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).
References
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).
|
