What does kinetic solubility mean?
The kinetic solubility of a compound is the maximum solubility of the fastest precipitating species of the compound; this is often measured using a stock solution of the compound dissolved in an organic solvent, typically dimethyl sulfoxide (DMSO), as the starting material.
What is polymorphism in drug substance?
Polymorphism occurs when a chemical compound crystallizes with different internal structures. ICH Q6A defines polymorphism as “some new drug substances exist in different crystalline forms which differ in their physical properties. In many known cases, several polymorphs crystallize concomitantly.
What are Enantiotropic polymorphs?
An enantiotrope is a polymorph that undergoes a reversible transformation into another polymorph at atmospheric pressure. If you’re not familiar with the concept of reversibility you may want to read up on entropy, spontaneity, and the 2nd law of thermodynamics.
What is meant by intrinsic solubility?
The intrinsic solubility is the solubility of the compound in its. free acid or free base form.4. A supersaturated solution is one in which the concentration of dissolved neutral species is greater than the intrinsic solubility. This is not at equilibrium and may or may not have solid precipitate present.
What does apparent solubility mean?
Apparent Solubility. Defined in USP <1236> The empirically determined solubility of a solute in a solvent system. The apparent solubility may be either higher or lower than the equilibrium solubility due to transient supersaturation or incomplete dissolution and insufficient time to reach equilibrium.
How does polymorphism affect solubility?
In conclusion, decreasing solubility and dissolution will reduce the bioavailability and these two factors are related to polymorphism. According to Byrn “the stable form is also the least soluble form” which means that the thermodynamically stable form is not always bioavailable.
Is paracetamol Monotropic and Enantiotropic?
In the present article, it has been found that one of the polymorphs of metacetamol is only stable under increased pressure, which has led to the conclusion that metacetamol like paracetamol is a monotropic system under ordinary (= laboratory) conditions and that it becomes enantiotropic under pressure with the I-II-L …
What is Enantiotropic system?
The term enantiotropic refers to a phenomenon where one polymorph is stable over one temperature range while another polymorph is stable over a different temperature range. Enantiotropic substances are polymorphic substances having two or more polymorphic states that have their stabilities at specific temperatures.
What is Enantiotropic transition?
For enantiotropic polymorphs, the transition temperature is of great importance since it defines the temperature at which the stability relationship between the two forms becomes inverted. The transition temperature is the temperature at which the two forms have the same solubility.
What is meant by solubilization?
Solubilization is the formation of a thermodynamically stable, isotropic solution of a substance (the solubilizate), normally insoluble or slightly soluble in water, by the addition of a surfactant (the solublizer).
How do you find intrinsic solubility?
The method involves titrating a basic compound from high to low pH, or an acidic compound from low to high pH, and calculating the apparent ionization constant from the pH of each point in the full titration curve. The intrinsic solubility is calculated from the shift compared to the aqueous ionization constant.