The low water solubility of pharmacoactive molecules limits their pharmacological potential, but the solubility parameter cannot compromise, and so different approaches are employed to enhance their bioavailability. Pharmaceutically active molecules with low solubility convey a higher risk of failure for drug innovation and development. Pharmacokinetics, pharmacodynamics, and several other parameters, such as drug distribution, protein binding and absorption, are majorly affected by their solubility. Among all pharmaceutical dosage forms, oral dosage forms cover more than 50%, and the drug molecule should be water-soluble. For good therapeutic activity by the drug molecule on the target site, solubility and bioavailability are crucial factors. The pharmaceutical industry’s screening programs identified that around 40% of new chemical entities (NCEs) face various difficulties at the formulation and development stages. These pharmaceuticals demonstrate less solubility and bioavailability. Enhancement of the bioavailability and solubility of drugs is a significant challenge in the area of pharmaceutical formulations. According to the Classification of Biopharmaceutics, Class II and IV drugs (APIs) exhibit poor solubility, lower bioavailability, and less dissolution. Various technologies are discussed in this article to improve the solubility of poorly water-soluble drugs, for example, the complexation of active molecules, the utilization of emulsion formation, micelles, microemulsions, cosolvents, polymeric micelle preparation, particle size reduction technologies, pharmaceutical salts, prodrugs, the solid-state alternation technique, soft gel technology, drug nanocrystals, solid dispersion methods, crystal engineering techniques and nanomorph technology. This review mainly describes several other advanced methodologies for solubility and bioavailability enhancement, such as crystal engineering, micronization, solid dispersions, nano sizing, the use of cyclodextrins, solid lipid nanoparticles, colloidal drug delivery systems and drug conjugates, referring to a number of appropriate research reports.

Rapid gelation, low heat generation, biocompatibility, biodegradability, avoiding the use of a small molecular weight gelator and high gel fraction are the essential criteria for the successful biomedical application of an injectable hydrogel. We have developed a series of dually crosslinked injectable hydrogels of PEG and poly[2-(dimethylamino)ethyl methacrylate]-b-poly(N-isopropyl acrylamide) through extremely simple chemistry. The sequential nucleophilic substitution reaction between PEG containing reactive termini and the copolymer provided chemically crosslinked hydrogels with a gel fraction as high as 96–99% with a gelation time of 1–4 min under physiological conditions. The gelation occurred with ca. 1 °C rise in temperature per gram of the injectable solution, avoids formation of by-products and can be performed in the temperature range of 20–37 °C. The hydrogels undergo hardening at a physiological temperature as confirmed by rheological experiments. The gelation time, water swelling, mechanical properties and degradability of the hydrogels depend on the PEG to copolymer ratio in the injectable solution. The rheological behaviour of the fully hydrated hydrogels showed desirable mechanical properties for soft tissue regeneration. The hydrogels exhibited blood compatibility and retained the viability of HepG2 cells with time. Platelet adhesion and aggregation followed by fibrinogen adsorption ability makes these hydrogels suitable for wound healing applications.