Biopharmaceutics and Formulation Development Lecture Notes

Comprehensive vocabulary flashcards covering the fundamentals of biopharmaceutics, pharmacokinetics, drug dissolution kinetics (Noyes-Whitney), crystalline properties, and the Biopharmaceutical Classification System (BCS).

Pharmacodynamics (PD)

The relationship between drug at the site of action and the resulting effect, including the time course and intensity of therapeutic and adverse effects.

Pharmacokinetics (PK)

The study of the mechanisms and the kinetics of Absorption, Distribution, Metabolism and Elimination (ADME), which determines onset, duration, and intensity of effect.

Biopharmaceutics

The study that correlates the physicochemical properties of a drug and its formulation with its availability and bioavailability.

Drug release (availability)

The process where a drug moves from its delivery system (formulated drug) to being in solution (free drug).

Drug adsorption (bioavailability)

Defined as the amount of unaltered drug that reaches the site of action.

Dissolution

The process where drug molecules from the surface layer of a solid pass into solution to form a saturated diffusion layer.

Noyes-Whitney Equation

$\frac{dM}{dt} = \frac{D \times A \times (C_s - C_b)}{h}$ where $\frac{dM}{dt}$ is the dissolution rate, $D$ is the diffusion coefficient, $A$ is surface area, $h$ is diffusion layer thickness, $C_s$ is solubility, and $C_b$ is bulk concentration.

Diffusion coefficient (D)

A factor in the Noyes-Whitney equation that is inversely proportional to molecular size and the viscosity of gastric contents.

Griseofulvin particle size effect

Reducing particle size from $10\,\mu m$ to $2.7\,\mu m$ increases the amount of drug absorbed and intensifies side effects.

Specific surface area

The surface area per unit weight of a powder; increasing it generally increases the dissolution rate and bioavailability for poorly soluble drugs.

Solubility (Cs)

The concentration of a compound's saturated solution in a given solvent at a specific temperature ($T$).

Amorphous form

A physical state where atoms or molecules are arranged randomly; these forms are more readily soluble and absorbed in vivo than crystalline forms.

Novobiocin

A pharmaceutical example where the amorphous form dissolves more readily and reaches higher blood concentrations than the crystalline form.

Polymorphism

The phenomenon where the same compound substance can crystallize in two or more different crystalline forms with distinct physical properties.

Pseudopolymorphism

A phenomenon related to solvates and hydrates; for example, ampicillin hydrates exhibit slower dissolution rates in water than anhydrous forms.

Zinc-insulin complex (Amorphous vs Crystalline)

The amorphous form ($< 2\,\mu m$) has rapid action and short duration, while the crystalline rhombohedral form ($10-40\,\mu m$) has slow absorption and long duration.

Fick's First Law of Diffusion

$\frac{dM}{dt} = \frac{D \times A \times (K_1C_1 - K_2C_2)}{h}$ used to describe passive transport across membranes based on a concentration gradient.

BCS Class 1

High Solubility and High Permeability; examples include Propranolol and Metoprolol.

BCS Class 2

Low Solubility and High Permeability; solubility limits absorption flux and examples include Naproxen and Carbamazepine.

BCS Class 3

High Solubility and Low Permeability; permeability is the rate-determining step and examples include Atenolol and Cimetidine.

BCS Class 4

Low Solubility and Low Permeability; development is considered risky and costly with no IVIVC expected (e.g., Furosemide).

BCS High Solubility Boundary

A drug is highly soluble when the highest dose strength is soluble in $250\,mL$ or less of water over a pH range of $1-7.5$ at $37^\circ C$.

BCS High Permeability Boundary

A drug is highly permeable when the extent of absorption in humans is greater than $90\%$ compared to an intravenous reference dose.

BCS Rapid Dissolution Boundary

A product is rapidly dissolving when $85\%$ or more of the labeled amount dissolves within $30\,min$ in $900\,mL$ or less of buffer.

Dose Number (Do)

$D_0 = \frac{M_0 / V_0}{C_s}$ where $M_0$ is the dose, $V_0$ is $250\,mL$, and $C_s$ is saturation solubility; $D_0 < 1$ indicates high solubility.

Lipinski's Rule of 5

Criteria for oral drug-likeness: $\le 5$ H-bond donors, $\le 10$ H-bond acceptors, $MW < 500\,Da$, and $\log P \le 5$.

Acyclovir drug-likeness

Contains $4$ H-donors, $8$ H-acceptors, $MW$ of $225.21$, and $LogP$ of $-1.56$, thereby passing the Rule of 5 despite poor oral bioavailability.