High Solubility Research Paper

2.3 SOLUBILITY

2.3.1 Introduction [6]

Drug solubility is the greatest concentration of the drug dissolved in the solvent under specific condition of temperature, pH and pressure. As solubility is an important determinant in drug liberation hence it plays a key function in its bioavailability. For absorption of any drug it must be present in the form of an aqueous solution at the site of absorption. About 40% of all new chemical entities have poor bioavailability. The bioavailability can be increased by changes in disintegration and dissolution. Aqueous solubility smaller than 1μg/ml will definitely create a bioavailability problem and affects the efficacy of the drug.

2.3.2 BCS Classification [7]

Class I High Solubility, High Permeability

In vivo drug dissolution is then a rate limiting step for absorption apart from at a very high dose number. The bioavailability of these products is likely to be dissolution‐rate limited, for this reason, a correlation between in vivo bioavailability and in vitro dissolution rate may be observed.

Class III High Solubility, Low Permeability

In this class for drug absorption permeability is rate limiting step. These drugs show a high variation in the rate and amount of drug absorption. Dissolution will most likely occur very rapidly but absorption is permeability‐rate limited so there has been some proposal that as extended as the test and reference formulations do not contain agents that can modify drug permeability or GI transit time, waiver criteria similar to those associated with Class I compounds may be appropriate.

Class IV Low Solubility, Low Permeability

Those compounds have a poor bioavailability usually they are not well absorbed over the intestinal mucosa and a high variability is expected with very poor oral bioavailability. These compounds are not only difficult to dissolve but once dissolved, often show incomplete permeability across the GI mucosa. These drugs tend to be extremely tricky to formulate and can exhibit very large inter subject and intra subject

The flexibility and precision offered by SCF processes allows micronization of drug particles within narrow ranges of particle size. Under SCF, 2 techniques are used; Solution enhanced dispersion (SEDS) and Rapid expansion from Supercritical to Aqueous Solution (RESAS). SEDS is novel, single step method, which can produce solid drug-cyclodextrin complexes. The optimization of processing conditions is essential in order to achieve the optimum complexation efficiency and to compare with drug cyclodextrin complexation methods, whereas in RESAS, it induces fast nucleation of the supercritical fluid dissolve drugs and surfactants resulting in particle formation with a desirable size distribution in an extremely short