This document summarizes key concepts related to diffusion, dissolution, and pharmacokinetic parameters. It defines diffusion as the spontaneous migration of molecules from high to low concentration regions driven by Brownian motion. Fick's laws describe the rate of diffusion being proportional to the concentration gradient. Dissolution is defined as a solid solute dissolving in a solvent to form a solution. Several parameters influence dissolution rate including surface area, diffusion coefficient, and concentration gradient. Pharmacokinetics describes the absorption, distribution, metabolism, and excretion of drugs and key parameters include Cmax, Tmax, and AUC which describe the concentration of drugs in plasma over time.

1. PRESENTED BY :
ANANYA S
1ST M PHARM
PHARMACEUTICS
NGSMIPS
DIFFUSION, DISSOLUTION AND
PHARMACOKINETIC PARAMETERS

2. CONTENTS
• Introduction to diffusion
• Diffusion parameters
• Introduction to dissolution
• Dissolution parameters
• Introduction to pharmacokinetics
• Pharmacokinetic parameters
• Conclusion
• References
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3. DIFFUSION
• Diffusion is the spontaneous migration of molecules from a region of high concentration to a
region of lower concentration and is result of the Brownian movement of the solute
molecule until the concentration is uniform throughout the system.
• The driving force for diffusion is usually the concentration gradient.
• Diffusion is observed during the release of the drug (from the dosage form), absorption
(across GIT or skin), distribution (into tissue),and even excretion (through kidney).
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4. • Fick’s first and second law is useful for observing the magnitude of diffusion or
permeability. Higuchi equation is routinely used for evaluating the drug release
by diffusion mechanism.
Fick’s law:
• It states that the drug molecules diffuse from a region of higher concentration to
one of lower concentration until equilibrium is attained.
• Rate of diffusion is directly proportional to the concentration gradient across
the membrane.
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5. • It is expressed as flux(J). equal to the rate of mass transfer across a unit surface area of a
barrier.
• 𝐽 = −𝐷
𝑑𝐶
𝑑𝑥
− −(2)
Where,
dC = change in concentration of material
D = diffusion coefficient of a penetrant
dx = change in distance
• D, may change in its value with high concentration.
• D is affected by temperature, pressure, solvent properties and chemical nature of diffusant.
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6. Higuchi equation
• Equation indicates that the amount of drug released is a function of the square root to time.
𝑀 = 𝑘𝑡½
where k is a constant.
• A plot of amount of drug released versus square root of time will be linear, if the release of
drug from the matrix is diffusion controlled .
• This is known as Higuchi model or diffusion model
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7. Diffusion parameters:
• The rate of drug transfer is directly proportional to the concentration gradient between GI
fluids and the blood compartment.
• Greater the area and lesser the thickness of the membrane, faster the diffusion; thus, more
rapid is the rate of drug absorption from the intestine than from the stomach.
• Greater the membrane/water partition coefficient of drug, faster the absorption; since the
membrane is lipiodal in nature, a lipophilic drug diffuses at a faster rate by solubilising in the
lipid layer of the membrane.
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8. • The drug diffuses rapidly when the volume of GI fluid is low; conversely, dilution of
GI fluids decreases the drug concentration in these fluids (𝐶𝐺𝐼𝑇 ) and lower the
concentration gradient (𝐶𝐺𝐼𝑇 -C).
• The diffusion generally decreases with increase in the molecular weight of the
compound. Drugs having molecular weights between 100 – 400 Da are effectively
absorbed passively
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9. DISSOLUTION
• Dissolution is a process by which solid solute dissolve in a solvent to yield a solution.
• A drug is released from solid dosage form and immediately go into molecular solution.
• Rate of dissolution is the amount of drug substance that goes in in solution per unit time
under standardized condition.
Dissolution process can be explained well by Noye’s – Whitney’s equation:
Where,
𝑑𝐶
𝑑𝑡
= 𝑘(𝐶𝑠 − 𝐶𝑏)
dC/dt= dissolution rate of the drug
k= dissolution rate constant
𝐶𝑠= concentration of the drug in the saturated layer
𝐶𝑏= concentration of the drug in the bulk of the solution at time t.
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10. 10

