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Modern Pharmaceutics

Higuchi and Peppas Plot






Introduction to Higuchi plot:

 Ideally, controlled drug-delivery systems should deliver the drug at a
controlled rate over a desired duration.

 The primary objectives of the controlled drug-delivery systems are to ensure
safety and to improve efficacy of drugs, as well as to improve patient

 Of the approaches known for obtaining controlled drug release, hydrophilic
matrix is recognized as the simplest and is the most widely used.
Hydrophilic matrix tablets swell upon ingestion, and a gel layer forms on
the tablet surface. This gel layer retards further ingress of fluid and
subsequent drug release.


 It has been shown that in the case of hydrophilic matrices, swelling and
erosion of the polymer occurs simultaneously, and both of them contribute
to the overall drug-release rate.

 It is well documented that drug release from hydrophilic matrices shows a
typical time-dependent profile (ie, decreased drug release with time because
of increased diffusion path length). This leads to first-order release kinetics.

 In 1961, Higuchi tried to relate the drug release rate to the physical constants
based on simple laws of diffusion.

 Higuchi was the first to derive an equation to describe the release of a drug
from an insoluble matrix as the square root of a time-dependent process
based on Fickian diffusion.


Higuchi’s hypothesis includes:

 Initial drug concentration in the matrix is much higher than
drug solubility.

 Drug diffusion takes place only in one dimension.

 Drug particles are much smaller than system thickness.

 Matrix swelling and dissolution are negligible.

 Drug diffusivity is constant.

 Perfect sink conditions are always attained in the release



Higuchi plot representation:



Higuchi describes the drug release as a
diffusion process based on Fick’s law, square
root time dependent.

This model is useful for studying the release of
water soluble and poorly soluble drugs from
variety of matrices, including solids and


Korsmeyer-Peppas Model


Korsmeyer et al (1983) derived a simple relationship
which described drug release from a polymeric system.

To find out the mechanism of drug release, first 60%drug
release data were fitted in peppas model


Processes involved in Peppas Model

 There are several simultaneous processes considered in this

 Diffusion of water into the tablet

 Swelling of the tablet as water enters

 Formation of gel

 Diffusion of drug and filler out of the tablet

 Dissolution of the polymer matrix


Key Attributes:

 Key attributes of the model include:

 Tablet geometry is cylindrical

 Water and drug diffusion coefficients vary as
functions of water concentration

 Polymer dissolution is incorporated

 Change in tablet volume is considered



 The KORSEMEYAR AND PEPPAS empirical expression relates the function of time
for diffusion controlled mechanism.

 It is given by the equation :

Mt / Ma = Ktn


 Mt / Ma is fraction of drug released

 t = time

 K=constant includes structural and geometrical characteristics of the dosage form


 n= release component which is indicative of drug release mechanism

where ,

n is diffusion exponent.

 i. If n= 1 , the release is zero order

 ii. n = 0.5 the release is best described by the Fickian diffusion

 iii. 0.5 < n < 1 then release is through Anomalous diffusion 19


Assumptions based on model:

 The following assumptions were made in this model:

 The generic equation is applicable for small values of t
or short times and the portion of release curve where
Mt/M ∞ < 0.6 should only be used to determine the
exponent n.

 Drug release occurs in a one dimensional way.

 The system’s length to thickness ratio should be at
least 10.


Peppas Plot

To study the release kinetics, data obtained from in vitro drug release studies
were plotted as log cumulative percentage drug release versus log time.



 This model has been used frequently to describe the drug release
from several modified release dosage forms.

 This equation has been used to the linearization of release data
from several formulations of microcapsules or microspheres

 Use to analyze the release of pharmaceutical polymeric dosage

 When the release mechanism is not known or when more than
one type of release phenomena could be involved.