Almost 40% of the new chemical entities at present self find out poorly water soluble drugs. Badly water soluble drugs have solubility and dissolution related bioavailability problems. Solubility is one of the most important parameter to give desired concentration of drug in systemic circulation to get its pharmacological response. Orally administered drugs obtained completely absorb only when they show fair solubility in gastric medium and such drugs shows good bioavailability. The solubility and dissolution properties of drugs perform an valuable role in the process of formulation development. Enhancement of solubility of drug is the most challenging job in drug development process. Solubilization may be affected by co solvent water interaction, micellar solubilization, reduction in particle size, inclusion complexes, solid dispersion, and change in polymorph. This review highlight various techniques of solubility enhancement with special emphasis on Chemical modification methods like Salt formation, Co-crystallization, Co-solvency, Hydrotropy, use of novel solubilizer etc along with physical modification techniques. Keywords: Salt formation, Co-crystallization, Solubility, particle technologies, Milling solubility enhancement, Cosolvent, physical and chemical methods.

A series of nonsteroidal "dissociated" glucocorticoid receptor agonists was optimized for drug-like properties such as cytochrome P450 inhibition, metabolic stability, aqueous solubility, and hERG ion channel inhibition. This effort culminated in the identification of the clinical candidate compound ( R )-39.

The objective of this study was to assess the feasibility and reliability of using miniaturized disk dissolution apparatus for intrinsic dissolution rate (IDR) measurement in the early drug discovery process when bulk drug supply is very limited. The two apparatus, a miniaturized rotating disk system (mRDS) and a miniaturized stationary disk system (mSDS), were evaluated using chloramphenicol as a model drug with sample sizes of 3-10 mg. Wood's rotating disk system (wRDS) was used as control with a sample size of 150 mg.The effect of various experimental parameters on IDR was studied on the two miniaturized apparatus. While compression force, disk distance, dissolution volume, and drug loading did not have significant effects on IDR measured by mRDS, dissolution volume and disk distance showed significant effects by mSDS. When all experimental parameters were held constant, the stationary system generated significantly higher IDRs compared with the two rotating systems (mRDS and wRDS). The mRDS yielded IDR values comparable to those by wRDS at 25 rpm (a slower rotation speed).These study results indicate that both miniaturized systems produce reliable IDR measurements with a small quantity of material, which provides a desirable advantage over other methods (e.g., wRDS, solubility measurement) in the early drug discovery phase.

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Introduction:The majority of drugs obtained through synthesis and development show poor aqueous solubility and dissolution velocity, resulting in reduced bioavailability of drugs. Most of these problems arise from formulation-related performance issues, and an efficient way to overcome these obstacles and to increase dissolution velocity is to reduce the particle size of drug substances to form drug nanosuspensions.Materials and Methods:Danazol nanosuspensions were prepared by wet milling (WM) and high-pressure homogenization (HPH) methods. The nanosuspensions obtained using these fabrication methods were analyzed for their particle size, surface charge, and the crystallinity of the product was assessed by X-ray diffraction (XRD) and differential scanning calorimetry techniques. To determine in vitro and in vivo performances of the prepared nanosuspensions, dissolution velocity, and bioavailability studies were performed.Results:Particle size and zeta potential analysis showed the formation of nanosized particles with a negative charge on the surface. XRD depicted the nanocrystalline nature of danazol with low diffraction intensities. With increased surface area and saturation solubility, the nanosuspensions showed enhanced dissolution velocity and oral bioavailability in rats when compared to the bulk danazol suspension.Conclusions:The results suggest that the preparation of nanosuspensions by WM or HPH is a promising approach to formulate new drugs or to reformulate existing drugs with poorly water-soluble properties.