Factors Modifying Bioavailability
Factors Modifying Bioavailability
In all cases, except when a drug is administered intravenously in form of a true solution, the drug has to be released from the dosage form and then be absorbed into systemic circulation by passing through various membranes.
A drug given in different dosage forms or by different routes of administration will yield varying amounts of drug absorbed and, hence, differences in onset, intensity, and duration of the pharmacologic or clinical effect.
In the first case, we call it a physiologically modified bioavailability.
These variations are primarily due to differences in the efficiency and rate of absorption which may originate either with the patient or the dosage form.
In the second case, a dosage form modified bioavailability can occur.
This means that the formulation of the drug itself can impact how much is absorbed, influenced by factors such as particle size, chemical presentation (e.g., salt vs. free base), and the presence of excipients.
In testing bioavailability and bioequivalence, the design of the study protocol must be carefully crafted to exclude physiologically based modifications of bioavailability.
Such factors include age, sex, and physical state of the patient, time of administration, stomach emptying rate, type and amount of food, variations in pH and enzyme action within the gastrointestinal tract, motility of the gastrointestinal tract, blood flow, liver and kidney function, body weight, and psychological factors like stress.
All of these physiological factors can alter the absorption of the drug, thereby complicating the understanding of how a drug performs in different individuals.
Hence, a true cross-over design is often implemented to mitigate these variables through controlled counterbalancing.
The bioavailability or bioequivalence problems specified in the new regulation, therefore, can be attributed to the physico-chemical characteristics of the drug or the dosage form.
Factors that can affect bioavailability include:
Particle Size: Smaller particles may have a larger surface area, leading to increased dissolution rate.
Polymorphic Form: Different crystalline forms of the same substance can have different solubilities and stabilities.
Presence of Solvates or Hydrates: The presence of water or organic solvents in the crystalline structure can impact solubility.
Chemical Presentation: The form in which the drug is presented (e.g., salt, ester, ether) affects its absorption.
pH of Dosage Forms: The acidity or alkalinity can influence the solubility of drugs, particularly weak acids or bases.
Environmental Factors: Temperature and humidity can also affect the stability and solubility of the drug solution.
Solubility Characteristics: A drug must be adequately soluble to be absorbed.
Type and Amount of Vehicle Substances: Excipients utilized in the formulation can facilitate or hinder absorption.
Manufacturing Method: Variability throughout the manufacturing process, such as type of granulation, changes in blending practices, drying conditions, high-speed tablet compression, and compression force adjustments can all lead to inconsistencies in bioavailability.