Solubilizing the Insoluble - Pharmaceutical Technology

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PharmTech Europe

Solubilizing the Insoluble
An analysis of the approaches and tools used to tackle the problem of poorly soluble drugs.

Pharmaceutical Technology
pp. 50-56

Advances from academia

Researchers at the University of Texas at Austin and DisperSol Technologies recently reported on thermal production methods for the production of solid dispersions without the use of plasticizers. Plasticizers are typically needed to achieve the required molten material-flow properties when using unit operations such as hot-melt extrusion. The technology, KinetiSol, a high-energy thermal manufacturing process, was applied to produce amorphous solid dispersions without the aid of a plasticizer. The model active ingredient examined in the study was itraconazole (8).

Poor solubility is particularly problematic when developing anticancer therapeutics because the goal is to achieve clinical efficacy while limiting the dosage of chemotherapeutic agents. To address this issue, researchers at Northwestern University in Evanston, Illinois, recently reported on using nanodiamond-mediated delivery for several water-insoluble drugs. In their study, the researchers reported that nanodiamonds were used to enhance the water dispersion of three anticancer agents: purvalanol A, a treatment for liver cancer; 4-hydroxytamoxifen, a drug to treat breast cancer; and dexamethasone, an antiflammatory agent to treat complications from certain types of cancer (9, 10).

The researchers showed that the water-insoluble compounds interact with the nanodiamonds, a biocompatible material, and formed complexes capable of dispersing the drug in water for sustained periods of time while maintaining the functionality of the drug. The researchers used ultraviolet–visible spectrophotometry, transmission electron microscopy imagery, and zeta potential measurement via dynamic light-scattering analysis to confirm the complexation of the water-insoluble compounds with the nanodiamonds and used methylthiazol tetrazolium and DNA-fragmentation assays to confirm that the functionality of the drugs was maintained (9, 10). Nanodiamonds are a class of nanomaterials 4–6 nm in diameter in single-particle form, which can be manipulated to form clusters with diameters in the range of 50–100 nm, according to the Nanoscale Biotic-Abiotic Systems Engineering Laboratory at Northwestern University. This composition makes them suitable for drug delivery by shielding and slowly releasing drugs that are trapped within the cluster of the diamond aggregates. Benefits in drug delivery from the nanodiamond cluster include the capability of trapping more drug in the nanodiamond cluster compared with conventional drug-delivery methods and facile dissolution of the nanodiamonds in water. Nanodiamond surfaces are functionalized with carboxyl groups to enhance their dispersibility in water. Previous studies showed that the surface electrostatic properties of nanodiamonds can promote potent water binding, thereby further enhancing material dispersibility in water (9, 10).


1. Amdion et al, Pharm Res 12 (3), 413–420, 1995.

2. FDA, Guidance for Industry: Waiver of In Vivo Bioavailability and Bioequivalence Studies for Immediate-Release Solid Oral Dosage Forms Based on a Biopharmaceutics Classification System (Rockville, MD, Aug. 2004).

3. C.Y. Wu and L.Z. Benet et al., Bull. Technique Gattefosse 99, 9–16 (2006).

4. J. Doney and J. Yang, Pharm. Technol. 32 (7), 96–98 (2008).

5. T. Bee and M. Rahman, Pharm. Technol. 34 (9), CPhI/ICSE Supp. s37–s42 (2010).

6. J. Balasubramaniam and T. Bee, Pharm. Technol. 33 (4) Excipient Performance for Solid Dosage Forms Supp., s6–s14 (2009).

7. P. Holm et al., "Controlled Agglomeration," US patent 7217431, May 15, 2007.

8. J.C. DiNunzio et al., Eur. J. Pharm. Sci. 40 (3), 179–187 (2010).

9. P. Van Arnum, Pharm. Technol. 34 (1), 48 (2010)

10. D. Ho, et al., ACS Nano 3 (7), 2016–2022 (2009).


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