1. COMPACTION PROFILES,SOLUBILITY ENHANCEMENT
TECHNIQUES,STUDY OF CONSOLIDATION PARAMETERS
(DIFFUSION PARAMETERS,DISSOLUTION PARAMETERS
AND PHARMACOKINETICS PARAMETERS)
PRESENTED BY
NIVEDITHA G
1st sem Mpharm
(Department Of Pharmaceutics)
NARGUND COLLEGE OF PHARMACY
2. COMPACTION PROFILES
• Many attempts have been made to minimize the amount of applied force
transmitted radially to the die walls. All such investigations lead to characteristic
hysteresis curves called as compaction profiles.
Radial pressure is developed due to the attempt of material to expand
horizontally. The plot of radial pressure against axial pressure leads to hysteresis
curve called as compaction profile.
• When the elastic limit of the material is high, elastic deformation may make the
major contribution, and on removal of the applied load, the extent of the elastic
relaxation depends on the value of the material’s modules of elasticity (young’s
modulus).
3. • Lower the modulus higher will be the elastic relaxation. Then there will be the
danger of structural failure.
• Higher the modulus value results in low decompression hence lesser risk of
structural failure
4. •Examples of compaction profiles.
•Dotted line O to A represents a highly variable response due to
repacking.
• At A elastic deformation becomes dominant and continues
until the elastic limit B is reached.
• From B to the point of maximum compression C, deformation
is predominantly plastic, or brittle fracture is taking place.
• The decompression process C to D is accompanied by elastic
recovery, and if a second yield point D is reached.
• Plastic deformation or brittle fracture takes place from D to E.
• And the decompression line B to C represents the behaviour
of a largely elastic material
5. SOLUBILITY ENHANCEMENT TECHNIQUES
• The term ‘solubility’ is defined as maximum amount of solute that can be
dissolved in a given amount of solvent. It can also be defined quantitatively as well
as qualitatively.
• Quantitatively it is defined as the concentration of the solute in a saturated
solution at a certain temperature.
• In qualitative terms, solubility may be defined as the spontaneous interaction of
two or more substances to form a homogenous molecular dispersion.
• The solubility of a drug is represented through various concentration expression
such as parts, percentage, molarity, molality, volume fraction, mole fraction.
6. Need for solubility enhancement
• There are variety of new drugs & their derivatives are
available. But less than 40% of lipophilic drugs candidates fail to
reach market due to poor bioavailability, even though these
drugs might exhibit potential pharmaco-dynamic activities.
• The lipophilic drug that reaches market requires a high dose to
attain proper pharmacological action.
• The basic aim of the further formulation & development is to
make that drug available at proper site of action within optimum
dose.
7. Importance of enhancement
• Solubility is one of the important parameters to achieve desired concentration
of drug in systemic circulation for achieving required pharmacological response.
• Low aqueous solubility is the major problem encountered with formulation
development of new chemical entities as well as generic development. Any drug
to be absorbed must be present in the form of an aqueous solution at the site of
absorption.
The techniques are chosen on the basis of certain aspects such as properties of
drug under consideration, nature of excipients to be selected, and nature of
intended dosage form.
• These poorly water-soluble drugs having slow drug absorption leads to
inadequate and variable bioavailability and gastrointestinal mucosal toxicity.
10. Particle Size Reduction
• The bioavailability intrinsically related to drug particle size. By reducing particle
size, increased surface area improves the dissolution properties.
• Nowadays Particle size reduction can be achieved by micronization and
nanosuspension. The techniques involved in particle size reduction are:
1. Micronization
2. Nanosuspension
11. Micronization
• In micronization the solubility of drug is often intrinsically
related to drug particle size. By reducing the particle size, the
increased surface area improves the dissolution properties of
the drug.
• Micronization increases the dissolution rate of drugs through
increased surface area, it does not increase equilibrium
solubility.
• Micronization of drugs is done by milling techniques using jet
mill, rotor stator colloid mills etc.
12. Micronization is not suitable for drugs having a high dose
number because it does not change the saturation solubility of
the drug.
• These processes were applied to griseofulvin, progesterone,
spironolactone and fenofibrate. For each drug, micronization
improved their digestive absorption, and consequently their
bioavailability and clinical efficacy.
