This document discusses diffusion principles in biological systems as they relate to drug absorption and delivery. It begins by defining diffusion and outlining Fick's laws of diffusion. It then discusses several examples of diffusion processes: 1) Gastrointestinal drug absorption, where drugs must dissolve and diffuse through the GI membrane layers to enter blood circulation. Absorption depends on factors like surface area, partition coefficient, and ionization state. 2) Percutaneous absorption, with skin as the barrier. Drugs diffuse through stratum corneum, dermis, and subcutaneous layers. 3) Buccal absorption, where drugs diffuse through the lipoidal buccal membrane, following principles like pH-partition hypothesis.

1. Solubility of Drugs:
Diffusion principles in Biological Systems
PRESENTED BY- MR SHUBHRAT MAHESHWARI
ASSISTANT PROFESSOR
FACULTY OF PHARMACEUTICAL SCIENCES
RAMA UNIVERISTY KANPUR
Subject: Physical Pharmaceutics-I
Subject Code: BP302T

2. Diffusion
• Diffusion is defined as a process of mass transfer of
individual molecules of a substance brought about by
random molecular motion and associated with a driving
force such as a concentration gradient.
• The mass transfer of a solvent (e.g., water) or a solute
(e.g., a drug) forms the basis for many important
phenomena in the pharmaceutical sciences.
• For example, diffusion of a drug across a biologic
membrane is required for a drug to be absorbed into and
eliminated from the body, and even for it to get to the site
of action within a particular cell.

3. Diffusion
• In other words movement of substance from a region
of higher concentration to the region of a lower
concentration.

4. Diffusion
Diffusion phenomena applied in pharmaceutical
sciences include:
• Release of drug from dosage form.
• Ultrafiltration, microfiltration, dialysis,
hemodialysis.
• Permeation & distribution of drug in living
tissues.
• Estimation of molecular weight of polymers.
• Prediction of absorption & elimination of drug.

5. General path of drug (Oral administration)

6. • The diffusion principle is described by the
different methods,
A. Passive diffusion
B. Pore transport
C. Ion Pair transport
D. Carrier mediated method
E. Active transport

7. Law of Diffusion
• It is Given by Adolf Fick in 1856.
• The simplest description of diffusion is given by
Fick's laws, which were developed by Adolf Fick in
the 19th century:
• The molar flux due to diffusion is proportional to the
concentration gradient.
1. FICK'S FIRST LAW OF DIFFUSION
2. FICK'S SECOND LAW OF DIFFUSION

8. Fick’s First Law of Diffusion
• According to Fick's law of diffusion,
• "The molar flux due to diffusion is proportional to the
concentration gradient".
• Fick's first law of diffusion is:
J = -D dc/dx
• where D is the diffusion coefficient of a penetrant (also called
the diffusant), C is its concentration in g/cm³, and x is the
distance in centimeters of movement perpendicular to the
surface of the barrier.

9. Fick’s First Law of Diffusion
• It is important to note that:
1. the flux is proportional to the concentration gradient,
dc/dx.
2. the negative sign of equation signifies that diffusion
occurs in a direction (the positive x direction) opposite
to that of increasing concentration. That is, diffusion
occurs in the direction of decreasing concentration of
diffusant; thus, the flux is always a positive quantity.
3. diffusion will stop when the concentration gradient
no longer exists (i.e., when dc/dx = 0).

10. Fick’s Second Law of Diffusion
• Prediction of change in concentration along with time due to diffusion.
• "Change in concentration with time in a particular region is proportional to
the change in concentration gradient at that point in the system.”

11. Diffusion principles in Biological Systems
I. GASTROINTESTINAL DRUG ABSORPTION
II. PERCUTANEOUS DRUG ABSORPTION
III. BUCCAL ABSORPTION
IV. UTERINE DIFFUSION

12. Diffusion principles in Biological Systems
I. GASTROINTESTINAL DRUG ABSORPTION
• A drug taken orally must dissolve first in the GI fluid followed
by its absorption into the blood stream.
• For drug absorption, it needs to pass through the GI membrane
at various locations.
• The GI membrane acts as a barrier and it is composed of
double layer of phospholipids surrounded by protein
molecules. Drug absorption through this membrane occurs by
passive diffusion, pore transport, facilitated diffusion, active
transport, etc.
• Passive diffusion: It is a process in which molecules
spontaneously diffuse from a region of higher concentration to
a region of lower concentration.

13. GASTROINTESTINAL DRUG ABSORPTION (Contd.)
• Drug moves down the concentration gradient.
• The transport process depends on the surface area of
the GI membrane. Thus more drug is absorbed from
the intestine than the stomach.
• It depends on partition coefficient of the drug. Thus
drugs that have high value of K are lipophilic and
diffuse easily across the lipoidal GI membrane.
• Unionised forms, being lipoidal, diffuse easily as
compared to the ionic form.

14. Diffusion principles in Biological Systems
II. PERCUTANEOUS DRUG ABSORPTION
• Percutaneous penetration, or absorption through skin, involves:
(i)Drug dissolution in its vehicle. (ii) Drug diffusion from vehicle to
skin surface. (iii)Drug penetration through skin layers.
• The skin consists of three layers: the epidermis, dermis and
subcutaneous fat layers.
• The epidermis consists of outermost layer of stratum corneum which
is composed of dead, keratinized cells. The stratum corneum is the
main barrier to drug diffusion and once it is overcome, it can easily
enter the dermis and the systemic circulation.
• The process of drug penetration in the stratum corneum is passive
diffusion, which depends on different factors such as hydration of
the stratum corneum, drug properties such as its partition coefficient,
pH, etc.

15. Fig. Skin structures involved in percutaneous absorption. Thickness of layers is not drawn
to scale. Key to sites of percutaneous penetration: A, transcellular; B, diffusion through
channels between cells; C, through sebaceous ducts; D, trans follicular; E, through sweat
ducts.

16. Diffusion principles in Biological Systems
III. BUCCALABSORPTION
• Beckett and Moffat studied the penetration of drugs into the
lipid membrane of the mouths of humans
• In harmony with the pH-partition hypothesis, absorption was
related to the pKa of the compound and its lipid–water
partition coefficient.
• Ho and Higuchi expression applied aqueous lipid phase model
in which the weak acid species are transported across the
aqueous diffusion layer and only the non-ionized species
passed across the lipid membrane.

17. • Unlike the intestinal membrane. the buccal
membrane does not have significant aqueous
pore pathway.
• And the surface pH is essentially the same as
the buffered drug solution pH.
• It follows first order process owing to the non-
accumulation of drug on the blood side.

18. Diffusion principles in Biological Systems
IV. UTERINE DIFFUSION
• Drugs such as progesterone and other therapeutic and
contraceptive compounds may be delivered in microgram
amounts into the uterus by means of diffusion-controlled
forms (intrauterine device).
• In this way the patient is automatically and continuously
provided medication or protected from pregnancy for
days, weeks, or months.
• Yotsuyanagi et al. performed in situ vaginal drug
absorption studies using the rabbit doe as an animal
model to develop more effective uterine drug delivery
systems.

19. • A solution of a model drug was perfused through a specially
constructed cell and implanted in the vagina of the doe (Fig.),
and the drug disappearance was monitored.
• The drug release followed first-order kinetics, and the results
permitted the calculation of apparent permeability coefficient
and diffusion layer thickness.
Fig. Implanted rib-cage cell in the vaginal tract of a rabbit.

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