Abstract
The intensive efforts undertaken to get effective drugs have resulted in the generation of candidates with unfavorable properties, i.e., greater lipophilicity, high molecular weight resulting in poor aqueous solubility. It was reported that more than 40% of the drugs discovered belong to the Biopharmaceutics Classification System Class II and IV drugs, i.e., have low aqueous solubility, poor dissolution, and low bioavailability. Thus, it can be stated that drug solubility and bioavailability enhancement approaches are the important challenges in facing the pharmaceutical scientists. In this chapter, we have discussed many methods to uplift the drug solubility which includes pH modification, crystal structure manipulation which includes polymorphs, salt formation, cocrystal, complexation, crystal structure disruption (amorphization), supersaturated solutions, prodrug strategies, size reduction, and excipient-based solubilization which includes cosolvency, polymer as excipient, surfactant as excipient, lipid, and cyclodextrin. Overall, this chapter provides the summary of the strategies which may be used to report the challenges of low solubility during drug discovery.
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