Strategies for improving solubility
Both physical and chemical methods can be used to improve drug solubility, Chemical methods to improve solubility include developing more soluble prodrugs or improving solubility through salt formation. Physical methods include micronization or nanosizing, producing a polymorph, changing the crystal habit, complexation, solubilization through self-microemulsifying drug-delivery systems, and solid dispersions (1).The terms solid solution and solid dispersion define related compositions in which at least one active ingredient is dispersed in an inert matrix. In solid dispersions, separate regions of drug and polymer exist throughout the matrix, and the drug may be crystalline or be rendered in its amorphous state. A special subset of solid dispersions, solid solutions, refers to the case in which drug–polymer miscibility is attained at the molecular level, and the drug exists in its amorphous form. Pharmaceutical polymers are used to create this matrix. Polymer selection is based on many factors, including physicochemical (e.g., drug–polymer miscibility and stability) and pharmacokinetic (e.g., rate of absorption) constraints (1, 2).
Solid dispersions may be made through mechanical activation (i.e., cogrinding), coprecipitation, freeze drying, spray drying, melt extrusion, and KinetiSol technology (DisperSol Technologies), a fusion-processing technology. The solid-dispersion components consist of the API, the polymer, plasticizers, stabilizers, and other agents. Various polymers may be used in solid dispersions. These include methylacrylate polymers, polyvinyl acetate, polyvinylpyrrolidone, copovidone, poly-(ethylene-vinylacetate-vinylcaprolatam), and cellulose derivatives (e.g., hypromellose acetate succinate, hydroxypropyl methyl cellulose, hydroxypropyl cellulose, ethyl cellulose, and methyl cellulose) (1).