Pharmacology: Drug Absorption and Stability

The pH-partition hypothesis states that drugs are absorbed passively by diffusing across gastrointestinal epithelia, which acts as a lipid barrier. Only lipid-soluble forms of drugs can pass through. Most drugs are weak electrolytes, existing in both ionized (water-soluble) and unionized (lipid-soluble) forms. Only the unionized, lipid-soluble form can cross the barrier, making the absorption of a drug dependent on its ionization state.

The ionization state of a drug largely determines its absorption. The unionized (lipid-soluble) form can cross the gastrointestinal barrier, while the ionized (water-soluble) form cannot.

It's used to calculate the relative amounts of ionized and unionized forms of a drug at a particular pH. For a weakly acidic drug, the lower the pH, the higher the concentration of the unionized, lipid-soluble form, enhancing absorption.

A drug molecule's ability to dissolve in the fluids of the gastrointestinal tract. A drug must be dissolved in solution to be absorbed.

Drugs can be susceptible to degradation in the digestive tract. Some drugs may undergo hydrolysis, breaking down into inactive forms, thus reducing their effectiveness.

The lipophilicity of a drug is critical in the drug discovery process. Some drugs are poorly absorbed after oral administration even though they are non-ionized in the small intestine. Low lipid solubility of them may be the reason. Polar molecules, i.e. those that are poorly lipid soluble (log P < 0) and relatively large, such as gentamicin, ceftriaxone, heparin and streptokinase, are poorly absorbed after oral administration and therefore have to be given by injection.

The best parameter to correlate between water and lipid solubility is partition coefficient. Partition coefficient (p) = [ L] conc / [W] conc where, [L] conc is the concentration of the drug in lipid phase. [W] conc is the concentration of the drug in aqueous phase. The higher p value, the more absorption is observed.

The process where a solid drug breaks down into smaller particles. It's the first step for a solid drug to be absorbed.

The movement of dissolved drug molecules from the gastrointestinal tract into the bloodstream. This is how the drug reaches the body.

The slowest step in a sequence of steps that determines the overall rate of a process. In drug absorption, it's the step that takes the longest, limiting how quickly the drug reaches the blood.

A model describing drug dissolution, assuming a thin layer of liquid surrounds the drug particle. The drug dissolves and diffuses through this layer.

A model describing drug dissolution, considering that the surface of the drug particle is constantly being renewed. This allows for faster dissolving.

A model describing drug dissolution, where both a stagnant layer and an internal barrier within the drug particle affect the dissolving process.

A model describing drug release where the rate of drug release is constant over time. It’s like an hourglass, releasing sand at a constant rate.

A model describing drug release where the rate of release is proportional to the concentration of the drug remaining in the dosage form. The more there is, the faster it releases.

A model describing drug release from a matrix, based on Fick's law of diffusion. It considers the drug diffusion through the matrix and its solubility.

The rate of drug dissolution is slower when there is food in the stomach because the viscosity of the stomach fluids increases, making it harder for drug molecules to move away from the undissolved drug particles.

Surfactants in the stomach and bile salts can help drugs dissolve better by making the drug molecules more attracted to water and forming smaller groups of molecules called micelles.

Increased stomach and intestinal movement (peristalsis) makes drug molecules dissolve faster because it creates a thinner layer around the drug particles, allowing them to dissolve more quickly.

Fast absorption of drug molecules from the gut and a lot of fluid intake can lead to faster drug dissolution because they reduce the concentration of the drug in the digestive fluids, making it easier for more drug molecules to dissolve.

The smaller the drug particles are, the faster they dissolve because they have a larger surface area exposed to the fluids in the gut.

The drug's ability to dissolve in the fluids around it (its solubility) determines how fast it will dissolve. The more soluble the drug, the faster it dissolves.

Salts of weak acids and bases usually dissolve much better in water than the original acid or base.

The rate of diffusion or movement of drug molecules depends on their size and how thick and sticky the fluid is in the gut. Bigger molecules and thicker fluids slow down diffusion.

Different crystalline forms of a drug. These forms can have different solubility properties, meaning they dissolve at different rates.

A drug exists in this form when it's not organized into a crystal lattice. It dissolves faster than the crystalline form.

A crystalline form of a drug that forms when solvent molecules are incorporated into its structure. Hydrates are a common example.

The process of a weakly acidic salt form drug dissolving in gastric fluid. This is affected by the different pHs of the diffusion layer and gastric fluids.

The pH of the diffusion layer around a drug particle in the stomach. It's usually higher than the bulk pH of gastric fluids because of neutralizing ions.

A form of a drug that is more soluble and thus dissolves faster than the stable form. It's less stable and can transform into the stable form.

Changing the chemical nature of a weakly acidic drug by forming a basic salt (sodium or potassium form) increases the pH of the diffusion layer, leading to faster dissolution.

Drugs can be broken down in the digestive tract by acids or enzymes. This can reduce their effectiveness. Imagine a cookie crumbling before you can eat it.

The rate at which a drug dissolves can vary depending on its form and the pH of the environment. This impacts how quickly and how much of the drug is absorbed.

A drug's tendency to form complexes with other substances in the digestive tract can affect its absorption. Sometimes, it's a good thing, sometimes it's bad.

Enteric coating protects drugs from breaking down in the acidic stomach. It only dissolves in the less acidic small intestine, where absorption is more likely.

Prodrugs are inactive versions of a drug that become active once they reach the small intestine. This allows the drug to reach its target site and absorb properly.

Weak electrolytes like erythromycin can be protected from acidic breakdown in the stomach by using enteric coating or prodrugs.