Ivivc sahilhusen

1. IN-VIVO AND IN-VITRO
CORRELATION (IVIVC)
1
GUIDED BY:

Dr. M. R. PATEL
Principale & HOD in
pharmaceutics
DEPARTMENT OF PHARMACEUTICS
SHRI B. M. SHAH COLLEGE OF PHARMACEUTICAL EDUCATION AND REASERCH, MODASA-2013
PRESENTEDE BY:
SAHILHUSEN I . JETHARA
M. PHARM – I (2013-14)
ROLL NO. - 02

2. CONTENTS
INTRODUCTION
IVIVC BASIC
CRITERIA FOR IVIVC
OBJECTIVE OF IVIVC
NEED FOR IVIVC
IMPORTANCE OF IVIVC
FACTORS AFFECTING IVIVC
SOME COMMAN TERMS
LEVELS OF CORRELATION
OVERALL APPROACH
CORRELATION METHODS
APPLICATIONS OF IVIVC
STUDY QUESTIONS
REFERENCES
2

3. WHAT IS IVIVC???
•In IVIVC, "C" denotes "Correlation", which means "the degree of
relationship between two variables". This term does not limit a
relationship to only the linear type, but allows for non-linear
relationships as well.
USP definition
•“The establishment of rational relationship b/w a biological
property or a parameter derived from a biological property
produced by a dosage form and physicochemical property of
same dosage form”
•Conceptually, IVIVC describes a relationship between the in vitro
dissolution / release versus the in vivo absorption.
FDA definition
•“A predictive mathematical model describing relationship between
in-vitro property of a dosage form and in-vivo response.”
3

4. IVIVC BASIC
•Simply a mathematical model describing the relationship
b/w in vitro and in vivo properties of drug.
•In vitro –in vivo correlation can be achieved using
Pharmacological correlation
“Based on clinical observations”
Semi quantitative correlation
“Based on the drug blood levels or urinary excretion data”
Quantitative correlation
“Arising from absorption kinetics and calculation of in vivo dissolution
rate and absorption rate constants”
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5. CRITERIA FOR IVIVC
•Successful IVIVC can be developed when in-vitro dissolution is rate
limiting step in absorption and appearance of drug in in- vivo
circulation following oral or other routes of administration.
•These studies are to be conducted during the early stages of drug
product development in order to select the most effective
formulation and to establish appropriate dosage regimen.
•The release- controlling excipients in the formulations should either
be identical or very similar.
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6. OBJECTIVE OF IVIVC
•To reduce the number of human studies during the formulation
development
•To serve as a surrogate for in vivo bioavailability
•To support biowaivers.
•To validates the use of dissolution methods and specification
settings(This is because the IVIVC includes in vivo relevance to in
vitro dissolution specifications).
•To assist quality control for certain scale-up and post-approval
changes (SUPAC).
•Due to all above objective, such IVIVC leads to
1. Shortens the drug development period,
2. Economizes the resources and
3. Leads to improved product quality.
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7. NEED FOR IVIVC
•Theoretically, correlation of in-vivo absorption rate with clinical response will be
the most worthwhile approach. But, clinical approach is a poor tool for accurate
measurement of bioavailability.
•Determination of drug level at the site of administration would be next logical
approach. But again, with some exceptions, it‘s impossible.
•Urinary excretion analysis of drug is meaningful for establishing IVIVC but due to
complicated pharmacokinetic considerations, such as drug metabolism and urine
collection problems.thus it is generally assumed that blood(serum/plasma) level
measurements give a better assessment of bioavailability and bioequivalence.
•This relationship is an important item of research in the development of drug
delivery systems.
•A good IVIVC model can explore the relationship between in vitro dissolution or
release and in vivo absorption profiles.
•The IVIVC model relationship facilities the rational development and evaluation
of immediate or extended release dosage form as a tool for formulation
screening ,in setting dissolution specifications and as a surrogate for
bioequivalence testing.
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8. 8
To explore the
relationship
To assist
quality
control
for certain
SUPAC.
Research tool
for
Formulation
Screening
To support
biowaivers
for
bioequivalence
testing
Development of
drug delivery
systems.
To set the
dissolution
specifications
As a surrogate
of in vivo
bioavailability
To reduce
the number of
human studies
IMPORTANCE
OF
IVIVC

