SUSTAINED RELEASE DRUG DELIVERY SYSTEM : CURRENT ADVANCE IN

MATRIX TABLET
INTRODUCTION :

Delivery of a pharmaceutical agent to the systemic circulation and consequently tothe site of
action to produce the desired pharmacological effect is the ultimate goal ofdrug delivery.Drugs
are most frequently taken by oral administration. Although a few drugs taken uncomplicated,
convenient, and safe means of administering drugs. Drugs are administered by the oral route in a
variety of pharmaceutical forms. The most popular are tablets, capsules, suspensions, and various
pharmaceutical solutions. Briefly, tablets are solid dosage forms prepared by compression or
molding that contains medicinal substances In recent years, modified release has come into
general use to describe dosage forms having drug-release features based on time, course, and/or
location that are designed to accomplish therapeutic or convenience objectives not offered by
conventional or immediaterelease forms. Drug products that provide extended or sustained
release (SR) first appeared as a major new class of dosage form in the late 1940s and early 1950s
. Over the years, many terms (and abbreviations), such as sustained release (SR), sustained action
(SA), prolonged action (PA), controlled release (CR), extended release (ER), timed release (TR),
and long acting (LA), have been used by manufacturers to describe product types and features.1

SUSTAINED RELEASE DOSAGE FORM :

The term "sustained release" is known to have existed in the medical and pharmaceutical
literature for many decades. It has been constantly used to describe a pharmaceutical dosage
form formulated to retard the release of a therapeutic agent such that its appearance in the
systemic circulation is delayed and/or prolonged and its plasma profile is sustained in duration.
The onset of its pharmacologic action is often delayed, and the duration of its therapeutic effect
is sustained. The term "controlled release," on the other hand, has a meaning that goes beyond
the scope of sustained drag action. It also implies a predictability and reproducibility in the drug
release kinetics, which means that the release of drag ingre-dient(s) from a controlled-release
drug delivery system proceeds at a rate profile that is not only predictable kinetically, but also
reproducible from one unit to another.2
Matrix system is widely used for the purpose of sustained release. It is the release system which
prolongs and controls the release of the drug that is dissolved or dispersed. In fact, a matrix is
defined as a well-mixed composite of one or more drugs with gelling agent i.e. hydrophilic
polymers. 3 Introduction of matrix tablet as sustained release has given a new breakthrough for
novel drug delivery system in the field of Pharmaceutical technology. Under gastric pH
conditions, matrix tablet slowly erodes. Two mechanisms are operative, either of which is zero-
order erosion and decreasing surface area, and dissolution of coated particles. The result in the
ability to control active pharmaceutical ingredient‟s blood level‟s in a narrow range, above the
minimum effective level and below toxic level.4
ADVANTADES OF SUSTAINED RELEASE DOSAGE FORM :
 Frequency of drug administration is reduce
 Compliance of patient improve and can be made more convenient as well
 The blood level oscillation characterstics of multiple dosing od conventional dosage form is
reduce
 Better control of drug absorbtion can be attained
 Total amount of drug administered can be reduced thus maximizing availability with
minimum dose
 The safety margin of high potency drug can be increased
 The incidence of both local and systemic adverse side effect can be reduce in sensitive
patient
 Increase reliability of therapy .
DISADVANTAGES OF SUSTAINED RELEASSE DOSAGE FORM:

 Medication does not permit the promot termination of therapy ,significant advers effect are
noted .
 Less flexibility in adjusting dosage regimen
 Economic factors must also be assesd ,more costely process and equipment (5)

BIOPHARMACEUTICAL PROPERTIES OF DRUG FOR SUSTAINED RELEASE

DOSAG FORM

Not all drugs are suited for formulation into sustained release products and not all medical
conditions require treatment with such a product. The drug and the therapeutic indication must
be considered jointly in determining whether or not to develop a sustained release dosage form.
  Drug should have a high potency and low therapeutic dose the typical weight of tablet
between 200-1000mg
 Drug should have large therapeutic range
 Drug with high solubility absorbed during the whole gastrointestinal passage absorbtion
can controlled by sustained the drug release by the slow dissolution
 A biological half life between approximetly 2-8 hours.(5)
 Atomic size ought to be beneath of 1000 Dalton.
 Aqueous solvency ought to be in excess of 0.1 mg/ml for pH 1 to pH 7.8.
 The partition coefficient ought to be high.
 Absolute bioavailability ought to be at least 75% or more.
 Absorption rate constant (Ka) ought to be higher than discharge rate. Apparent volume of
distribution (Vd) ought to be substantial.
 Total clearance ought not to rely upon dosage.
 Elimination rate constant are required for design and therapeutic concentration (Css) ought
to be low and smaller (Vd)
CLASSIFICATION OF SUSTAINED RELEASE SYSTEM 32 braham
The controlled release system for oral use are mostly solids and based on dissolution, diffusion
or a combination of both mechanism in the control of release rate of drug.
Depending upon the manner of drug release three systems are classified as follows:
1. Continuous Release systems
2. Delayed transit and controlled release systems
3. Delayed release system.
1.Continuous release system :
Continuous release systems release the drug for a prolonged period of time along the entire
length of gastrointestinal tract with normal transit of the dosage form. The various system under
this category are as follow:
A. Diffusion controlled release system
B. Dissolution controlled release system
C. Dissolution and diffusion controlled release system
D. Ion exchange resin drug complexes
E. pH -independent formulation
F. Osmotic pressure controlled systems
A.Diffusion controlled release system :
It is a major process for absorption in which no energy required. .the drug molecules diffuse
from higher concentration to lower concentration until equilibrium is attained and it is directly
proportional to the concentration gradient across the membrane. The drug release rate is never
zero order since the diffusional path length increase with time as the insoluble matrix is
gradually depleted of drug.. The two types of diffusion-controlled release are:
1. Matrix diffusion controlled systems
2. Reservoir devices 32
B.Dissolution-controlled release systems :41
Sustain release oral products employing dissolution as the rate limiting step are the principle
involves in this system. Dissolution-controlled release can be obtained by slowing the dissolution
rate of drug in GI medium, incorporating the drug in an insoluble polymer and coating drug
particles or granules, with polymeric material of varying thickness.
(a) Encapsulation Dissolution Controlled Systems
(b) (b) Matrix Dissolution Controlled System
B. and diffusion controlled release systems :42
In this systems the drug core is encased in a partially soluble membrane. Pores are thus created
due to dissolution of parts of membrane which permit entry of aqueous medium into the core and
hence drug diffusion of dissolved drug out of the system.
C.Ion exchange resin-drug complexes :43
It is based on formulation of drug resin complex formed when ionic solution is kept in contact
with ionic resins. Drug from this complex gets exchanges in gastrointestinal tract and release
with Na+ and Cl present in gastrointestinal tract. This system utilize resin compound of insoluble
cross linked polymer.
D.Ph independent controlled release system44
The drug are either weak acid or weak base, the release from sustained release dosage
formulation is pH dependent. However buffer such as salt of citric acid, aminoacid, tartaric acid
can be added in the formulation to help to maintain to constant pH thereby retarding pH
independent drug release. Sustained release formulation is prepared by a basic or acidic drug
mixing in one or more buffering agent, granulation with appropriate excipients and coating with
gastrointestinal fluid permeable film forming polymer. When gastrointestinal fluid permeates
through the membrane the buffering agent adjust the fluid inside to suitable constant pH thereby
rendering a constant rate of drug release

