmaceutical Excipient standards (JPE) for copolyvidone.

lower hygroscopicity improves stability in high humidityWhen formulating moisture sensitive actives, the low hygroscopicity of Plasdone™ S630 Ultra copovidone makes it an excellent excipient choice. The moisture adsorption profile (Figure 8) indicates that at 50% relative humidity, Plasdone™ S630 Ultra copovidone gains less than 10% moisture.

regional centers

North America Covington, KY USA Tel: +1 859 815 3333

Europe Switzerland Tel: +41 52 560 55 00

India Maharashtra Tel: +91 22 6144646

Asia Pacific Singapore Tel: +65 6775 5366

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 tests and evaluations of the products and their uses. All statements, information and data presented herein are believed to be accurate and reliable, but are not to be taken as a guarantee, an express warranty, or an implied warranty of merchantability or fitness for a particular purpose, or representation, express or implied, for which Ashland and its subsidiaries assume legal responsibility. A purchaser must make its own determination of a product’s suitability for purchaser’s use, the protection of the environment, and the health and safety of its employees and customers. We make no warranty against infringement of any patents by reason of purchaser’s use of any product or formulation described in this document.

Middle East, Africa Istanbul, Turkey Tel: +00 90 216 538 08 00

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