PharmaSol's Drug Nanocrystals
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
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.
For an overview of patents and patent applications please click "Intellectual property".
For a short overview please read :
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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