Amorphization is the scientists' way to improve the effectiveness of drugs
The main challenge modern pharmacology is facing is the issue of accelerating and improving the effects of tablets by increasing their solubility, says Prof. Marian Paluch from the University of Silesia. The solution are the so-called amorphic drugs.
Prof. Paluch from the Department of Biophysics and Molecular Physics of the University of Silesia has been dealing with amorphous pharmaceuticals for over a decade. "More than 35 percent of the currently available medicinal substances are characterized by low bioavailability due to the poor solubility of these drugs. It is estimated that more than 70 percent of new compounds with the greatest potential to become pharmaceuticals, will be rejected during the research and development process precisely because of their poor water solubility" - he explained in an interview with PAP.
This concerns drugs in a solid form - tablets, pellets or capsules. One of the more effective methods that can improve the bioavailability of active substances they contain is to convert them into so-called amorphous form. Amorphous bodies combine some of the properties of solids and liquids - the substance in the amorphous state is a solid, but the molecules that form it are arranged in a chaotic manner, more like a liquid.
"In solid forms, active substances are present in the crystalline form, their molecules are ordered, they form the so-called crystalline lattice. Their solubility can be improved by converting them to a chaotic, amorphous form, also called glassy, in which the molecules do not form a lattice, but are arranged in a chaotic manner" - added Prof. Paluch.
Amorphous systems have higher internal energy than their crystalline equivalents; this is due to the absence of this internal "long range" order. As a result, less energy is needed to dissolve these substances, so amorphization leads to increased solubility.
Crystalline medicinal substances can be converted into amorphous form by various methods. According to Prof. Paluch, the simplest method is melting the crystalline form, followed by rapid cooling; this allows to avoid the pharmaceutical reverting to its original, crystalline form.
This method, however, is not always effective, also due to the fact that some substances have a melting point close to the sample degradation temperature (and the compound that degrades before cooling can not be administered to the patient). Another way to amorphize is to grind the active substance at low temperatures; this method allows to mechanically break the internal order of the pharmaceutical, leading to its amorphization.
"The problem begins after the above transformation, because the disordered form is physically unstable. This means that the substances in this form can return to their original crystalline form, losing their wonderful properties. The described effect of recrystallization of amorphous materials can be compared to honey, which tends to crystallize over time. Research on amorphous pharmaceuticals focuses on determining the time of their physical stability and keeping them in disorder as long as possible. We have to be sure that the drug will not lose its properties throughout its shelf life - three years" - said the physicist.
The latter issue - maintaining the amorphous form for a long time - is now the biggest reseach challenge for Prof. Paluch.
The scientist estimates that the interest in the so-called amorphous drugs in the world is significant. A proof are scientific conferences devoted to this topic, in which Prof. Paluch regularly participates.
However, the professor emphasized that it would be impossible to market amorphous drugs without the cooperation of physicists, chemists and pharmacists. "The entire process requires cooperation - from the idea, the way to amorphize the substance, through studying factors that determine physical stability, finding a way to stabilize this form - to studies of the pharmaceutical properties, solubility, release rate, etc." - he explained. He added that the introduction of these drugs is not a far-sighted prospect, but funds are needed.
Prof. Paluch\'s team already has several patents and patent applications in this area. "We are pioneers in the country and we have a very good recognition in the world" - said the researcher. A year ago, the team received a PLN 5 million grant for their research from the National Science Centre.
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