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Polymorphism of Active Pharmaceutical Ingredients – The border between a real quality issue and an effective patent tool


*Corresponding Author
1. Dipharma Francis Srl, Via Bissone 5, 20021, Baranzate (Milan), Italy
2. Dipartimento di Scienza e Alta Tecnologia, Università dell’Insubria, via Valleggio 11, 22100, Como (Italy)


Polymorphism is considered crucial in the pharmaceutical industry for the potential influence that solid-state can have on the quality, safety and efficacy of the final drug product. In particular, great emphasis is put on the effect that polymorphism can have on bioavailability. As a matter of fact, this influence is limited only to some specific cases, as suggested by the scientific and patent literature on the subject. Other aspects like variations in stability, hygroscopicity or crystal habit, can be issues as well, However, the key factor in determining the importance of Polymorphism in the pharmaceutical industry is the fact that crystal forms are patentable. This can be a very effective tool because it gives the opportunity to obtain IP rights on inventions even when there are no true advantages


Polymorphism, the ability of a substance to exist in more than one crystal form, has grown in importance in the pharmaceutical industry over the last few years. The increasing attention dedicated to the solid state of APIs is due to the fact that the crystal structure of a compound can influence many properties like solubility, hygroscopicity, chemical stability, etc. Many formulations like pills and tablets contain the active ingredient in solid form, so if the crystal form of the API in the formulated final product is not always the same, some safety and efficacy issues could arise. For instance, if the formulated polymorph is different from the one previously used, it could have a reduced solubility which, in the same tablet composition, could lead to a reduced bioavailability of the same active ingredient which compromises the efficacy.
However, even though bioavailability is an important issue, a drastic change of bioavailability from one polymorph to another is not as common as expected. Other issues could be related to the formulation process: stability, hygroscopicity and flowability, are related to the crystalline form and ...