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Welcome to Activery
Activery is a drug delivery specialized in the research, development and production of new drug delivery systems and novel crystal forms. Activery’s expertise and technology can be used to address the following major challenges in the pharmaceutical industry:
- Generation of new solid states for Life Cicle Management and Patent strategy for important drugs or blockbusters (products with sales exceeding 1 billion $)
- Solubility enhancement of very poorly soluble drugs or insoluble drugs as they are the majority of current API (Activer Pharmaceutical Ingredients) and new chemical entities(NCE)
- Enabling of new routes of administration to create more convenient ways of treating the pacients.
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Amorphization: obtaining stable amorphous forms
Nowadays combinatorial chemistry is routinely used as method of choice for the discovery of new drugs. Despite its successes the technique frequently optimizes lead molecules which are poorly or completely insoluble in aqueous media.  This insolubility causes low total bioavailability and poses a significant challenge to formulators. Overcoming the solubility challenge has opened possibilities for new solid-state forms with enhanced solubility. Thermodynamically, the amorphous state shows the greatest solubility advantage, however it has also the largest propensity to revert to other, less soluble solid-state forms on storage. Further, the lack of a crystal lattice can cause increased degradation or even expose new parts of a molecule to chemical attack leading to additional stability storage problems.
A challange for the pharmaceutical industry
Preventing the transition into thermodynamically more stable forms is still a major challenge. Amorphous forms of pure drugs are often unstable and recrystallize easily. This problem is exacerbated with mixtures of drugs, which also have the possibility to demix in the solid state. In addition, not only one but several different amorphous states (by X-ray crystallography) can be envisaged, from microcrystalline composites to solid-state solutions in which all components are randomly distributed in a molecular dispersion.
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The past: Micronization and milling for particle reduction
Particle size reduction is frequently the first choice to improve an existing active ingredient. For inhalation, micronization is often employed. These techniques are often classified as ‘top-down’ methods as they involve the comminution of larger particles into smaller ones. Historically, jet-milling has been used extensively in the pharmaceutical industry to provide acceptable particles for different inhaler types. Despite the wealth of knowledge and numerous applications of ‘top-down’ techniques, several important issues, such as crystallinity, solid-state and batch-to-batch consistency regarding particle size and distribution are still a major concern.
Generation of nanoparticles is commonly attempted through extended ball milling or emulsion techniques. Milling as a typical ‘top-down’ technique usually results in highly energetic particles which necessitate a high surfactant and stabilizer loading to prevent irreversible aggregation or recrystallization of amorphous domains. Similarly, emulsion processes, although ‘bottom-up’ techniques, use large quantities of surfactants to produce the emulsion and are largely unable to generate a dry powder advantageous for long term storage.
Challenges in particle size reductionProviding suitable microparticles with the right particle size and distribution for inhalation is still a major challenge. Jet-milling frequently generates a substantial amount of fines in the powder, while simultaneously a fraction of the powder is only incompletely milled, leading to lower fine particle fractions (FPF) making larger doses necessary. Further, milling often introduces static electricity onto the powder making them cohesive leading to handling problems and potentially to lower emitted doses (ED) from the device. |
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