9. FACTORS AFFECTING DEVELOPMENT OF
A PREDICTABLE IVIVC
1.Complexity of the delivery system.
2.Composition of formulation.
3.Method of manufacture.
4.Physicochemical properties.
5.Dissolution method.
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10. 1. Physicochemical properties of drug
A. Factors affecting solubility
a. Polymorphism
b. Amorphous state and solvation
c. Free acid, free base or salt form
d. Complexation, solid solutions and eutectics
e. Particle size
f. Surfactant
B. Factors affecting surface area available for dissolution
a. Particle size
b. Manufacturing variables
•The physicochemical properties of the drug substance can assume a primary role
in controlling its dissolution from the dosage form.
•The aqueous solubility of the drug is one of the major factors that determine its
dissolution rate.
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11. •Some studies concluded that the drug solubility data can be used as rough
predictor of the possibility of any future problems with bioavailability.
•Some of the more prominent physicochemical properties of the drug that
influence the dissolution rate are discussed below.
Polymorphism
•Polymorphic forms of a drug substance are an indicative of different
crystalline forms. With a change in the crystalline form, there is a change in
the lattice energy level associated with each form.
•This energy is responsible for physicochemical properties such as
solubilizing potential and dissolution rate.
•Metastable (high activation energy) polymorphic forms have better
dissolution than stable forms.
•This phenomenon is particularly applicable to steroids.
•As a result, crystallographic modifications can significantly influences
dissolution of drug substance itself as well as the dosage unit it is contained
within.
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12. 2. Factors related to Composition of formulation
•Most solid dosage forms incorporate more than one excipient for various purposes
together with the active ingredient in the formulation. The dissolution rate of a
pure drug can be altered significantly when mixed with various adjuncts.
•These adjuncts include diluents, binders, lubricants, granulating agents,
disintegrants, etc.
a.Excipients and additives
b.Binders and granulating agents
c.Disintegrating agents
d.Lubricants
e.Surfactants
f.Water soluble dyes
g.Coating polymers
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13. Surfactants
•They enhance the dissolution rate of poorly soluble drug. This is due to lowering of
interfacial tension between the drug and dissolution medium, increasing effective
surface area, which in turn results in faster dissolution rate.
•Additionally, the method of incorporation of surfactant in the drug product
formulations can markedly affect the dissolution characteristics of the relatively
hydrophobic drug.
•E.g Non-ionic surfactant Polysorbate 80 increase dissolution rate of phenacetin
granules. The increase was more pronounced when the surfactant was sprayed on
granules than when it was dissolved in gelatin as granulating agent.
Water soluble dyes
•Dissolution rate of single crystal of sulphathiazole was found to decrease
significantly in presence of FD&C Blue No.1. The inhibiting effect was related to
preferential adsorption of dye molecules on primary dissolution sources of crystal
surfaces. They inhibit the micellar solubilization effect of bile salts on drug.
•Cationic dyes are more reactive in lower conc. than are anionic dyes.
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14. Lubricants
•Lubricants that are commonly incorporated in the formulation of solid dosage
forms fall predominantly in the class of hydrophobic compounds.
•The nature, quality, quantity and method of addition of the lubricant can affect
the dissolution rate. It should be added in small amount (1% or less) and should be
tumbled or mixed gently for only very short time. Prolonged mixing increases the
dissolution time.
•Stearates and talc are hydrophobic in nature tend to retard the dissolution rate by
decreasing the effective surface drug solvent interfacial area by changing the
surface characteristics of the tablets, which reduces wettability and prolonging its
disintegration time.
•If an enhancing effect in dissolution of hydrophobic granules is desired, water
soluble lubricant such as SLS or CARBOWAXES may be used.
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15. 3. Method of manufacture
a.Method of granulation
b.Granule size
c.Compression force
d.Drug- excipient interaction
e.Storage of dosage form
Granule size
•The nature of the granule affects the dissolution rate of the dosage form.
The granule size has little effect on the dissolution rate if the granules are
relatively soft and disintegrate easily. However, if they are harder and
disintegrate more slowly, the granule size will be of importance and an
increase in size will cause a decrease in dissolution rate.
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16. Storage of dosage form
•The effect of aging of tablets, capsules and other solid dosage forms should always
result in a decrease in a dissolution rate. However, an increase in dissolution rate
may also be found. In many cases, however, there is no effect at all.
•Dissolution rate of Hydrochlorthiazide tablets granulated with acacia exhibited
decrease in dissolution rate during 1 yr of aging at R.T. A similar decrease was
observed in tablets stored for 14 days at 50-80ºC or for 4 weeks at 37ºC.
•For tablets granulated with PVP there was no change at elevated temperature but
slight decrease at R.T. Tablets with starch gave no change in dissoln rate either at
R.T. or at elevated temperature.
Drug- excipient interaction
•These interactions occur during any unit operation such as mixing, milling,
blending, drying, and/or granulating result change in dissolution.
•The dissolution of prednisolone found to depend on the length of mixing time with
Mgstearate Similar as increase in mixing time of formulation containing 97 to 99%
microcrystalline cellulose or another slightly swelling disintegrant result in enhance
dissolution rate.
•Polysorbate-80 used as excipient in capsules causes formation of formaldehyde by
autoxidation which causes film formation by denaturing the inner surface of
capsule. This causes decrease in dissoln rate of capsules.
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17. Compression force
•The compression process influence density, porosity, hardness, disintegration time
&dissolution of tablet.
•First condition, higher compression force increase the density & hardness of
tablet, decrease porosity & hence penetrability of solvent into the tablet retard
the wettability by forming a firmer & more effective sealing layer by the lubricant
and in many case tighter bonding between the particle so decrease dissolution
rate of tablet.
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18. •Second condition, higher compression force
cause deformation, crushing or fracture of
drug particles into smaller ones or convert
spherical granules into disc shaped particles
with a large increase in the effective surface
area so increase in dissolution rate.
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• Combination of both conditions can occur;
• In short dissolution decrease at lower pressure (better bonding), then increase at
higher pressure (crushing effect) and decrease again with further increase in pressure
bcz of extra rebonding and formation of denser tablets with poorer dissolution
characteristics.