2. Nanosuspension
• Nanosuspension is another technique which is sub-micron
colloidal dispersion of pure particles of drug, which are
stabilized by surfactants.
13. • The advantages offered by nanosuspension is increased dissolution rate is due to
larger surface area exposed, while absence of Ostwald ripening is due to the
uniform and narrow particle size range obtained, which eliminates the
concentration gradient factor.
• Nanosuspensions are produced by homogenization and wet milling process.
• The nanosuspension approach has been employed for drugs including Tarazepide,
Atovaquone, Amphotericin B, Paclitaxel and Bupravaquon.
Modification Of Crystal Habit (or)Crystal Engineering
• The controlled crystallization of drugs to produce high purity powders with well-
defined particle size distribution, crystal habit, crystal form (crystalline or
amorphous), surface nature, and surface energy.
14. • By manipulating the crystallization conditions (use of different solvents or
change in the stirring or adding other components to crystallizing drug
solution) a variety of crystal habit is generated.
• Polymorphs
• Amorphous
• Co crystallization
15. Polymorphs
• It is possible to prepare crystals with different packing arrangement;
such crystals are called polymorphs. As a result, polymorphs for the same
drug may differ in their physicochemical properties such as solubility,
dissolution rate, melting point, and stability.
• Most drugs exhibit structural polymorphism and it is preferable to
develop the most thermodynamically stable polymorph of the drug to
assure reproducible bioavailability of the product over its shelf-life under a
variety of real-world storage conditions.
16. Amorphous
• Amorphous materials exhibit distinct physicochemical properties compared to
their respective crystalline counterparts.
• One of these properties, the increased solubility of amorphous materials, is
exploited in the pharmaceutical industry as a way of increasing bioavailability of
poorly water-soluble drugs.
Co crystallization
• Pharmaceutical cocrystals open a new avenue to address the problems of poorly
soluble drugs. They contain two or more distinct molecules arranged to create a
new crystal form whose properties are often superior to those of each of the
separate entities.
• The pharmaceutical cocrystals are formed between a molecular or ionic drug and
a cocrystal former that is a solid under ambient conditions.
17. • These are prepared by slow evaporation from a drug solution containing
stoichiometric amounts of the components (cocrystal formers); however,
sublimation, growth from the melt, or grinding of two or more solid
cocrystal formers in a ball mill are also suitable methodologies
SUPERCRITICAL FLUID RECRYSTALLIZATION(SCF)
• Those fluids are referred to as supercritical fluids which are having
temperature and pressure greater than its critical temperature and critical
pressure so as they are acquire properties of both gas and liquid e.g.:-carbon
dioxide.
• As the drug gets solubilized within SCF they can be recrystallized with
reduced particle size of drug
18. SONOCRYSTALLISATION
• The novel approach for particle size reduction on the basis of crystallization
by using ultrasound is Sonocrystallisation.
• Sonocrystallisation utilizes ultrasound power characterized by a frequency
range of 20–100 kHz for inducing crystallization.
• It’s not only enhances the nucleation rate but also an effective means of size
reduction and controlling size distribution of the active pharmaceutical
ingredients.
• Most applications use ultrasound in the range 20 kHz-5 MHz.
19. Drug Dispersion Carriers Eutectic mixtures
• Its potential as a system to improve the solubility and dissolution of
poorly water-soluble drugs.
• When the eutectic mixture is exposed to water the soluble carrier
dissolves leaving the drug in a microcrystalline state which solubilize
rapidly. Solid dispersions
• The term solid dispersion refers to a group of solid products consisting
of at least two different components, generally a hydrophilic matrix and a
hydrophobic drug.
• In this technique, a poorly soluble drug is dispersed in a highly soluble
solid hydrophilic matrix, which enhances the dissolution of the drug
20. Solid dispersions
These are prepared by using several methods, such as the fusion
(melt) method and the solvent method
• The most commonly used hydrophilic carriers for solid dispersions
include polyvinylpyrrolidone (Povidone, PVP), polyethylene glycols
(PEGs), PlasdoneS630.
• Surfactants like Tween-80, docusate sodium, and sodium lauryl
sulphate (SLS) also find a place in the formulation of solid dispersion.
