Solubility

ABSTRACTProstate cancer is an androgen-dependent disease that responds to established therapies that reduce circulating testosterone levels or inhibit androgen binding to the androgen receptor. This has resulted in the development of a variety of new drugs that target this hormone-regulated transcription factor. Oral enzalutamide drug is a potent androgen receptor antagonist inhibitor for the treatment of castration-resistant prostate cancer, but enzalutamide is classified as BCS class II substances with low aqueous solubility. In recent decades, dendrimers have proven to be effective as solubilizers. Due to their special qualities, dendritic macromolecule is an effective drug solubilizing agent. Therefor the current work is to improve the solubility of enzalutamide by using hydroxy-terminated dendritic macromolecules. The potential of nanoscale hydroxy-terminated dendritic macromolecules TG1.0, TG2.0 and TG3.0 as enzalutamide solubility enhancers was investigated. The effect of concentration and generation of synthesized dendritic macromolecules on enzalutamide solubility was investigated. The FT-IR spectra were used to characterize the formation of complexes between drug molecules and dendritic macromolecules. The experimental results revealed that enzalutamide solubility increased with dendrimer concentration and generation. The cytotoxicity and hemolytic potential of synthesized hydroxy-terminated dendritic macromolecules excelled over commercially available polyamidoamine dendrimers (PAMAM) in a cytotoxicity assay using A-549 lung cancer cell lines. Keywords: Enzalutamide, Cytotoxicity, Dendrimer, Hemolysis, Solubility

Cyclodextrins are non-toxic cyclic polysaccharides. They form inclusion complexes with numerous organic molecules. The physical and chemical properties of the guest molecules change due to complex formation. Cyclodextrins (CDs) are chemically cyclic oligosaccharides which have been recognized as useful pharmaceutical excipients. Cyclodextrins are versatile pharmaceutical excipients used to enhance the solubility, stability, safety and bioavailability of drug. Besides, being used to reduce gastrointestinal drug irritation, convert liquid drug into microcrystalline or amorphous powder, and prevent drug-drug and drug-excipients interactions. The solubility of slightly soluble molecules may be increased by cyclodextrin inclusion complex. As a result of molecular complexation phenomena cyclodextrins are widely used in many industrial products, technologies and analytical methods.

To describe the solubility related aspects in drug discovery and development with overview on factors affecting solubility of drug along with the special focus on the practical approaches of solubility determination. The solubility is essential factor in the initial stages of drug discovery and development. The determination of solubility gives an idea about the drug response prediction. The poor solubility results in ineffective response in experimental design. The use of solubility data in appropriate setting is very important before screening of drug. The biopharmaceutical classification system is of pH dependent used to classify drugs on the basis of pH dependent solubility and permeability. This article outlines solubility aspects in drug discovery and development with factors that influences solubility and methods to determine the solubility of drug with different models developed to predict solubility.  Investigators are constantly searching for different approaches to determine and predict the solubility of drug. But still there are several work is being done by the investigators to increase the efficiency and accuracy to determine the solubility.