Industry Perspectives: Achieving Solutions for the Challenge of Poorly Water-Soluble Drugs - Pharmaceutical Technology

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Industry Perspectives: Achieving Solutions for the Challenge of Poorly Water-Soluble Drugs
A multifaceted approach is needed to resolve the myriad of challenges in developing oral formulations of poorly soluble drugs.


Pharmaceutical Technology
Volume 37, Issue 6, pp. 60-62,66

Evaluating the technologies


Figure 3: Importance of factors in choosing a solubilization strategy.
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.

Seeking solutions


Figure 4: Evaluation of strategies/technologies in addressing poor solubility.
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.

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).

Looking ahead

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.

References

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 http://www.PharmTech.com/CatalentSolubility


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