Evaluating the technologies
Given the complexity of formulation challenges when working with poorly soluble drugs, the survey examined the importance
of factors in deciding on a solubilization strategy. The physiochemical properties of the API and safety were both major factors
(see Figure 3). Interestingly, the depth and availability of expertise, including third-party expertise, were significant factors. Ninety-three
percent of respondents said that internal expertise and knowledge were "very important" or "somewhat important," and access
to third-party expertise and knowledge were commensurately important (see Figure 3). More than half (53%) said bioavailability and solubility issues were a reason to partner.
Figure 3: Importance of factors in choosing a solubilization strategy.
The survey also asked respondents to evaluate solubilization/bioavailability enhancement strategies (see Figure 4). "Enhancing bioavailability is multifactorial and involves approaches to optimize the API, the formulation, and the processing
technology to develop the final product form," explains Nielsen. "These factors are codependent and synergistic in most cases,
so a 'best-in-class' toolkit for solubility enhancement includes multiple technologies," he adds. For example, a solubilization
approach may first address salt formation and excipient selection. Other technologies, such as particle milling/micronization,
nanoparticles, spray-drying, hot-melt extrusion, liquid-filled capsules, and softgels, can be further evaluated for suitability
for a given formulation challenge.
Figure 4: Evaluation of strategies/technologies in addressing poor solubility.
Ralph Lipp, PhD, head of Lipp Life Sciences, member of the advisory board of the Catalent Applied Drug Delivery Institute,
and formerly vice-president of pharmaceutical sciences R&D at Eli Lilly, offered several examples of commercial drugs to illustrate
the diversity of solubility/bioavailability enhancement strategies (3). The HIV treatment Kaletra (ritonavir and lopinavir)
uses solid dispersions produced by hot-melt extrusion, and the antifungal drug Sporanox (itraconazole) is produced as a solid
dispersion by spray-drying. The antinausea drug Emend (aprepitant) uses particle engineering (i.e., nanocrystals/media milling)
to improve bioavailability. And the protease inhibitor Fortovase (saquinavir) is formulated in a self-emulsifying drug-delivery
system in a softgel capsule (3).
These advances in solubility and bioavailability enhancement are an integral part of meeting the needs of patients for efficacious
drugs. "Several essential medicines based on advanced oral drug-delivery technologies provide significant value to patients
around the globe today already," says Lipp. "In light of the current trend toward low solubility and poor bioavailability
drug candidates in the pipelines of innovators, this class of technologies is of increasing relevance. Formulation scientists
applying proven and novel oral drug-delivery technologies will significantly contribute to enabling the next generation of
important medicines," concludes Lipp.
1. A. Fahr and D. Douroumous, "Preface" in Drug Delivery Strategies for Poorly Water Soluble Compounds, A. Fahr and D. Douroumous, Eds. (John Wiley & Sons, Chichester, UK, 2013), p xxiii.
2. P. Van Arnum, Pharm. Technol. 36 (4), 128-131 (2012).
3. R. Lipp, "The Innovator Pipeline: Bioavailability Challenges," presented at DCAT Week, Mar. 14, 2013.
Editorial podcast: strategies for bioavailability enhancement
Kurt Nielsen, PhD, chief technology officer and senior vice-president of R&D at Catalent Pharma Solutions, discusses solubilization
strategies and bioavailability enhancement with Pharmaceutical Technology Executive Editor Patricia Van Arnum. Listen to the podcast at