BIOPHARMCEUTICAL

• Bioequivalence


  Two medicinal products are considered bioequivalent if they are pharmaceutically equivalent or pharmaceutical alternatives and their bioavailability after administration in the same molar dose are similar to such degree that their effects, with respect to both efficacy and safety, will be essentially the same
• Pharmaceutical equivalence


  Medicinal products are pharmaceutically equivalent if they contain the same amount of the same active substance(s) in the same dosage forms that meet the same or comparable standards
• Pharmaceutical equivalence does not necessarily imply bioequivalence as differences in the excipients and/or the manufacturing process can lead to faster or slower dissolution and/or absorption
• Pharmaceutical equivalents


  Pharmaceutically equivalent drug products are designed to contain the identical amount of active ingredient in the same dosage form and adhere to the same or compendial standards or other relevant criteria concerning strength, quality, purity, and identity
• Pharmaceutical equivalents may differ in characteristics such as shape, scoring pattern, release mechanisms, packaging, excipients (including color, flavor, preservatives), expiration date, and, to some extent, labeling
• When applicable, pharmaceutical equivalents must satisfy the same requirements for content uniformity, disintegration times, and/or dissolution rates
• Pharmaceutical alternatives


  Medicinal products are pharmaceutical alternatives if they contain the same active moiety but differ in chemical form (salt, ester) of that moiety or in the dosage form or strength
• Variations in dosage forms and strengths within a product line by a single manufacturer also fall under the category of pharmaceutical alternatives, such as an extended-release form and a standard immediate-release form of the same active ingredient
• Bioavailability


  Rate and extent to which the active substance or active moiety is absorbed from a pharmaceutical form and becomes available at the site of action
• Methods for assessing bioavailability

  • Plasma drug concentration
  • Urinary drug excretion
  • Clinical observations
  • In-vitro studies

  
• Plasma drug concentration


  • Time for peak plasma (blood) concentration (Tmax)
  • Peak plasma drug concentration (Cmax)
  • Area under the plasma drug concentration-time curve (AUC)

  
• Urinary drug excretion


  • Cumulative amount of drug excreted in the urine (Du)
  • Rate of drug excretion in the urine (dDu/dt)
  • Time for maximum urinary excretion (t)
• Biopharmaceutics Classification System (BCS)


  A scientific model used to categorize drug substances according to their solubility in water and permeability in the intestines
• BCS classes


  • Class 1: High solubility, High permeability
  • Class 2: Low solubility, High permeability
  • Class 3: High solubility, Low permeability
  • Class 4: Low solubility, Low permeability
• Factors modifying bioavailability


  • Route of administration
  • Drug formulation
  • First-pass metabolism
  • GI motility and pH
  • Food and drug interactions
• Increased gastric emptying time (GET)

  HASUL (Hypothermia, Antidiarrheals, Sleeping at the left side, Ulcers, Low GER)
• Decreased gastric emptying time

  Strenuous activity, Mild activity, Prokinetics (metoclopramide), Sleeping at the right side
• Weak acid drug


  Absorb in acidic environment, Excrete in basic environment
• Weak base drug


  Absorb in basic environment, Excrete in acidic environment
• Increased dose


  Increased rate of absorption
• Increased surface area


  Increased rate of absorption
• Increased perfusion


  Increased rate of absorption
• Strenuous exercise after meals

  Lower blood flow to digestive track, Higher blood flow to exercising muscles
• Relative bioavailability


  Compares the bioavailability of a drug product to that of a reference product, typically expressed as a ratio of the areas under the plasma concentration-time curve (AUC) or peak plasma concentrations (Cmax) of the test product to those of the reference product

  
• Absolute bioavailability


  Measures the extent of systemic drug exposure (bioavailability) of a drug after administration via a specific route, typically compared to intravenous administration
• Absolute bioavailability represents the fraction of the administered dose that reaches systemic circulation unchanged
• Evaluation of bioavailability studies

  • Plasma drug concentration
  • Single dose studies

  
• Plasma is most commonly used for drug measurement, assuming the drug concentration in the plasma is in equilibrium with the tissues

  
• Bioavailability


  The fraction of an administered dose of a drug that reaches systemic circulation unchanged after administration via a specific route, typically compared to intravenous administration
• Absolute bioavailability is often expressed as a percentage and provides valuable information on the efficiency of drug absorption and potential factors affecting it
• Plasma Drug Concentration


  • Plasma is most commonly used for drug measurement
  • Assuming the drug concentration in the plasma is in equilibrium with the tissues
  • Data is generated by obtaining the drug concentration in plasma samples taken at various time intervals after a drug product is administered
  • The concentration of drug in each plasma sample is plotted on rectangular-coordinate graph paper against the corresponding time at which the plasma sample was removed

  
• Evaluation of Bioavailability Studies

  1. Dosing

  2. Sampling of Pre-determined time intervals

  3. Bio-analytics

  4. Concentration vs. Time profiles

  
• Peak Plasma Concentration (Cmax)

  The point of maximum concentration of drug in plasma

  
• Time of Peak Concentration (tmax)

  The time for drug to reach peak concentration in plasma (after extravascular administration)

  
• Area Under the Curve (AUC)


  It represents the total integrated area under the plasma level-time profile and expresses the total amount of drug that comes into the systemic circulation after its administration

  
• Minimum Effective Concentration (MEC)


  The minimum concentration of drug in plasma required to produce the therapeutic effect

  
• Maximum Safe Concentration (MSC)

  The concentration of drug in plasma above which adverse or unwanted effects are precipitated

  
• Onset of Action


  The beginning of pharmacological response
• Onset of Time


  The time required for the drug to start producing pharmacological response
• Duration of Action


  The time period for which the plasma concentration of drug remains above the MEC level