19. 4. Factors related to complexity of delivery system
•Among the most significant factors that control the process of dissolution are the
type and nature of the dosage form within which the active ingredient is
contained.
•The process of dissolution of an active ingredient from solid pharmaceutical
dosage forms involves several intermediate physicochemical steps, such as
wetting, swelling capillarity, solubility and diffusion.
•With the exception of non disintegrating dosage forms, most solid dosage forms
undergo a somewhat common sequence of events during the process of
dissolution in vitro.
•These events can be delineated as three different types of descriptive categories:
A.Process parameters
B.Theoretical parameters
C.Dissolution testing device parameters
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20. A. Process parameters
NO Process
Parameters modelistic
(theoretical)
Dissolution testing
Device
1Introduction of dosage
form
In dissolution medium
Wetting of dosage form Type of device
2 Sampling Penetration of dissolution
medium into the dosage unit
Operating
characteristics
3 Assay De-aggregation and / or
de-agglomeration
Wetting of drug
Solubilization /dissolution of the
drug
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21. B. Theoretical parameters
1.Wetting of dosage unit
2.De-aggregation /De-agglomeration
3.Dissolution of powders
4.Dissolution of capsules
5.Dissolution of tablets
6.Dissolution of suppositories
7.Dissolution of suspensions
8.Dissolution of modified release dosage forms
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Wetting of dosage unit
•The first step in the process of dissolution is the wetting of the external surface of the
dosage form. The degree and extent to which the surface is wetted are a function of the
interfacial tension at the solid liquid interphase. Additionally, the process of wetting is a
function of the contact angle the liquid makes with the solid surface.
•The more hydrophobic the powder is, the slower the wetting and subsequent penetration
of the dissolution medium across the solid surface barrier.
•In the case of the tablets, granules prepared by the wet granulation process can produce
lower contact angle values, a result attributed to the hydrophilization phenomenon
associated with hydrophobic surfaces, thus promoting wetting.

22. 5.Environmental factors during Dissolution
a)Factors related to the dissolution testing apparatus
1.Eccentricity of agitating (stirring) element
2.Vibration
3.Agitation intensity
4.Stirring element alignment
5.Flow pattern disturbances
6.Sampling probes, position and filters
7.Dosage form position
8.Type of device
b) Factors related to dissolution test parameters
1.Dissolution medium
2.Temperature
- Viscosity
- Volume of dissolution medium and sink conditions
- Dissolved gases – air
- Dissolution composition media and pH
22

