Polymorphic drugs: practical aspects of solubility determination

Judith Aronhime, Consultant, Rehovot, Israel (juditharonhime@gmail.com)

Solubility is one of the most important physicochemical properties studied during pharmaceutical pre-formulation of solid dosage forms.   Solubility data are important in determining if an adequate amount of drug is available for absorption in vivo.   For a generic manufacturer solubility data are needed to assess the probability of passing bioequivalence studies.  In drugs in which the dissolution in the gastrointestinal tract is rate-limited or solubility-limited, determination of solubility in physiological pH media is especially meaningful.

Solubility during pre-formulation studies is measured using the saturation shake-flask method.   In this method problems of irreproducibility are frequently encountered.  Solubility is influenced by many variables including temperature, pH, solvent and experimental setting conditions; in addition, the polymorphic form and other solid-state characteristics may severely impact the behaviour of the drug in the liquid medium.   In order to produce reliable and reproducible solubility data the effect of experimental and solid state characteristics need to be understood.  

The importance of understanding the factors that impact solubility data may apply to various aspects of the pharmaceutical business beside pre-formulation studies, like in cases of patent litigations.

The presentation will overview the factors affecting solubility of polymorphic drugs with focus on the practical approaches of solubility determination.

 

 

 

 

 

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Short Biography of Presenting Author

Dr. Judith Aronhime is a consultant in the field of pharmaceutical polymorphism and pharmaceutical solild state science.  She accumulated 27 years experience in her former position in Teva TAPI global R&D management as responsible for all the solid state aspects of the active pharmaceutical ingredients (APIs). In this key role she gained expertise in analysis, characterization, development and research of polymorphism and all solid state attributes of APIs, along with proactive scientific support to patent litigations, prosecutions and clearances.

She was a key contributor to TEVA worldwide leadership position in the intellectual property domain by searching new crystal forms of APIs.  Part of those became API ingredients in the marketed TEVA products.

Author and supervisor to more than 100 patents and current applications.