BIOPHAR - Biopharmaceutic Classification System (BCS)

BIOPHARMACEUTICS CLASSIFICATION SYSTEM (BCS)

• is a scientific framework used to classify drug substances based on two important properties: aqueous solubility and intestinal permeability
• by considering these properties in combination with the dissolution of the drug product, it helps assess the rate and extent of drug absorption from IR solid oral dosage forms

DISSOLUTION

• refers to the PROCESS of a drug dissolving and becoming available for absorption in a biological system
• influenced by factors such as the drug's formulation, particle size, and other physicochemical properties

SOLUBILITY

refers to the ability of a drug substance to dissolve in a liquid typically water

HIGH SOLUBILITY

means that a drug can readily dissolve

LOW SOLUBILITY

indicates that the drug has limited ability to dissolve

INTESTINAL PERMEABILITY

refers to how easily a drug can cross the intestinal membrane and enter systemic circulation

HIGH PERMEABILITY

means that a drug can efficiently pas through the intestinal wall

LOW PERMEABILITY

drug faces challenges in cross the barrier

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-VITRO IN-VIVO CORRELATION

• correlates in vitro drug dissolution with in vivo bioavailability (Amidon et al, 1995)
• provides a framework for understanding how drug dissolution and permeation through the GI tract impact the availability of a drug in the body
• plays a crucial role in establishing a relationship between in vitro dissolution testing and in vivo performance (help estimate the drug's behavior in the human body based on its dissolution characteristics)

LEVEL A

= highest level of correlation

• direct relationship between in vitro dissolution and in vivo performance
• allows dissolution testing to be used as a surrogate for in vivo bioequivalence studies reducing the need for extensive human testing

LEVEL B

• partial correlation where dissolution data can predict the rank order of different drug products' in vivo performance
• still valuable in providing information about the relative performance of different formulaitons

LEVEL C

• indicates a correlation between dissolution and in vivo performance but without accurate prediction of the rate or extent of drug absorption
• may not provide precise quantitative predictions

GENERIC DRUG DEVELOPMENT

IVIVC is particularly important during _, where bioequivalence must be demonstrated compared to the reference (brand-name) drug [can use dissolution testing as a surrogate for expensive and time-consuming clinical trials]

SOLUBILITY

helps determine the amount of drug that can dissolve in a given solvent under approximate physiological conditions

pH-SOLUBILITY PROFILING

it is recommended to conduct _ over a pH range of 1 to 8 to determine the equilibrium solubility of a drug

PERMEABILITY

• it refers to the ability of a drug to cross biological membranes, particularly the intestinal membrane, and be absorbed into the bloodstream

GRATER THAN 90%

• drug is highly permeable
• majority of the drug is effectively absorbed into the bloodstream after oral administration

IN VIVO INTESTINAL PERFUSION STUDIES IN HUMANS

these studies involve administering the drug to human subjects and directly measuring its absorption in the intestines using techniques such as collecting intestinal fluid or urine samples

IN VIVO OR IN SITU INTESTINAL PERFUSION STUDIES IN ANIMALS

similar to the human studies, these experiments are conducted in animal models, allowing for the assessment of drug absorption and permeability

IN VITRO PERMEATION EXPERIMENTS USING EXCISED HUMAN OR ANIMAL INTESTINAL TISSUES

this method involves obtaining intestinal tissues from humans or animals and measuring the drug's permeation across these tissues in a controlled laboratory setting

IN VITRO PERMEATION EXPERIMENTS ACROSS A MONOLAYER OF CULTURED HUMAN INTESTINAL CELLS

this approach involves growing a later of human intestinal cells on a permeable membrane and measuring the drug's ability to permeate through the cell layer

DISSOLUTION

• important parameter in evaluating the behavior of IR drug products
• refers to the process of a drug substance dissolving and becoming available for absorption in a biological system
• objective is to assess the rate at which the drug product dissolves in a simulated physiological environment and to correlate it with the average rate of gastric emptying in humans under fasting conditions

BIOPHARMACEUTICS DRUG DISPOSITION CLASSIFICATION SYSTEM (BDDCS)

takes into account drug metabolism (drug clearance) and transporters in the GI tract for drugs that are orally administered

DISINTEGRATION

• refers to the breaking down of the tablet into small particles and releasing the drug
• COMPLETE _ as the state where any residues on the test apparatus screen, except for insoluble coating fragments, have no palpably firm core (USP-NF)

BIORELEVANT DISSOLUTION TESTING

• aims to stimulate the conditions inside the body where the majority of the drug is released from the formulation
• factors: pH conditions, contents of the GI tract (enzymes and other substances), volume of the GI tract, transit time, dosing conditions

APPARATUS 1

• this apparatus consists of a basket that is placed in a cylindrical vessel containing the dissolution medium
• it rotates at a constant speed, and the dosage form is held in the basket by friction
• recommended for dosage forms that are small and relatively uniform in size, such as tablets and capsules

APPARATUS 2

• this apparatus consists of a paddle that is placed in a cylindrical vessel containing the dissolution medium
• it rotates at a constant speed and the dosage form if free to move within the vessel
• recommended for dosage forms that are larger or more irregular in size (modified-release tablets and capsules)

APPARATUS 3

• consists of a cylinder that is placed in a water bath
• the cylinder reciprocates (moves back and forth) at a constant speed, and the dosage form is free to move within the cylinder
• recommended for dosage forms that are highly cohesive or that tend to float, such as extended-release tablets and capsules

APPARATUS 4

• consists of a cell that is connected to a pump (forces the dissolution medium through the cell, and the dosage form is placed in the cell)
• recommended for dosage forms that are highly soluble or that dissolve rapidly, such as immediate-release tablets and capsules

APPARATUS 5

• similar to apparatus 2 (but the paddle is placed over a disc)
• the disc helps to disperse the dosage form in the dissolution medium
• recommended for dosage forms that are small and relatively uniform in size, such as tablets and capsules

APPARATUS 6

• consists of a cylinder that rotates within a water bath
• the dosage form is placed in the cylinder and the dissolution medium is circulated around the cylinder
• recommended for dosage forms that are highly cohesive or that tend to float, such as extended release tablets and capsules

APPRATUS 7

• similar to apparatus 3, but the cylinder is replaced by a disc (helps to disperse the dosage form in the dissolution medium)
• recommended for dosage forms that are small and relatively uniform in size, such as tablets and capsules