Solid State Manipulation of Paliperidone for Its Bioavailability Enhancement Using Precipitation Inhibitors

The discovery of new drug molecules, which belongs to BCS class II and class IV, are suffering from poor aqueous solubility related issues. Pharmaceutical scientists are seeking various approaches such as polymorphism, cocrystals, salt formation, etc. to overcome these issues. Among the various methods, modifications of drugs into pharmaceutically useful cocrystals using coformers have been emerged in recent years. This improves the physicochemical properties such as solubility, dissolution, stability, and bioavailability. In addition to this, precipitation inhibitor (PPI) such as hydroxy propyl methyl cellulose (HPMC) can provide a ‘parachute’ effect in biological medium, which further improves the bioavailability of the drug by preventing its precipitation upon the dissociation of cocrystals. Selection of coformers, from the Generally Recognized As Safe (GRAS) list by FDA, can be done by predicting the cocrystal formation using the Hansen solubility parameter (HSP).