• A solid dispersion of griseofulvin and polyethylene glycol 8000 (Gris-
PEG®) is commercially available
21. 1. Solid solutions
• Solid solutions are generally made by the “melt method” or the “solution
method”
• In the solution method, API and excipients are co-dissolved in a solvent,
which is then removed to form the dosage form.
• Two components crystallize together in a homogeneous one phase system,
because of reduction in particle size to the molecular level solid solution
shows greater aqueous solubility.
• E.g., Griseofulvin from such solid solution dissolves 6-7 times faster than
pure form.
22. 2. Cryogenic techniques
• It is developed to enhance the dissolution rate of drugs by creating
nanostructured amorphous drug particles with high degree of porosity at
very low-temperature conditions.
• Cryogenic inventions can be defined by the type of injection device
(capillary, rotary, pneumatic, and ultrasonic nozzle), location of nozzle
(above or under the liquid level), and the composition of cryogenic liquid
(hydrofluoroalkanes, N2, Ar, O2, and organic solvents).
24. pH Adjustment
• Poorly water-soluble drugs with parts of the molecule that can be protonated
(base) or deprotonated (acid) may potentially be dissolved in water by applying
a pH change. pH adjustment can in principle be used for both oral and
parenteral administration.
• In the stomach the pH is around 1 to 2 and in the duodenum the pH is
between 5-7.5, so upon oral administration the degree of solubility is also likely
be influenced as the drug passes through the intestines. Ionizable compounds
that are stable and soluble after pH adjustment are best suited.
• pH adjustment is also frequently combined with co-solvents to further
increase the solubility of the poorly soluble drug.
25. Use of buffer
Buffer maintains the pH of the solution overtime and it reduces or eliminate
the potential for precipitation upon dilution. On dilution pH alteration occurs
that decrease solubility.
• Change of pH by 1 fold increase solubility by 10fold if it changes by one pH
unit, that decrease ionisation of the drug and solubility decreases by 10 fold
Derivatization
• It is a technique used in chemistry which transforms a chemical compound
into a product of similar chemical structure, called derivative.
• Derivatives have different solubility as that of adduct. It is used for
qualification of adduct formation of esters and amides via acyl chlorides.
26. Complexation
• Complexation of drugs with cyclodextrins has been used to enhance
aqueous solubility and drug stability.
• Cyclodextrins of pharmaceutical relevance contain 6, 7 or 8 dextrose
molecules (α, β, γcyclodextrin) bound in a 1,4-configuration to form rings of
various diameters.
• The ring has a hydrophilic exterior and lipophilic core in which
appropriately sized organic molecules can form noncovalent inclusion
complexes resulting in increased aqueous solubility and chemical stability.
• Complexation relies on relatively weak forces such as London forces,
hydrogen bonding and hydrophobic interactions
27. Technique Of Complexation
Physical Mixture.
1. Kneading Method
• Active drug with suitable polymer in different ratios is added to the
mortar and triturated with small quantity of ethanol to prepare a
slurry
• Slowly the drug is incorporated into the slurry with constant
trituration. The prepared slurry is then air dried at 250 for 24hrs.
• The resultant product is pulverized and passed through sieve no. 80
and stored in desiccator over fused calcium chloride
28. 2.Co-precipitate Method
• Active drug is dissolved in ethanol at room temperature and
suitable polymer is dissolved in distilled water.
• Different molar ratios of active drug and suitable polymers are
mixed respectively
• The mixture is stirred at room temperature for one hour and the
solvent is evaporated. The resultant mass is pulverized and
passed through sieve no. 80 and stored in a desiccator
29. 3.SPRAY DRYING
• The solvent evaporation of drug and polymer solution in different ratio is
carried out by using spray dryer.
• The solutions are prepared by dissolving drug in methanol and polymer in
distilled water and mix both solutions, which produces a clear solution.
• The solvent evaporated by using evaporator.
• The spray dried mixture of drug with polymer is obtained in 20–30 min.