23. Eccentricity of agitating (stirring) element
•Official compendium specifies that the stirring shaft must rotate without
significant wobble. Eccentricity can induce and propagate changes in
hydrodynamic conditions and flow patterns that can, influence the dissolution
behavior of the product.
Vibration
•It can affect change in the flow patterns of the dissolution medium. Additionally, it
can introduce unwanted energy to the dynamic system. Both effects may result in
significant changes in dissolution rate.
•It must be noted that no device is free of vibration. The objective of conducting
dissolution testing should be to reduce vibration from external sources to a
manageable level that will not introduce significant variation in results from
successive dissolution tests on the same product.
Stirring element alignment
•USP states that the axis of the stirring element must not deviate more than 2 mm
from the axis of the dissolution vessel.
•A series of tests suggest that a tilt in excess of 1.5
0
may increase in dissolution rates
using method 2 from 2 to 25%.
23

24. SOME COMMAN TERMS
A) MEAN ABSORPTION TIME: The mean time required for drug to reach systemic
circulation from the time of drug administration.
MAT = MRToral - MRTi.v.
B) MEAN IN-VIVO DISSOLUTION TIME: It reflects the mean time for drug to
dissolve in-vivo. For solid dosage form:
MDTsolid = MRTsolid - MRTsolution.
C) MEAN RESIDENCE TIME: The mean time that the drug resides in the body.
Also known as mean transit time.
MRT = AUMC / AUC.
Where, AUMC = Area under first moment Curve (Concentration*time Vs time)
AUC = Area under curve (Concentration Vs time)
D) PERCENT PREDICTION ERROR:
% PE = [(observed value - Predicted value) / observed value] x 100
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25. LEVELS OF CORRELATION
•There are five levels of IVIVC, which include levels A, B, C,
multiple C and D.
1.LEVEL A CORRELATION
2.LEVEL B CORRELATION
3.LEVEL C CORRELATION
4.MULTIPLE LEVEL C CORRELATIONS
5.LEVEL D CORRELATION
25

26. 1. LEVEL A CORRELATION
•Point-to-Point relationship
•Usually Correlations are linear, and no
formal guidance on the non-linear IVIVC.
•The data treatment involves a two stage
Deconvolution Method.
1.Estimation of the in vivo absorption profile
using Wagner-Nelson or Loo-Riegelman
method
2.Comparison of fraction of drug absorbed
(Fa) and fraction of drug dissolved (Fd) in-
vitro to obtain a linear correlation.
•Formulations showing Level A correlation
require no additional human studies to
justify change in manufacturing site, raw
material supplier or minor formulation
changes.
•Most informative and very useful from a
regulatory perspective.
•PURPOSE – DEFINE DIRECT RELATIONSHIP
26

27. Importants of level A correlation
•Providing process control and quality assurance
•Determining stable release characteristics of the
product over time.
•facilitating certain regulatory determinations
(e.g.,absence of effect of minor formulation
changes or of change in manufacturing site on
performance).
27

28. 2. LEVEL B CORRELATION
•A predictive model for relationship
between summary parameters that
characterize the in-vitro and in-vivo time
course.
•No point to point correlation
•It compares
1.MDT vitro to MDT vivo,
2.MDT vitro to MRT,
3.In-vitro Dissolution Rate Constant (kd) to
Absorption Rate Constant (ka).
•Comparison using Statistical moment
analytical method.
•This type of correlation uses all of the in
vitro and in vivo data.
•This is of limited interest and least useful
for regulatory purposes because more than
one kind of plasma curve produces similar
MRT.
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29. 3. LEVEL C CORRELATION
•Mathematical model of relationship between
the amount of drug dissolved in-vitro at a
particular time and a summary pharmacokinetic
parameter that characterizes in-vivo time
course. (e.g., Cmax, Tmax, T1/2 or AUC).
•Single point correlation
•Level C correlations can be useful in the early
stages of formulation development when pilot
formulations are being selected.
•Lowest correlation level
•Does not reflect a complete shape of plasma
concentration time curve.
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30. 4. MULTIPLE LEVEL C CORRELATIONS
•It relates one or more pharmacokinetic parameters to the percent drug dissolved at
several time points of dissolution profile and thus may be more useful.
•If a multiple Level C correlation is possible, then a Level A correlation is also likely
and is preferred.
30
Level In vitro In vivo
A Dissolution curve Input (absorption) curves
B Statistical Moment: MDT Statistical Moment: MRT, MAT
C Disintegration time, Time to
have 10, 50, 90% Dissolved,
Dissolution rate, Dissolution
efficiency
C
max
, T
max
, K
a
, Time to have 10, 50,
90% absorbed, AUC

