Dissolution Solutions Network

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Dissolution Theory

Theory

Drug Absorption from a solid oral dosage depends on the release of the drug substance from the drug product (dissolution), the solubility, and the permeability across the gastrointestinal tract. The first aspect of the tablets is determined by the manufacture of the product. The next two aspects are determined by the properties of the active pharmaceutical. All solid oral dosage forms can be characterized according to these three properties.

 

Biopharmaceutics Classification System

A scientific framework for classifying drug substances based on their aqueous solubility and intestinal permeability. When combined with the dissolution of the drug product, the BCS takes into account three major factors that govern the rate and extent of drug absorption from IR solid oral dosage forms: dissolution, solubility, and intestinal permeability. According to the BCS, drug substances are classified as follows:

Class 1: High Solubility – High Permeability

Class 2: Low Solubility – High Permeability

Class 3: High Solubility – Low Permeability

Class 4: Low Solubility – Low Permeability

In addition, IR solid oral dosage forms are categorized as having rapid or slow dissolution. Within this framework, when certain criteria are met, the BCS can be used as a drug development tool to help sponsors justify requests for biowaivers

 

Dissolution Profiles

dissolution profile stages

The ideal immediate release profile goes through 5 main stages. These are my suggestions for appropriate names. While many of these actions are occurring through out the profile, these named are the primary factor affecting the shape of the profile. The fourth name is borrowed from astronomy. It is a term used to describe the diminishing light of a star as a celestial body slowly blocks it from view. The fifth term is a borrowed medical term used to describe the complete blockage of an artery, no longer able to deliver any more blood.
A: Disintegration
B: Deaggegation
C: Release
D: Occultation
E: Occlusion

 

Dissolution Profiling

Dissolution profile of two products (12 units each) of the test and reference products.

To use the mean dissolution values from both curves, the percent coefficient of variation at the earlier time points should not be more than 20% and at other time points should not be more than 10%.

Only one measurement should be considered after 85% dissolution of both of the products.

The dissolution measurements of the test and reference batches should be made under exactly the same conditions.

Dissolution& Particle Size

In order for a drug to have its effect after oral administration it must go into solution and then diffuse through the gut wall into the body. The first step in that process is the disintegration of the dosage form followed by dissolution of the active ingredient. Dissolution of a pure substance follows the Noyes Whitney Equation. dc/dt = kS (Cs- Ct) where dc/dt is the rate of dissolution, k is the dissolution rate constant, S is the surface area of the dissolving solid, Cs is the saturation concentration of drug in the diffusion layer and Ct is the concentration of drug in dissolution media (or the bulk). One way to increase dissolution rate of poorly soluble drugs is to increase the surface available for dissolution. This is done by reducing particle size or by dividing the dosage form into two smaller tablets or capsules, with a larger combined surface area. Other ways include increasing the disintegration rate and deaggregation.

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