Short Note on Solubility Enhancement Techniques
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. Most of the drugs are weakly acidic and weakly basic with poor aqueous solubility. Hence various techniques are used for the improvement of the solubility of poorly water-soluble drugs include micronization, chemical modification, pH adjustment, solid dispersion, complexation, co‐solvency, micellar solubilization, hydrotropy etc. The solubility of a drug is represented through various concentration expressions such as parts, percentage, molarity, molality, volume fraction, mole fraction.
pH ADJUSTMENT: Poorly water soluble drugs with parts of the molecule that can be protonated (base) or deprotonated (acid) may potentially be dissolved in water by applying a pH change. pH adjustment can in principle be used for both oral and parenteral administration. Upon intravenous administration the poorly soluble drug may be precipitate because blood is a strong buffer with pH between 7.2 – 7.4. To assess the suitability of the approach, the buffer capacity and tolerability of the selected pH are important to consider. Solubilized excipients that increase environmental pH within a dosage form, such as a tablet or capsule, to a range higher than pKa of weakly-acidic drugs increases the solubility of that drug, those excipients which act as alkalizing agents may increase the solubility of weakly basic drugs.
CO-SOLVENCY: The solubility of a poorly water soluble drug can be increased frequently by the addition of a water miscible solvent in which the drug has good solubility known as cosolvents.17 Co-solvents are mixtures of water and one or more water miscible solvents used to create a solution with enhanced solubility for poorly soluble compounds. Co-solvent formulations of poorly soluble drugs can be administered orally and parenterally. Co-solvents may be combined with other solubilization techniques and pH adjustment to further increase solubility of poorly soluble compounds.
PARTICLE SIZE REDUCTION: The bioavailability intrinsically related to drug particle size. By reducing particle size, increased surface area improves the dissolution properties. Particle size reduction, it is done by milling techniques using jet mill, rotor stator colloid mills etc. Nowadays Particle size reduction can be achieved by micronization and Nano suspension.
Complexation of drugs with Cyclodextrins has been used to enhance aqueous solubility and drug stability. Cyclodextrins of pharmaceutical relevance contain 6, 7 or 8 dextrose molecules (α, β, γ-Cyclodextrins) bound in a 1,4- configuration to form rings of various diameters. HYDROTROPHY: It is a solubilisation process whereby addition of a large amount of second solute results in an increase in the aqueous solubility of another solute. Solute consists of alkali metal salts of various organic acids. Hydrotropic agents are ionic organic salts.
Solubility of the drug is the most important factor that controls the formulation of the drug as well as therapeutic efficacy of the drug, hence the most critical factor in the formulation development. Dissolution of drug is the rate determining step for oral absorption of the poorly water soluble drugs and solubility is also the basic requirement for the formulation and development of different dosage form of different drugs.