Drug release

Active ingredient release describes the release of an active ingredient from its formulation . The release of the active ingredient and the dissolution of the active ingredient are prerequisites for its absorption .

Release of active ingredient after oral application

In order to achieve absorption of the active ingredient from the intestinal lumen into the bloodstream and ultimately to the site of action, it must first be released from the drug form and present in dissolved form.

The drug form, usually a tablet, can either dissolve directly in the intestine or, as a depot drug form, only convert into a solution after further processes in the form of granules or fine powder. The active ingredient is in a chemical equilibrium between the dissolved active ingredient and the bound and / or complexed active ingredient; in the bloodstream this is the plasma protein bond . A dissolved active ingredient is efficiently absorbed and released into the bloodstream.

In addition to pharmacokinetic studies, there are established in-vitro tests to investigate the release of active substances. The in vitro tests are u. a. carried out for quality control of various factors. They are used to monitor the effects on the release of the active ingredient in a drug form, due to changes in the physical or chemical properties of the active ingredient due to auxiliary substances or due to changes in the drug formulation, especially in the pre-formulation phase.

For the quality controls during batch production, investigations into the release of active ingredients are carried out to ensure batch uniformity. Furthermore, results from the in vitro tests can be used to predict the release in vivo.

Speed of resolution

The speed of solution describes the course of the solution process over time. This is of great importance for the drug formulation because it represents the rate-determining step for the resorption process in many poorly soluble drugs. Important factors that can influence the speed of solution can be derived from the Noyes-Whitney equation . The Noyes-Whitney equation describes the diffusion-related dissolution rate of drug particles from the drug form.

${\ displaystyle {{\ mathrm {d} Mt} \ over {\ mathrm {d} t}} = {\ frac {A * D * (C_ {s} -C)} {\ delta}}}$

d Mt / d t = amount of active ingredient that goes from the dosage form into solution per unit of time

A = total surface area of the drug particles

D = diffusion coefficient of the drug in the dissolution medium

δ = thickness of the hydrodynamic boundary layer

C _s = solubility of the drug in the dissolution medium

C = dissolved drug concentration of the drug in the dissolution medium

The resolution can be influenced by the surface or the physicochemical parameters such as particle size, shape and wettability of the particle. The diffusion coefficient of the drug depends on its molar mass and the viscosity of the solvent . The hydrodynamic boundary layer, on the other hand, can be influenced by hydrodynamics such as the stirring speed. Furthermore, the solubility of the drug depends on the substance properties and also on the solvent.

It follows that the rate of dissolution according to the Noyes-Whitney equation can be changed by changing these parameters.

Factors influencing drug release

The release of the active ingredient can be influenced by various factors. These include the properties of the drug, the quality and design of the dosage form and the test conditions for the in vitro test (dissolution test). The properties of the drug include solubility in the medium, lipophilicity or hydrophilicity , particle size, crystallinity, polymorphism in the drug form and the salt form . The quality and design of the dosage form includes the various dosage forms, such as immediate release (immediate release), modified release (changed release), delayed release (delayed release), extended release (prolonged release), the manufacturing parameters, the dose and the properties of the Auxiliary materials.

The conditions of the dissolution test include the classification of the active ingredient according to solubility, the appropriate selection of the medium according to composition and volume, the selection of the device according to the type of drug and hydrodynamic aspects such as stirring speed / flow rate / diprate.

Active ingredient release in the pharmacopoeia

In some pharmacopoeias , official dissolution test systems are declared, e.g. in United States Pharmacopeia USP XXXIX, European Pharmacopoeia Ph. Eur. 8th Edition, International Pharmacopoeia .

In the pharmacopoeia, various apparatuses for the analysis of active ingredient release are described, such as App.1: rotating basket apparatus, apparatus 2: blade stirrer apparatus, apparatus 3: immersing cylinder, apparatus 4: flow cell, active ingredient release from chewing gum containing active ingredients.

literature

Alfred Fahr : Voigt Pharmaceutical Technology - For studies and work; 12th edition; ISBN 978-3-7692-6194-3 .
Kurt H. Bauer, Karl-Heinz Frömming, Claus Führer: Textbook of Pharmaceutical Technology - With an Introduction to Biopharmacy; 9th edition; ISBN 978-3-8047-2552-2 .
Ph.Eur. 8th edition, basic work 2014