Solubility enhancement

Silymarin, a hepatoprotective agent has poor aqueous solubility and high permeability [class II drug]. Its absorption is dissolution rate limited. In order to improve the dissolution profile of silymarin solubility enhancement techniques were employed. Among the various techniques, solid dispersions were employed due to its feasibility. Polymers used were HPMC and PEG. Silymarin was formulated by kneading method and solvent evaporation method, where HPMC and PEG were used in different ratios of drug: polymer. Polymer characterization for the prepared solid dispersion was done using FT-IR, XRPD, SEM and DSC. In vitro dissolution studies were carried out in 0.1M HCl and phosphate buffer mixed (pH 6.8). From the in vitro studies, dissolution efficiency and drug release kinetics was also calculated. FT-IR studies revealed that there was no interaction between the drug and the polymers used. DSC, XRPD and SEM supported the existence of silymarin in amorphous state, in the prepared solid dispersions. Drug content analysis showed maximum drug release of 101.03 for solid dispersion prepared using drug: HPMC in the ratio of 1:3 [KM2] using polysorbate 80, employing kneading method. In vitro release of KM2 was found to be 98.87 ± 0.32 in 0.1 M HCl buffer.  Kneading method proved to be superior to solvent evaporation method. Compared to the pure drug silymarin, solid dispersions [KM2] gave a 2.2 fold increase in the dissolution profile.

Solid dispersion of Oxcarbazepine (OXC) was prepared by hot melt extrusion of OXC with hydrophilic polymer. The main objective was to explore the potential of Hot Melt Extrusion technique (HME) as an industrial scalable green technique for the preparation of solid dispersion and therefore enhancement of dissolution of poorly soluble drug. Polymer for extrusion was selected on the basis of solubility parameters and glass transition (Tg). OXC solid dispersion was prepared using Kollidon VA 64 and Soluplus as hydrophilic carrier. OXC and polymer was mixed in different ratio and extrudates were evaluated for appearance, DSC, PXRD, flow property and dissolution characteristics. DSC and PXRD studies revealed the significant reduction in crystallinity of OXC. OXC-kollidon VA 64 extrudates have good flow property having angle of repose 29° and carr’s index 11.2 and good compressibility with hardness 5-6 kg/cm2. Particle size of extrudates exhibited significant effect on disintegration time and dissolution. OXC release was found to be complete within 45 min from tablets of OXC hot melt extrudates while plain OXC showed just 39 % release. Solid dispersion of OXC was successfully developed using HME technology followed by formulating it into directly compressible tablets.

Solubility is the phenomenon of dissolution of solid in liquid phase to give a homogenous system. Solubility is one of the important parameter to achieve desired concentration of drug in systemic circulation for pharmacological response to be shown. Poorly water soluble drugs often require high doses in order to reach therapeutic plasma concentrations after oral administration. Low aqueous solubility is the major problem encountered with formulation development of new chemical entities. Any drug to be absorbed must be present in the form of an aqueous solution at the site of absorption. The ability to increase aqueous solubility can thus be a valuable aid to increasing efficiency and/or reducing side effects for certain drugs. This is true for parenterally, topically and orally administered solutions. The solubility of drugs is defined according to (bio-pharmaceutical classification system) BCS classification system which divides drugs to different class according to its solubility. Solid dispersion is defined as dispersion of one or more active ingredients in an inert carrier or matrix known as solid dispersion. Solid dispersion reduces the particle size and changes the micro environment of the drug particle, increases the rate of dissolution and absorption and thus changes the biopharmaceutical properties of poorly water soluble drugs. The solid dispersion method, by which a drug is dispersed in a carrier to make it amorphous, is one of the pharmaceutical approaches most commonly employed to enhance bioavailability of poorly water soluble drugs. Various pharmaceutical approaches for the preparation of SDs, including co-precipitation, lyophilization, spray drying, solvent evaporation, fusion and powder mixing methods, have been reported. It’s a new and efficient technique to improve the solubility of poorly soluble drugs.