11. The Fick's first law of diffusion was included and modified the Noyes-Whitney's equation to:
𝑑𝑐
𝑑𝑡
=
𝐷𝐴𝐾𝑤/𝑜(𝐶𝑠 − 𝐶𝑏)
𝑉 × ℎ
−−−− −(1)
D = diffusion coefficient (diffusivity) of the drug
A = surface area of the dissolving solid
Kw/o = water/oil partition coefficient of the drug, considering the fact that dissolution body
fluids are aqueous.
V = volume of dissolution medium.
h = thickness of the stagnant layer.
(Cs-Cb) = concentration gradient for diffusion of drug.
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12. PARAMETERS SYMBOL INFLUENCE ON DRUG DISSOLUTION
Diffusion coefficient of
drug
D Greater the value, faster the dissolution.
Diffusion decreases as the viscosity of
dissolution medium increases
Surface area of solid drug A Greater the surface area, faster the dissolution;
can be increased by micronization of drug.
Water/oil partition
coefficient of drug
Kw/o Higher the value, more the hydrophilicity and
faster the dissolution in aqueous fluids.
Concentration gradient (Cs-Cb) Greater the concentration gradient, faster the
diffusion and drug dissolution; can be
increased by increasing drug solubility and the
volume of dissolution medium
Thickness of stagnant
Layer
h More the thickness, lesser the diffusion and
drug dissolution
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13. • Higher the value of KW/O the greater is the hydrophilicity and faster will be the
dissolution in aqueous fluids.
• The value of KW/O is nothing to do with the absorption of drug through biological
membrane.
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14. Effect of agitation:
• The relationship between the intensity of agitation and the rate of dissolution varies
considerably according to the type of agitation used, degree of laminar and turbulent
flow in the system, the shape and design of the stirrer and the physicochemical properties
of the solid.
• Dissolution test using high speed agitation may lack discriminative value and can yield
misleading results.
• For basket method, 100rpm usually is utilised, while for the paddle procedure, 50-75rpm
is recommended.
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15. Influence of pH of dissolution fluid:
• Changes in the pH exert the greatest effect in terms of drug solubility. Most of the drug are
weak electrolyte their degree of ionization mainly depends upon the pH of the biological
fluid.
• For weak acids, the dissolution rate increases with increasing pH whereas, for weak bases,
the dissolution rate increases with decreasing pH. Example: acetylsalicylic acid (pKa=3.5)
tablets and capsules, dissolution rate would be expected to increase if the pH of dissolution
medium was higher than 3.
• For tablets containing active ingredients, whose solubilities are independent of pH, the
dissolution rate does not vary significantly with changes in pH of the dissolution medium
unless they contain certain excipients that are influenced by pH
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16. Effect of viscosity of the dissolution medium:
• dissolution rate is inversely proportional to the viscosity
• If the rate of contact at the interface is significantly quicker than the rate of transport, as it is
in diffusion controlled dissolution processes, it would be expected that the dissolution rate
decreases with an increase in viscosity.
• For instance, the rate of dissolution of zinc in HCl solution containing sucrose was inversely
proportional to the viscosity of the solution.
Effect of dissolution fluid:
• Selection of proper medium for dissolution testing depends largely on the physicochemical
properties of the drug.
• The nature of dissolution medium influences the solubility.
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17. Volume of dissolution medium and sink conditions:
• The proper volume of dissolution medium depends on the solubility of drug selected fluid.
• If the drug poorly soluble in water a relatively large amount of fluid should be used if
complete dissolution is to be expected.
Effect of temperature of the dissolution medium:
• Drug solubility is temperature dependent, as the temperature increase the solubility of a drug
enhances therefore careful temperature control during the dissolution process is extremely
important.
• Generally, a temperature of 37˚C±0.5 is maintained during dissolution determination of oral
dosage forms and suppositories. For topical preparations, as low as 30˚C and 25 ˚C have
been used.
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18. Effect of surface tension of the dissolution medium:
• If the drug is hydrophobic the dissolution rate is influenced primarily by the release processes,
whereas, for hydrophilic drugs the transfer process is more likely to be the rate limiting step.
• Incorporation of surface active agents in the dissolution medium, is expected to enhance the
dissolution rate of a poorly soluble drug in solid dosage forms by lowering the interfacial
tension between medium and solid surface and micelle formation.
• Addition of surfactant below the CMC (Critical Micelle Concentration) can increase
significantly the dissolution rate
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19. Pharmacokinetic :
Pharmacokinetics is defined as the kinetics of drug absorption, distribution, metabolism and
excretion (KADME) and their relationship with the pharmacologic, therapeutic or
toxicologic response in man and animals.
Pharmacokinetic parameters are:
• Peak plasma concentration (Cmax)
• Time of peak concentration (tmax)
• Area under curve (AUC)
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20. 20
Plasma drug concentration time profile

21. 1. Peak plasma concentration (Cmax)
• The point of maximum concentration of drug in plasma is called as the peak and the
concentration of drug at peak is known as peak plasma concentration. (peak height
concentration and maximum drug concentration.) Cmax is expressed in mg/mL(mcg)
• The peak plasma level depends upon;
 Dose administered
 Rate of absorption
 Rate of elimination
• The peak represents point of time when absorption equals elimination rate drug
• Peak concentration is often related intensity pharmacologic response and should ideally be
above maximum effective concentration (MSC)but less than the maximum safe
concentration(MSC). 21

22. 2. Time of Peak Concentration (tmax)
• The time for drug to reach peak concentration in plasma called time of peak
concentration.
• It is expressed hours and useful in estimating the rate of absorption.
• Onset time and onset action are dependent upon tmax.
• Important in assessing the efficacy of drugs
3. Area Under Curve (AUC)
• It represents the total integrated area under the plasma level-time profile
• expresses total amount of drug comes into the systemic circulation after its administration.
• AUC is expressed mcg/mL*hours.
• It the most important parameter in evaluating bioavailability of drug from its dosage form
Represent extent of absorption 22

23. CONCLUSION :
 The diffusion drug into tissues and their excretion through kidneys can be anticipated
through diffusion studies.
 It has found its applications in determining the molecular weight of polymers, release of
drug from sustained/controlled release dosage forms.
 Dissolution is very important step in the design of dosage form.
 Various parameters such as thickness of membrane, volume of GI fluid, diffusion coefficient
(diffusivity) of the drug etc determines the rate of diffusion and dissolution rate.
 Pharmacokinetic study is also important to identify variables that are important in
determining the potential of success of drug delivery system.
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24. 1. Subrahmanyam C V S. Textbook of physical pharmaceutics. 3rd Ed.
Delhi. Vallabh Prakashan; 2015:96-112,133-148
2. Brahmankar D M , Sunil J B . Biopharmaceutics and
Pharmacokinetics. 3rd Ed. New Delhi. Vallabh Prakashan;2015:28-
31,237-240
3. Venkateswarlu V. Biopharmaceutics and Pharmacokinetics. 2nd Ed.
PharmaMed press;2012;45-69
REFERENCES :
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