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Questions and Answers
What is the term used for the rate of transfer of molecules from a solid state into a homogeneous dispersion?
What is the term used for the rate of transfer of molecules from a solid state into a homogeneous dispersion?
Increased surface area always decreases the rate of solution.
Increased surface area always decreases the rate of solution.
False
What is the Noyes-Whitney equation primarily used to describe?
What is the Noyes-Whitney equation primarily used to describe?
Dissolution process
The step that often limits the rate and extent of absorption in dissolution is known as _______.
The step that often limits the rate and extent of absorption in dissolution is known as _______.
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Match the following factors with their impact on dissolution rates:
Match the following factors with their impact on dissolution rates:
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Which factor does NOT influence the saturation solubility (Cs) in the dissolution process?
Which factor does NOT influence the saturation solubility (Cs) in the dissolution process?
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Cohesion is the force that attracts different molecules, while adhesion is the force that attracts similar molecules.
Cohesion is the force that attracts different molecules, while adhesion is the force that attracts similar molecules.
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Name two types of dosage forms that require dissolution for drug absorption.
Name two types of dosage forms that require dissolution for drug absorption.
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What is the typical characteristic of drugs with water solubility of less than 0.01mg/mL?
What is the typical characteristic of drugs with water solubility of less than 0.01mg/mL?
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Sink conditions occur when the solute is removed from the dissolution environment at a slower rate than it's dissolved.
Sink conditions occur when the solute is removed from the dissolution environment at a slower rate than it's dissolved.
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What is defined as rapid dissolution for a dosage form in terms of percentage and time?
What is defined as rapid dissolution for a dosage form in terms of percentage and time?
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The _____ layer thickness can impact the rate of drug dissolution.
The _____ layer thickness can impact the rate of drug dissolution.
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Match the physiological factors to their influence on in vivo dissolution of tablet dosage forms:
Match the physiological factors to their influence on in vivo dissolution of tablet dosage forms:
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What does the Noyes-Whitney equation assume about dissolving particles?
What does the Noyes-Whitney equation assume about dissolving particles?
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The viscosity of a dissolution medium has no impact on the rate of drug absorption.
The viscosity of a dissolution medium has no impact on the rate of drug absorption.
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List one physicochemical factor that influences in vivo dissolution of oral dosage forms.
List one physicochemical factor that influences in vivo dissolution of oral dosage forms.
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Study Notes
Dissolution
- Dissolution is a crucial process for drug absorption.
- Solid dosage forms (tablets, capsules) must dissolve before the drug can be absorbed.
- Suspensions, which are incompletely dissolved, also require dissolution.
- Dissolution is critical for drug absorption, efficacy, and safety.
Learning Outcomes
- Explain the dissolution process.
- Describe dissolution factors using the Noyes-Whitney equation.
- Discuss physiological, physicochemical, and formulation factors influencing dissolution.
- Describe how diffusion affects dissolution (controlled release).
Dissolution of Solids
- Solid dosage forms disintegrate into granules.
- Granules or aggregates deaggregate into fine particles.
- Particles dissolve releasing the drug for absorption in the body.
- Dissolution happens in vitro (in the lab) or in vivo (inside the body).
Dissolution (Rate of Solution)
- Intrinsic dissolution rate is the molecule/ion transfer rate from solid state to homogenous dispersion.
- Measured in units of time and surface area.
- Factors include interfacial reaction and migration.
Dissolution: Interfacial Reaction
- Solute removal from crystals.
- Creation of a cavity in the solvent.
- Cavity insertion to hold the solute molecule.
- Cohesion and adhesion affect interaction.
Dissolution: Migration
- Dissolved molecules move from the boundary layer into bulk solution.
- Diffusion occurs in a solvent layer around undissolved particles.
- A rate-limiting step for absorption.
Mathematics of Dissolution
- Dissolution is governed by the Noyes–Whitney equation.
- dm/dt = k1A(Cs - C)/h
- dm/dt: rate of dissolution.
- k1: diffusion coefficient.
- A: surface area of the solid.
- Cs: saturation solubility.
- C: concentration of solute.
- h: thickness of the boundary layer.
Factors Influencing Dissolution Rates of Solids in Liquids
- Surface area (A): Increased surface area increases the rate of solution (↑ A ↑ rate of solution).
- Saturation solubility (Cs): Increased saturation solubility increases the rate of solution (↑ Cs ↑ rate of solution).
- Solute concentration (C): decreased solute concentration in solution increases the rate of solution (↓ C ↑ rate of solution).
- Diffusion coefficient (K₁): increased diffusion coefficient increases the rate of solution (↑ K₁ ↑ rate of solution).
- Thickness of boundary layer (h): decreased thickness of the boundary layer increases the rate of solution (↓ h ↑ rate of solution).
- Other factors: particle size, disintegration, porosity, temperature, medium properties, molecular structure, crystalline form, other compounds, volume, removal of the drug (absorption), viscosity, temperature, molecular diameter, agitation.
Dissolution and Drug Absorption
- Drugs with low water solubility (< 0.01 mg/mL) have dissolution rate-limited absorption.
- Rapid dissolution (>85% dissolution in 30 minutes in 900 mL medium at 37°C) is important.
- Many factors affect drug absorption (influencing efficacy and safety).
Dissolution and Sink Conditions
- Rate of removal of solute from the environment affects dissolution.
- Faster removal than solution (e.g., C < 10% Cs) means sink conditions.
Kinetics of Dissolution
- Zero-order dissolution (under sink conditions) is linear.
- First-order dissolution (non-sink conditions) increases in rate with time.
Limitations of Noyes–Whitney Equation
- Assumes dissolving particles remain constant throughout dissolution (not true for tablets, capsules, and suspensions).
- Limited to zero-order release.
Physiological Factors Influencing in Vivo Dissolution
- GI fluid volume and co-administered fluids.
- Fasted/fed state.
- Surfactant concentration and micelle diffusivity.
- Residence time and mixing (motility patterns).
- Disease state.
- Diet (e.g., alcohol, other medicines).
Fluid Volume Available for Dissolution in the GI Tract
- Oral cavity: 0.9-1.1 mL
- Stomach: 118 mL
- Small intestine: 212 mL
- Large intestine: 187 mL
- Rectum: 2-3 mL
Physicochemical Factors Influencing In Vivo Dissolution
- Solubility (Log P).
- Melting point.
- Physical form (salt, hydrate, solvate, crystalline or amorphous).
- pKa.
- Molecular weight (MW).
- Particle size.
- Physical behavior (rheological properties).
- Wettability.
Formulation Factors Influencing in Vivo Dissolution
- Dosage form (tablet, capsule, suspension, emulsion).
- Particle size (processing).
- Release properties (IR, SR, DR, CR).
- Excipient composition (surfactants, binders, lubricants, disintegrants, solubility enhancers, granulating agents).
In Vitro Dissolution Testing
- Predicts in vivo dosage form behavior.
- Used in new innovator products and bioequivalence testing.
- Important for regulatory approval and manufacturing quality control.
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Description
This quiz explores the critical process of dissolution in drug absorption, focusing on solid dosage forms, suspensions, and factors affecting dissolution rates. Students will learn to explain the dissolution process and its impact on drug efficacy and safety, using key equations and physiological factors. Test your understanding of both in vitro and in vivo dissolution.