4. INCLUSION COMPLEX FORMATION
• Inclusion complexes are formed by the insertion of the nonpolar molecule or
the nonpolar region of one molecule (known as guest) into the cavity of another
molecule or group of molecules (known as host). EX b- cyclodextrin
30. • The cavity of host must be large enough to accommodate the guest and small
enough to eliminate water, so that the total contact between the water and the
nonpolar regions of the host and the guest is reduced
TECHNIQUES OF INCLUSION COMPLEX METHOD
1.Lyophilization/Freeze-Drying Technique:
➢ In order to get a porous, amorphous powder with high degree of interaction
between drug and CD.
➢ In this technique, the solvent system from the solution is eliminated
➢ through a primary freezing and subsequent drying of the solution containing
both drug and CD at reduced pressure.
➢ Thermolabile substances can be successfully made into complex form by this
method
31. 2.Microwave Irradiation Method:
➢ This technique involves the microwave irradiation reaction between drug and
complexing agent using a microwave oven.
SALT FORMATION
• Dissolution rate of particular salt is usually different from that of parent
compound.
• Sodium and potassium salt of week acid dissolve more rapidly than that of pure
salt.
❑ Limitation of salt formation-
➢ Epigastric distress due to high alkalinity,
➢ Reactivity with atmospheric water and carbon dioxide leads to precipitation,
➢ Patient compliance and commercialization.
32. Miscellaneous Surfactant
• Surfactants are the agents which reduces surface tension and enhance the
dissolution of lipophilic drugs in aqueous medium.
• The surfactants are also used to stabilize drug suspensions.
• When the concentration of surfactants more than their critical micelle
concentration (CMC, which is in the range of 0.05–0.10% for most surfactants),
micelle formation occurs which entrap the drugs within the micelles. This is
known as micellization and generally results in enhanced solubility of poorly
soluble drugs.
Microemulsions
• A microemulsion is an optically clear pre-concentrate containing a mixture of
oil, hydrophilic surfactant and hydrophilic solvent which dissolves a poorly water-
soluble drug.
33. • Microemulsions have been employed to increase the solubility of many drugs
that are practically insoluble in water, along with incorporation of proteins for
oral, parenteral, as well as percutaneous / transdermal use
SOLUBILIZERS
• The solubility of poorly soluble drug can also be improved by various
solubilizing materials.
• PEG 400 is improving the solubility of hydrochlorthiazide 85.
• Modified gum karaya a recently developed excipient was evaluated as carrier
for dissolution enhancement of poorly soluble drug nimodipine.
34. COSOLVENCY
• The solubility of poorly soluble drugs in water can be increased by mixing it
with some water miscible solvent in which the drug is readily soluble. This
process is known as co solvency and the solvent used in combination are known
as cosolvent.
• The cosolvents are having hydrogen acceptor or donor groups with a small
hydrocarbon region.
• The hydrophobic hydrocarbon region usually interferes with the hydrogen
bonding network of water which consequently reduces the intermolecular
attraction of water while the hydrophilic hydrogen bonds ensures water
solubility.
35. HYDROTROPY
➢ Hydrotropy is a solubilization phenomenon whereby addition of
large amount of a second solute results in an increase in the aqueous
solubility of existing solute.
➢ Concentrated aqueous hydrotropic solutions of sodium benzoate,
sodium salicylate, urea, nicotinamide, sodium citrate, and sodium
acetate have been observed to enhance the aqueous solubilities of
many poorly water-soluble drug.
36. Applications of solubility
• Solubility is representing a fundamental concept in fields of research such as
chemistry, physics, food science, pharmaceutical, and biological sciences.
• The solubility of a substance becomes especially important in the
pharmaceutical field because it often represents a major factor that controls the
bioavailability of a drug substance.
• Solubility is commonly used to describe the substance, to indicate a
substance's polarity, to help to distinguish it from other substances, and as a
guide to applications of the substance.
• Solubility of a substance is useful when separating mixtures.
• Moreover, solubility and solubility-related properties can also provide
important information regarding the structure of drug substances, and in their
range of possible intermolecular interactions.
• It is used for enhancing solubility of class 2 drugs of BCS
37. Diffusion, Dissolution and Pharmacokinetic parameters
Diffusion: Diffusion is the movement of a substance from an area of high
concentration to an area of low concentration.
• Diffusion happens in liquids and gases because their particles move
randomly from place to place.
