Drug Nanocrystals

    Lipid Nanoparticles




    Intellectual Property

PharmaSol's Drug Nanocrystals

Drug Nanocrystals
Application areas:
1. increase of oral bioavailability of poorly soluble drugs (drugs of BCS II)
2. creation of supersaturated dermal systems
3. targeted delivery of poorly soluble drugs after intravenous injection
4. pharmacological screening of poorly soluble NCEs

Technology description:

Poorly soluble drugs are transferred to drug nanocrystals via a high pressure homogenisation process. The drug powder is dispersed in a surfactant solution and the forces in the high pressure homogeniser are strong enough to disintegrate the coarse drug powder into drug nanoparticles with a mean diameter typically between 200 nm-600 nm. Dispersion media for the drug nanocrystals are either aqueous media (e.g. water-ethanol mixtures, isotonic water-glycerol mixtures) or non-aqueous media leading to suspensions suitable for direct filling of capsules for oral administration.
The homogenisation production lines are already used in the pharmaceutical industry (e.g. for the production of parenteral emulsions), which means that they are regulatorily acceptable. Production lines already available in industry can be used for the production. Excipients used possess an accepted status (e.g. FDA approved, GRAS).

Advantages over competing technologies:

Drug nanocrystals can also be produced by pearl/ball milling. Disadvantages of this method are potential contamination of the product by erosion of the milling material, relatively long milling times for hard crystalline drugs, and limited scaling up due to the weight of large scale pearl mills.
Drug nanocrystals can also be produced using pure water as a dispersion medium. The water mixtures used by PharmaSol are advantageous for some purposes (e.g. spray-drying). Non-aqueous dispersion media, such as PEG or oils, yield suspensions that are suitable for the direct filling of capsules and thus an intermediate step required when using pure aqueous nanosuspensions is avoided.

Large scale production/costs:

Large scale production is easily achieved because high pressure homogenisation is a technology applied in the pharmaceutical industry for the production of parenteral emulsions. The batch sizes are 1 ton of dispersion or more. Even larger batch sizes are produced in the food industry using homogenisation. The equipment is off the shelf equipment and is of relatively low cost. The excipients used for nanoparticle production are also low cost substances and generally have excipent regulatory status.

IP position:

For an overview of patents and patent applications please click "Intellectual property".

For a short overview please read :

Article 1    Article 2

Further Information regarding this topic can be obtained by reading:

Müller, R. H., Jacobs, C., Kayser, O., Nanosuspensions as particulate drug formulations in therapy - Rationale for Development and what we can expect for the future, in: Advanced Drug Delivery Reviews (ADDR) 47, 3-19, 2001

Jacobs, C., Müller, R. H., Production and characterizatoin of a budesonide nanosuspension for pulmonary administration, Pharmaceutical Research 19 (2), 189-194, 2002

Müller, R. H., Jacobs, C., Buparvaquone mucoadhesive nanosuspensions: Preparation, optimisation and long-term stability, Int. J. Pharm. 237, 151-161 (2002)

Müller, R. H., Nanopure technology for the production of drug nanocrystals and polymeric particles, 4th World Meeting ADRITELF/APV/APGI, Florence, 769-770, 2002

Krause, K., Rogaschewski, S., Niehus, H., Müller, R. H., DirectCompress: a matrix-excipient compound for direct compression of prolonged release tabletts with high polymer content, 4th World Meeting ADRITELF/APV/APGI, Florence, 271.272, 2002

Müller, R. H., Akkar, A., Industrial production of Nanopure drug nanocrystal dispersions, Intern. Symp. Control. Rel. Bioact. Mater. 30, #293, 2003

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