ISP offers ingredients and process technology services for the greatest formulation challenge facing the industry today.

It has been estimated that 40-60% of drugs in development have poor bioavailability due to low aqueous solubility.

This percentage is likely to increase in the future with increased use of combinatorial chemistry in drug discovery targeting lipophilic receptors. Poor bioavailability results in increased development times, decreased efficacy, increased inter- and intra-patient variability and side effects, and higher dosages that reduce patient compliance and increase cost.

The ability to improve drug solubility and, hence, bioavailability through formulation and process technology is critical to improving the efficacy and safety of a drug product and to reducing its cost. At ISP, drug solubility is being addressed using the organisation’s expertise in material science and its broad portfolio of ingredients as the foundation for activities ranging from employing traditional formulation technologies to working with emerging ones.

Ingredient technologies

Since no single solution applies to all active pharmaceutical ingredients (APIs), ISP offers a broad range of ingredients that enable the development of poorly soluble drugs (see table). One such solution is Polyplasdone Crospovidone. Studies by ISP have shown that this disintegrant improves the dissolution of poorly soluble drugs in tablet formulations in a way not possible with other disintegrant technologies. Its high surface area combined with unique chemistry result in high interfacial activity and enhanced drug dissolution.

Another option pertains to cyclodextrins. ISP offers a wide range of cyclodextrin products for forming inclusion complexes with poorly soluble drug actives. The resulting cyclodextrin drug complex has improved solubility and thus enhanced drug bioavailability. The company provides cyclodextrins suitable for formulation of solid, liquid and parenteral dosage forms.

Solid experience

Solid dispersions have been gaining momentum as a technology to improve drug solubility and enhance drug bioavailability. They are molecular (thermodynamically stable solid solutions) and/or colloidal (kinetically stable solid suspensions) dispersions of the amorphous API in a polymeric matrix.

While formulations of solid dispersions have been known to improve drug bioavailability since the 1960s, the technology began to receive much greater attention in the late 1990s as a means to address current development challenges.

When properly formulated and processed, the result is a solid dispersion formulation with excellent shelf-life stability. It also has dramatically enhanced drug solubility and bioavailability, which can often be an order of magnitude greater than that of the purely crystalline drug form. Currently, there are five commercial products based on solid dispersion technology.

ISP has years of experience with respect to the formulation of stable solid dispersions with enhanced bioavailability, having worked with over 100 different actives. Its Plasdone K-29/32 Povidone and Plasdone S-630 Copovidone are highly effective polymeric dispersants and stabilising agents used in solid dispersion formulations.

Solid dispersions are most practically and most commonly produced in the laboratory through to commercial scale by either spray-drying or melt-extrusion processes. With many years of spray-drying expertise and a GMP spray-drying facility, the organisation helps to develop solid dispersion formulations from feasibility through clinical supply. In alliance with Coperion in Stuttgart, Germany, a market leader in extrusion equipment, ISP is also working on advancing hot-melt extrusion (HME) technology for the pharmaceuticals market.