Using Polymer Technology to Enhance Bioavailability - Pharmaceutical Technology

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Using Polymer Technology to Enhance Bioavailability
The authors review seven polymer classes that can be used to prepare solid-dispersion formulations.

Pharmaceutical Technology
pp. s37-s42

Povidone. Povidone is a synthetic linear polymer of 1-vinyl-2-pyrrolidinone groups that contains varying degrees of polymerization that result in polymers with various molecular weights. The different grades of povidone are distinguished by K-value, a measure of specific viscosity which correlates to molecular weight. Commercial grades of povidone range in K-value from K-12 to K-90. Povidone has been used for decades as a dissolution enhancer, suspending agent, and tablet binder. Most commonly, povidone is used as a binder in wet-granulation application. Lower molecular weight povidones such as K-12 and K-17 are regarded as safe for parenteral formulations and as solubility enhancers for liquid-filled soft-gelatin capsules. The K-30 polymer can be used in ophthalmic formulations and all povidones can be used in oral formulations. Povidone is chemically compatible with most organic and inorganic pharmaceutical ingredients (1). For solid-dispersion applications, the 1-vinyl-2-pyrrolidinone group is capable of accepting hydrogen bonds that are stabilized through carbonyl pyrrolidinone groups.

Figure 2: Povidone. (FIGURE IS COURTESY OF ISP)
Povidone also is readily soluble in multiple organic solutions including acetone, dichloromethane, methanol, ethanol, and mixtures thereof, which make it ideal for preparing spray-dried dispersions. Povidone remains chemically and physically stable in various organic solutions for several days. The glass-transition temperatures of povidones increase with increasing molecular weight (120–174 °C /from K-12–K-90). As a result, using melt-extrusion technology without plasticizers makes it difficult to process high molecular weight povidones. In spray-drying applications, however, the high glass-transition temperatures of these polymers aids in producing desired particle size and bulk-density powders with good product yield. One limitation of povidone is its hygroscopicity, which can weaken solid solution stability in humid environments. This challenge can be overcome with proper packaging and storage.

The solubility parameter (δ) of povidone has been calculated using the Hansen method, the van Krevelen and Hoftyzer method, and the Hoy method at 23.1 MPa˝, 22.2 MPa˝, 22.9 MPa˝, respectively (3).

Hypromellose. Hypromellose is a natural cellulose that is synthetically modified to produce partly O-methylated and O-(2-hydroxypropylated) cellulose. It is available in several grades that vary in viscosity and extent of substitution. Hypromellose also has been used for decades as a bio-adhesive material, coating agent, dispersing agent, dissolution enhancer, emulsifying agent, emulsion stabilizer, foaming agent, modified-release agent, solubilizing agent, stabilizing agent, tablet binder, and thickening agent. In oral formulations, hypromellose can be used as a tablet binder for wet- and dry-granulation processes, a film coating agent, and as a matrix in extended-release formulations (1). For solid-dispersion applications, the aliphatic–hydroxyl groups of the natural cellulose and the synthetic 2-hydroxypropoxyl groups are capable of donating hydrogen bond to APIs with hydrogen-bond accepting groups. The synthetic aliphatic methoxyl groups are comparably weak hydrogen-bond acceptors. In most cases, hypromellose is compatible with APIs with hydrogen-bond accepting groups.


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