Solubility Enhancement

Approximately 40% of the marketed drugs and 70 to 90% of the drugs in development are poorly water soluble. Solubility plays a crucial role in the absorption of the drugs ingested orally. As most of the drugs are poorly soluble the solubility enhancement is the prime requisite to enhance dissolution, bioavailability and therapeutic efficacy. Several approaches as physical modification, pH adjustment, Super critical fluid technology, liquisolid techniques and chemical modifications are to enhance the solubility. Physical methods include particle size reduction, solubility enhancement by carriers, by surfactants, by complexation chemical modifications include Hydrotrophy, co-solvency, nano technology, salt formation and co-crystallization. This review mainly focuses on novel techniques to enhance solubility includes liquisolid system, Spherical agglomeration, melt sonocrystallization, Hydrotrophy, Natural deep eutectic solvents nano technology-based methods, solid state engineering, advanced formulation strategies include self-emulsifying drug delivery systems, and supercritical fluid technology and other innovative techniques like and micro wave assisted techniques.

Compatibility study (based on microenvironmental pH and isothermal stress testing) of Febuxostat was carried out with selected excipients (Microcrystalline cellulose (MCC), Mannitol, Lactose, Hydroxypropyl-β-cyclodextrin (HP-β-CD), Polyethylene glycol(PEG) 6000, Polyvinyl pyrollidoneK30, Eudragit EPO, Sodium starch glycollate, Croscarmellose sodium (CCMC), Sodium lauryl sulphate, Magnesium stearate (MgS), Sodium steryl fumarate, Aerosil 200 and Purified talc) using FTIR and HPLC. Among them, Aerosil 200, MgS, Purified talc, Lactose and MCC were selected for the formulation of Febuxostat tablet. Three different polymers viz. PEG 6000, HP-b-CD and CCMC were selected as independent variables to enhance the dissolution rate by their complexation. Fifteen formulations obtained from Box Behnken design (BBD) (Minitab 16) were prepared through kneading method. Contour plot suggested CCMC (13.01mg) and HP-b-CD (65.45mg) excluding PEG 6000 for optimized formulation. Drug release profile of optimized formulation compared separately with formulation without filler, without polymer, physical mixture and a marketed product using similarity (fs) and dissimilarity (fd) factors showed similarity with marketed product. Similarly, similarity and dissimilarity factors for formulation without filler and optimized formulation was obtained within the range (fs= 82.34 and fd=5.42) indicating that the filler does not have any effect on the drug release. fs and fd for formulation without polymer and physical mixture lied outside the range suggesting the importance of the polymer complexation in the formulation. An accurate, simple, precise and robust reversed-phase liquid chromatographic method was developed for the estimation of Febuxostat. Furthermore, solid state characterization evaluated by FTIR showed that complexation between the polymers has occurred in the optimized formulation.