• The material that undergoes diffusion is known as diffusant or permeant
or penetrant.
38. Example: 1. When shaking salt into water, the salt dissolves and the ions move
until they are evenly distributed.
2. After placing a drop of food coloring onto a square of gelatin, the color will
spread to a lighter color throughout the block.
Factors affecting diffusion.
1. Temperature : Higher temperature diffuse faster
2. Surface area : Larger surface area greater in diffusion
3. Concentration : Higher the concentration gradient greater the diffusion
4. Particle size: Smaller the particles greater the diffusion.
Diffusion parameters
This is given by Higuchi. 𝑄 = 𝐾 𝑻 Where, Q is the amount of drug released in
time‘t’ per unit area
39. • K is higuchi constant, T is time in hr.
• Plot: The data obtained is to be plotted as cumulative percentage
drug release versus Square root of time.
• Application: modified release pharmaceutical dosage forms,
transdermal systems and matrix tablets with water soluble drugs.
Dissolution : Dissolution is a process in which a solid substance
solubilizes in a given solvent i.e. mass transfer from the solid surface to
the liquid phase. Example; Tablet when comes in contact with
surrounding liquid tablet gets converted in liquid phase
40. Dissolution parameters:
1. Effect of agitation.
2. Influence of pH of dissolution fluid.
3. Effect of surface tension of the dissolution medium.
4. Effect of viscosity of the dissolution medium
5. Effect of the presence of unreactive and reactive additives in the dissolution
medium.
6. Volume of dissolution medium and sink conditions.
7. Deaeration of the dissolution medium.
8. Effect of temperature of the dissolution medium.
9. Volume of dissolution medium and sink conditions.
10. Deaeration of the dissolution medium.
11. Effect of temperature of the dissolution medium
41. 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.
❑ Accordingly, the compendial methods in general, are conducted under
relatively low agitation.
❑ For the basket method, 50 or 100 rpm usually is utilized, while for the
paddle procedure, a 50 rpm is recommended.
❑ In case of the non official continuous flow, column type methods, a flow
rate of 10 – 100 ml/min commonly is employed
42. Influence of pH of dissolution fluid
• it was observed that USP XV included simulated gastric fluid as the
test medium for tablets containing ingredients which reacted more
readily in acid solution than in water (e.g., calcium carbonate).
❑ The medium again was changed to water in the USP XVIII.
❑ Changes in pH exert the greatest effect in terms of drug solubility.
❑ For weak acids, the dissolution rate increases with increasing pH,
whereas, for weak bases, the dissolution rate increases with decreasing
pH.
❑ Therefore for acetylsalicylic acid (pKa=3.5) tablets and capsules, the
dissolution rate would be expected to increase if the pH of the
dissolution medium was higher than 3.
43. • ❑ 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.
• ❑ For example, Tablets that are formulated with carbon dioxide
producing compounds, such as sodium bicarbonate, magnesium
carbonate or calcium carbonate, tend to have slightly faster dissolution
rate in acid medium than in water because rapid disintegration
increases the effective surface area.
44. Effect of surface tension of the dissolution medium
• According to the diffusion film theory, dissolution of the drug is governed
by the interplay between two processes, the release of the drug from the
solid surface and its transfer throughout the bulk 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 reducing the interfacial tension and micelle formation.
• Addition of surfactant below the Critical micelle concentration (CMC) can
increase significantly the dissolution rate because of better penetration of
the solvent into the tablet resulting in greater availability if drug surface.
45. Effect of viscosity of the dissolution medium
• If the interaction at the interfaces, occurs much faster than the rate of transport,
such as in the case of diffusion controlled dissolution processes, it would be
expected that the dissolution rate decreases with an increase in viscosity.
▪ The rate of dissolution of zinc in HCl solution containing sucrose was inversely
proportional to the viscosity of solution.
▪ The stokes- Einstein equation expresses the diffusion
▪ coefficient as a function of viscosity, as can be seen from the following treatment
𝐷 = μ𝑘𝑇
▪ D= diffusion coefficient
▪ μ = mobility (velocity at a force of one dyne)
▪ k = Boltzmann constant (1.38 × 10− 16 )
▪ T=temperature
46. Effect of the presence of unreactive and reactive additives in the
dissolution medium
• When neutral ionic compounds, such as sodium chloride and sodium
sulfate, or non ionic organic compounds, such as dextrose, were added
to the dissolution medium the dissolution of benzoic acid was dependent
linearly upon its solubility in the particular solvent.