31. 5. LEVEL D CORRELATION
•Level D correlation is a rank order and qualitative analysis and is not
considered useful for regulatory purposes. It is not a formal correlation but
serves as an aid in the development of a formulation or processing
procedure.
NOTE:-
•Level B and C correlations can be useful in early formulation development,
including selecting the appropriate excipients, to optimize manufacturing
processes, for quality control purposes, and to characterize the release patterns
of newly formulated immediate-release and modified-release products relative
to the reference.
31

32. BCS Class PK Data IVIVR
API –
Physicochemi-
cal Properties
Scale factor
Dosage Form
Properties
Biorelevent
Dissolution
Computer Modeling Using Convolution including Transporters, PK Models,
and PK Parameters, API properties or Drug Release Data
IVIVC
1
2
3
Overall Approach
Wang et al (2009) Diss Tech, 8, 6-12

33. CORRELATION METHODS
33

34. 1.SIMPLE POINT TYPE
•The percentage of drug dissolved in a given time or the time
taken for a certain percentage of drug to be dissolved, is
correlated with certain parameter of the bioavailability.
1.COMPARISON OF PROFILES
•The entire in vivo response time profile can be correlated to the
entire dissolution rate time curve.
•Some of the in vivo and in vitro parameters employed for
correlation are as follows.
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35. 35
In vitro data In vivo data
1.Percent drug dissolution profile
oPercent drug dissolved at time t,
oTime taken for maximum amount of drug to
dissolve.
oTotal amt. of drug dissolved.
oTime for a certain percentage of drug to dissolve
such as t30% t50% t90%
1.Plasma conc. time profile

oPlasma concentration at time t,
oCmax,
otmax,
oAUC
o
t
AUC
o
∞
ot30%, t50%, t90%
2. Kinetic parameters
oDissolution rate constant
oDissolution half life
2. Pharmacokinetic parameters
oAbsorption & elimination rate constant & half life
3. Percent drug dissolved time profile
oPercent drug dissolved at time t
3. Percent drug absorbed time profile
4. Statistical moment analysis
o MDT
4. Statistical moment analysis
oMRT, MAT

36. 3.DIRECT, DIFFERENTIAL- EQUATION- BASED
in-vitro-in-vivo correlation (IVIVC) method = a novel method
▫A new, differential equation-based in-vitro-in-vivo correlation (IVIVC) method is
proposed that directly relates the time-profiles of in-vitro dissolution rates and
in -vivo plasma concentrations by using one- or multi- compartment
pharmacokinetic models and a corresponding system of differential
equations.
▫The rate of in-vivo input is connected to the rate of in-vitro dissolution through
a general functional dependency that allows for time scaling and time shifting.
A multiplying factor that accounts for the variability of absorption conditions
as the drug moves along is also incorporated.
▫Two data sets incorporating slow-, medium-, and fast-release formulations were
used to test the applicability of the method, and predictive powers were
assessed with a leave-oneformulation- out approach. All fitted parameters
had realistic values, and good or acceptable fits and predictions were
obtained as measured by plasma concentration mean squared errors and
percent AUC errors. Introduction of step-down functions that account for the
transit of the dosage form past the intestinal sites of absorption proved useful.
▫By avoiding the integral transforms used in the existing deconvolution –
or convolution based IVIVC models, the present method can provide
increased transparency, improved performance, and greater modelling
flexibility
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37. 37
IVIVR (In vitro-in vivo relationship)
•One possible substitution for IVIVC is IVIVR, with "R" denoting "relationship."
•Hence, IVIVR need not be limited to straight-line relationships, which generally
fails for IR products.
•This IVIVR analysis has been applied to several formulations of metoprolol,
piroxicam, and ranitidine.
•This indicated that one intent of IVIVR should be to learn about the relative
contribution of dissolution to a product's overall absorption kinetics.
WHATS IN STORE FOR THE FUTURE

38. APPLICATIONS OF IVIVC
A.IVIVC IN DRUG DELIVERY
a.EARLY STAGES OF DRUG DELIVERY TECHNOLOGY DEVELOPMENT
b.FORMULATION ASSESSMENT
c.DISSOLUTION SPECIFICATIONS
d.FUTURE BIOWAIVERS : For minor formulation and process changes
e.IVIVC PARENTERAL DRUG DELIVERY :
CAUSES OF FAILURE OF PARENTERAL IVIVC…
I.Burst Release
II.Potent Drugs & Chronic Therapy
III.Limited volume of tissue fluids and Area of absorption at the site of
administration, unlike following the oral route of administration.
Therefore, it is very difficult to specify the in vitro dissolution
conditions that reflect the observed differences in the in vivo plasma
profiles corresponding to the in vitro release profiles.

