Nanosuspension
Nanosuspensions are colloidal, solid-liquid systems with a particle size of less than one micrometer. Water , in which the substance is largely insoluble and is incorporated as a particle suspension, is often used as the dispersion medium . Nanosuspensions can also consist of glycerine , oils or other liquid media dispersed nanoparticles made of pure medicinal substance and surfactant without the use of a matrix material.
In medicine, nanosuspensions are of great importance for medicinal substances which are sparingly soluble in water (<5 mg / l solubility) and which, as nanosuspensions, have improved biopharmaceutical properties (e.g. absorption, bioavailability ).
Well-known drugs that are on the market as nanosuspensions are Rapamune ( Sirolimus ) and Prograf ( Tacrolimus ).
Manufacturing
One method for the production of nanoparticles is the precipitation (vhp - via humida paratum) used in DAB 6 for the production of mercury ointments. To produce the so-called hydrosols, the medicinal substance is dissolved in a solvent, the solution is added to a non-solvent and the nanoparticles that form are stabilized by adding surfactants. One difficulty with this technology is the physical stabilization of the nanoparticles and the prevention of the further growth of the crystals into undesired microparticles. The nanosuspension formed is therefore stabilized by subsequent lyophilization . A general problem, however, remains that the active ingredient must be soluble in at least one solvent and this must at the same time be miscible with a non-solvent. This miscibility is often not given. In addition, many of the new sparingly soluble drugs are sparingly soluble in both aqueous and organic media.
An alternative technology for the production of drug nanoparticles is the grinding process developed by Liversidge with a ball or bead mill . The particle dispersion is filled into a container full of grinding balls, which are moved by a stirrer or by moving the grinding container. The drug particles are then ground into nanoparticles between the moving grinding balls. Disadvantages of this process include the long grinding time (up to a week), potential microbiological problems when grinding for several days in an aqueous environment, problems with aseptic production or manufacture of sterile products, and abrasion from the grinding balls. Abrasion is not permitted in a drug (i.e.> 20 ppm), even if the substances in question are essentially non-toxic, such as glass and zirconium oxide, which are used as materials for the grinding media.
Another improved technique is based on the production of nanoparticles in the piston-gap homogenizer. With this technique, the microfine suspension is pressed through a gap (5–50 µm) under high pressure (1500–4000 bar). Shredding takes place through shear and cavitation forces. The main advantages were that the problems of abrasion, particle contamination and the yield of a high proportion of solids in the nanometer range were reduced or avoided with short production times.
See also
Pharmacy , pharmaceutical technology , dosage form
literature
- Scientific literature on nanosuspension on ncbi.nlm.nih.gov
- Deepak Thassu, Michel Deleers, Yashwant Vishnupant Pathak: Nanoparticulate Drug Delivery Systems. CRC Press, Boca Raton 2007 (on Google Books )
- Ron Liu: Water-Insoluble Drug Formulation. Second Edition, CRC Press, Boca Raton 2008, p. 122 f. (on Google Books )
- Bhanu P. Sahu, Malay K. Das: Nanosuspension for enhancement of oral bioavailability of felodipine. In: Applied Nanoscience , February 2014, Volume 4, Issue 2, pp. 189–197, doi : 10.1007 / s13204-012-0188-3
- Vishal R. Patel, YK Agrawal: Nanosuspension: An Approach to Enhance Solubility of Drugs. In: Journal of Advanced Pharmaceutical Technology & Research , April – June 2011; 2 (2): pp. 81-87. PMC 3217698 (free full text)
- Alok K. Kulshreshtha, Onkar N. Singh, G. Michael Wall: Pharmaceutical Suspensions: From Formulation Development to Manufacturing. Springer Science & Business Media, 2009, pp. 17–20 (on Google Books )