Augmenting Excipient Functionality - Pharmaceutical Technology

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PharmTech Europe

Augmenting Excipient Functionality

Pharmaceutical Technology
Volume 34, Issue 7, pp. 48-52

Technology challenges

Excipient manufacturers must continually adapt their products and technology to resolve problems in formulation development. Water solubility presents an ongoing challenge. Industry figures estimate that approximately 40% of the drugs on the market and nearly 60% of drugs in development may be classified as poorly water-soluble. Drug–polymer solid solutions and solid dispersions are approaches that can be used to address the problem of drug solubility (2).

In both a solid solution and solid dispersion, at least one active ingredient is dispersed in an inert matrix. In solid dispersions, separate regions of drug and polymer are in the matrix, and the drug may be crystalline or it may be in an amorphous state (2). A solid solution exists when the drug–polymer miscibility is attained at the molecular level, and the drug exists in its amorphous form (2).

Formulation development forum: on-demand drug delivery
Pharmaceutical polymers are used to create this matrix. Commonly used polymers include polyvinylpyrrolidones, polyvinylpyrrolidone-vinyl acetate copolymer, and cellulosics (2). Polymer selection is based on physicochemical and pharmacokinetic factors. These solid solution/dispersions can be produced by many methods, including spray drying, hot-melt extrusion, melt congelation, spray freezing into liquid, and nanocrystal technology (2). Some examples of commercial drugs using solid solutions/solid dispersions are: solid solutions of lopinavir and ritonavir in a polyvinylpyrrolidone-vinyl acetate copolymer in Kaletra (Abbott Laboratories, Abbott Park, IL); Sporanox (Janssen Pharmaceutica, Titusville, NJ), a solid dispersion of itraconazole in hypromellose that has been layered onto sugar spheres; and Intelence (Tibotec, Yardley, PA), an amorphous, spray-dried solid dispersion of etravirine, hypromellose, and microcrystalline cellulose (2).

Several excipient manufacturers recently launched services and products to tackle the problem of poorly water-soluble drugs. In October 2009, International Specialty Products (ISP, Wayne, NJ) launched an initiative in drug-solubility and formed an alliance for hot-melt extrusion technology with Coperion (Stuttgart, Germany), an equipment manufacturer, including extruders. Coperion is providing equipment for testing and expertise in physical systems that use extrusion. ISP is providing expertise in ingredient technology such as polymers and disintegrants. The alliance is focusing on ways to improve scale-up of these processes for commercial production.

Hot-melt extrusion technology features combinations of drugs, polymers, and plasticizers into various final forms to achieve designated drug-release profiles, according to ISP. Individual components are mixed and processed in a controlled environment of temperature and shear within the extruder to create the final material. Hot-melt extrusion is used to prepare granules, sustained-release tablets, and transdermal and transmucosal drug-delivery systems. Some potential benefits include fewer processing steps, no requirements on the compressibility of the drug actives, more uniform dispersion of the drug particles, and improved bioavailability of poorly soluble drug actives.

In October 2009, ISP expanded its research and development (R&D) facilities in Hyderabad, India, to create a Solubility Center of Excellence as part of its drug-solubility initiative. The facilities in Hyderabad serve as a focal point for the R&D for the solubilization of drug actives and focus on the use of polymers, disintegrants, and cyclodextrin chemistry as tools to achieve improved drug solubility and bioavailability in oral and parenteral pharmaceuticals. The center also focuses on solid-dispersion technology for drug formulation, including spray drying and hot-melt extrusion applications.

CSR and sustainability forum
Other excipient producers also are focusing on applications in hot-melt extrusion. In October 2009, BASF (Ludwigshafen, Germany) launched an excipient (Soluplus), a solubilizer for hot-melt extrusion applications. Evonik (Essen, Germany) is also applying its expertise in pharmaceutical polymers in pharmaceutical melt extrusion technology. For example, in 2008 the company formed a partnership with Thermo Fisher Scientific (Waltham, MA) under which Thermo is providing equipment and Evonik expertise in polymer chemistry and ingredients for hot-melt extrusion.


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