• • When certain buffers or bases were added to the aqueous solvent , an
increase in the dissolution rate was observed
47. Volume of dissolution medium and sink conditions
The proper volume of the dissolution medium depends mainly on the
solubility of the drug in the selected fluid.
• If the drug is poorly soluble in water, a relatively large amount of
fluid should be used if complete dissolution is to be expected.
• In order to maintain the effect of the concentration gradient and
maintain sink conditions, the concentration of the drug should not
exceed 10 – 15% of its maximum solubility in the dissolution medium
selected
48. Deaeration of the dissolution medium
Presence of dissolved air or other gases in the dissolution medium may
influence the dissolution rate of certain formulations and lead to
variable and unreliable results.
• Example, the dissolved air in distilled water could significantly lower
its pH and consequently affect the dissolution rate of drugs that are
sensitive to pH changes, e.g., weak acids.
• Another serious effect is the tendency of the dissolved air to be
released from the medium in the form of tiny air bubbles that circulate
at random and invariably affect the of the hydrodynamic flow pattern
generated by the stirring mechanism.
• The gathering of air bubbles on the solid surface could also lead to a
reduction in the specific gravity to the point where the tablet, or its
disintegrating powder bed, float to the top of the basket in the liquid
medium with a minimum chance of being wetted efficiently
49. Effect of temperature of the dissolution medium:
Drug solubility is dependent on temperature, therefore careful
temperature control during the dissolution process is extremely
important.
➢ Generally a temperature of 37°±0.5 is maintained during dissolution
determination of oral dosage forms and suppositories.
➢ For topical preparations as low as 30° and 25°have been used.
➢ The effect of temperature variations of the dissolution medium
depends on the temperature/ solubility curves of the drug and the
excipients in the formulation.
➢ Carstetensen pointed out that for a diffusion coefficient D is
dependent upon the temperature.
50. • Carstensen gave an equation
𝑈𝑘𝑇 Where,
U = mobility ( defined as the velocity when exposed to a force of one dyne)
k = Boltzmann constant
T = absolute temperature
Hixson-Crowells cube root law:
Hixson and Crowell described this
➢ W0 1/3 − Wt 1 /3 = Kt Where,
W0 is the initial amount of drug
Wt is the remaining amount of drug at time t .
51. Plot:
Data is to be plotted as cube root of drug percentage remaining in matrix versus
time.
➢ Application:
• This expression applies to pharmaceutical dosage form such as tablets, where
the dissolution occurs in planes that are parallel to the drug surface if the tablet
dimensions diminish proportionally in such a manner that the initial geometrical
form keeps constant all the time.
52. Pharmacokinetic parameters
• Pharmacokinetics is defined as the kinetics of drug absorption,
distribution, metabolism, and excretion and their relationship with
pharmacologic, therapeutic or toxicologic response in humans and
animals.
53. • Three important pharmacokinetic parameters
1.Peak plasma concentration (Cmax)
2. Time of peak concentration (tmax)
3. Area under the curve (AUC)
Peak plasma concentration (Cmax)
The point of maximum concentration of a drug in plasma is called as
peak and the concentration of drug at peak is known as peak plasma
concentration.
❖ It is also called as peak height concentration and maximum drug
concentration.
❖ Cmax is expressed in µg/ml
54. Time of peak concentration (tmax)
• The time for drug to reach peak concentration in plasma ( after
extravascular administration) is called the time of peak concentration.
• ✓ It is expressed in hours. Onset time and onset of action is
dependent upon tmax.
• ✓ The parameter is of particular importance in assessing the efficacy
of drugs used to treat acute conditions like pain and insomnia.
55. Area under the curve (AUC)
• It represents the total integrated area under the plasma level-time
profile and expresses the total amount of drug that comes into the
systemic circulation after its administration.
❖ AUC is expressed in µg/ml x Hours.
❖ It is important for the dugs that are administered repetitively for the
treatment of chronic conditions like asthma or epilepsy