The use of nanocrystals as a tactic for the delivery of poorly soluble drugs
By Dr. Afsaneh Motamed-Khorasani

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One of the major challenges in the field of parenteral drug delivery is the poor solubility of new drugs and their low oral bioavailability, which can cause general delivery problems. It is estimated that more than 40 percent of marketed products are hydrophobic.1 To evaluate the therapeutic index of these drugs and their aptness for technical formulation development, there is a need for good bioavailability.2

INDUSTRY PULSE

Do nanocrystals hold the future for the delivery of poorly soluble drugs?
  • 1. Yes
  • 2. No

Nanocrystal engineering has been discussed in literature as one of the formulation design options for the delivery of poorly soluble drugs. In general, nanocrystals are particles that are purely composed of an active pharmaceutical ingredient without any carrier, which form ultrafine dispersion once in media.2 As mentioned by Shegokar et al., "On administration of a nanocrystal, formulation particles are released in the nanorange, which is of paramount importance in imparting many advantages to the nanocrystals as fast dissolution, increased kinetic saturation solubility and adhesion to biological membranes, which ultimately results in enhanced solubility and permeability."3

Shegokar et al. published a very comprehensive manuscript on nanocrystals in October 2010 with the title "Nanocrystals: Industrially feasible multifunctional formulation technology for poorly soluble actives." According to Shegokar et al., in their article in International Journal of Pharmacology,3 "Nanocrystals being a kind of universal formulation approach for these molecules are reviewed in this paper regarding the industrial feasibility, i.e. industrially available production processes (bottom-up and top-down technologies), regulatory aspects and nanotoxicology.

"This article also includes second generation nanocrystals (<<100 nm) as smartCrystals. The status of products on the market and in clinical phases is presented. The different special features of nanocrystals, which are exploited in different products, are described (tablets, capsule, aqueous nanosuspension). The main focus is given for oral and intravenous products. However, the potential and delivery strategies for other administration routes are discussed, i.e. dermal and mucosal, ocular, pulmonary and targeted delivery (e.g. via differential protein adsorption to the brain). In addition, the potential of the nanocrystal technology for delivery of poorly soluble, nonpharmaceutical actives is highlighted, i.e. in cosmetics or nutraceuticals."

In general, nanocrystals have drawn increasing interest in the pharmaceutical industry due to their ability to improve dissolution of poorly water-soluble drugs. In a review by Sun et al., which was published in December in the Current Opinion in Solid State & Materials Science, different methods of nanocrystal production and their parenteral application have been reviewed in great detail. Furthermore, they have discussed some of the remaining challenges in the development of these products.4

Dr. Afsaneh Motamed-Khorasani is a medical affairs specialist and a senior scientist with a strong background in biomedical sciences and clinical trials. She has a doctorate degree in molecular biology (oncology) from the University of Toronto and many national and international certificates. Dr. Motamed has more than 16 years of experience in the pharmaceutical and medical device industry and is a member of several professional associations. She has published and presented more than 50 peer-reviewed papers, abstracts and articles in highly regarded scientific journals and at many high profile conferences and scientific meetings.

References


1. Giliyar, C, Fikstad, DT, Tyavanagimatt, S. Challenges and oppurtunities in oral delivery of poorly water soluble drugs. Drug Del. Technol. 2006; 6:57-63.

2. Ritika, Harikumar SL, Aggarwal G. Formulation Tactics for the Delivery of Poorly Soluble DrugsInt.J.PharmTech Res.2012,4(3).

3. Shegokar R, Muller RH. Nanocrystals: industrially feasible multifunctional formulation technology for poorly soluble actives. Int J Pharm. 2010 Oct 31;399(1-2):129-39. doi: 10.1016/j.ijpharm.2010.07.044. Epub 2010 Jul 30.

4. Sun B, Yeo Y. Nanocrystals for the parenteral delivery of poorly water-soluble drugs. Curr Opin Solid State Mater Sci. 2012 Dec 1;16(6):295-301.