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39. B.NEW IVIVC APPLICATIONS
a.IVIVC FOR TRANSDERMAL ESTRADIOL SYSTEMS (Novel pharmaceuticals)
b.WHY IVIVC FAIL FOR IMMEDIATE RELEASE DOSAGE FORM
c.DISSOLUTION SIMULATORS
I.Gronings model
II.Sartorius dissolution simulator
III.Sartorius membrane filter solubility simulator
IV.Sartorius membrane filter absorption simulator
39
DISSOLUTION SIMULATORS
In order to enhance the capability of in vitro dissolution as a predictor of the in vivo
behavior of dosage forms. But many of these attempts required highly complex and
expensive apparatus with questionable advantage over traditional systems.
1.Gronings model:-
•It consists of two interconnecting flow through cells and a reservoir for the
dissolution
medium, all contained in a constant temperature water bath.
•The dosage form disintegrates in the gastric part of the model and some of the
drug
particles are continuously pumped into the intestinal part.
•During an experiment the cells are rotated by a slow speed electric motor.
Unlike
conventional dissolution apparatus it gave good IVIVC.

40. GLASS BEADS
SINTERED GLASS FILTER
AXIS OF ROTATION
SINTERED GLASS FILTER
POROUS PLASTIC
32/37
•Good IVIVC for all Nitrofurantoin tablets & capsules tested.
GRONINGS MODEL

41. WHY IVIVC FAIL FOR IMMEDIATE RELEASE DOSAGE FORM
•For Level A analysis, the fraction drug absorbed (Fa) is plotted against the fraction
drug dissolved (Fd). The fraction drug absorbed profile is obtained by
deconvoluting the plasma profile. Deconvolution is essentially a back calculation
to answer the question: "What must the drug absorption profile have been, given
the plasma profile?“
•A statistic from Level A analysis is r, the correlation coefficient. Its square r2,
ranges from zero to one and is a measure of the strength of relationship between
Fa against Fd. Often, results with sufficiently large r2 (e.g. greater than 0.9) yielded
"a (successful) correlation." An r2 value that was too low resulted in a "no
correlation" conclusion.
•Only products with dissolution rate-limited absorption (and with complete
absorption) can be expected to exhibit a Level A plot with a slope of one and zero
intercept, immediate release products will "fail" the Level A method.
41

42. IMPORTANT QUESTIONS
1.Explain IVIVC & IVIVR. Detail the methods for
establishing IVIVC. 05 Note:- 3 times in board
2.Give the factors affecting IVIVC. 05
3.What factors are affecting the development of
predictable IVIVC? 05
4.What is IVIVC? What are the criteria, objective and
need for IVIVC? What are the levels for correlation?
Why it fails for immediate release dosage forms? 06
5.What are the objectives of IVIVC? Describe different
levels of correlation for IVIVC. 05
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43. REFERENCES
•Guidance for Industry; Extended Release Oral Dosage Forms: Development, Evaluation,
and Application of In Vitro/In Vivo Correlations. www.fda.gov/cder/guidance/index.htm
•IVIVC: An Important Tool in the Development of Drug Delivery Systems; Gangadhar
Sunkara, PhD, and Dakshina M. Chilukuri, PhD.
http://www.drugdeliverytech.com/cgi-bin/articles.cgi?idArticle=144
•Dissolution, Bioavailability and Bioequivalence by Hamed M. Abdou, Mack Publishing
House.
•IVIVC Vs IVIVR; James E. Polli, Ph.D.
http://www.dissolutiontech.com/DTresour/800Articles/800_art1.html
•In Vitro–In Vivo Correlation: Importance of Dissolution in IVIVC; J-M. Cardot, E. Beyssac,
and M.Alric. Dissolution Technologies | FEBRUARY 2007
•IVIVC: Methods and Applications in Modified-Release Product Development; Harald Rettig
and Jana Mysicka. Dissolution Technologies | FEBRUARY 2008.
•Journal Metadata Search: Pharmaceutical Press - Journal of Pharmacy and Pharmacology
55(4); 495 (2003)
•Pharmaceutical dissolution testing, Umesh V. Banakar
•Dissolution, bioavailability & bioequivalence, Hamed M. Abdou.
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44. Ph. No. :- [phone]
Address:- 44, Assiyana Society;
Dugarvada Road,
Taluko & City : Modasa
State: Gujarat
Country: India
Email: [email protected]
BEST OF LUCK TO ALL . . . . . . . . . .
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