FACTORS INFLUENCING ORAL SUSTAINED RELEASE:

Dosage Form Design
Two factors involved in oral sustained-release dosage form design.
A. Biological Factors
B. Physiochemical Factors
Biological Half Life33
The basic goal of an oral Sustained Release product is to maintain therapeutic blood levels over
an extended period of time. To achieve this, drug must enter the circulation at approximately the
same rate at which it is eliminated. The elimination rate is quantitatively described by the half-
life (t1/2).Compounds with short halflife are generally are excellent candidate for sustained
release formulation. in general, compounds with long half-life, more than 8 hours are also
generally not used in sustained release dosage form , since their effect is already sustained.
Absorption34
a sustained formulation depends upon Rate of absorption amd release rate constant of the drug
from the dosage form, and the absorption is limited to intestine for the drugs that are absorbed by
active transport Since control on the delivery system is the main purpose of forming a SR
product, it is necessary that the rate of release is much slower than the rate of absorption. If we
assume that the transit time of drugs in the GI tract is about 8-12 hours, the maximum half-life
for absorption should be approximately 3-4 hours; otherwise, before drug release is complete the
device will pass out of the potential absorptive regions 34
2. Metabolism35
The metabolic transfer to a drug is to be considered before converting into another form. as long
as the location, rate, and extent of metabolism are known a successful sustained release dosage
form can be developed.
3. Distribution
Drugs with high volume of distribution, which control the rate of elimination of the drug, are
reduced candidate for oral control release drug delivery system e.g. Chloroquine
Margin of Safety
As we identify more considerably extensive the value of therapeutic index for protect is the drug.
Drugs with a lesser amount of therapeutic index customarily reduced candidate for formulation
of oral control release drug distribution system due to technological direct of control over release
rates
Protein Binding
The Pharmacological response of drug depends on unbound drug concentration drug rather than
total concentration and all drug bound to some extent to plasma and or tissue proteins. Proteins
binding of drug play a significant role in its therapeutic effect regardless the type of dosage form
as extensive binding to plasma increase biological half-life and thus sometimes SR drug delivery
system is not required for this type of drug.
B Physicochemical Factors Influencing Release From Matrix Tablet
Dose size 36
For orally administered systems, there is an upper limit to the bulk size of the dose to be
administered. In general, a single dose of 0.5-1.0g is considered maximal for a conventional
dosage form. This also holds for sustained release dosage form. Compounds that require large
dosing size can sometimes be given in multiple amounts or formulated into liquid systems.
Another consideration is the margin of safety involved in administration of large amount of a
drug with a narrow therapeutic range.
Ionization, pka and aqueous solubility: 37
Most drugs are weak acids or bases. Since the unchanged form of a drug preferentially permeates
across lipid membranes, it is important to note the relationship between the pka of the compound
and the absorptive environment. Presenting the drug in an unchanged form is advantageous for
drug permeation. Unfortunately, the situation is made more complex by the fact that the drug’s
aqueous solubility will generally be decreased by conversion to unchanged form. Delivery
systems that are dependent on diffusion or dissolution will likewise be dependent on the
solubility of the drug in aqueous media. These dosage forms must function in an environment of
changing pH, the stomach being acidic and the small intestine more neutral, the effect of Phone
the release process must be defined. Compounds with very low solubility .
Particle Size and Shape: 38
Other factors, such as the particle size and shape of soluble drugs, also influence drug release,
mainly because of the diffe ence in effective surface area and, thus, the intrinsic dissolution rate
found decreased oxazepam dissolution rates with an increase in drug particle size, at a constant
volume fraction of water will be high towards the erosion front and drug : HPMC K100M ratio.
These findings were in accordance with the results reports for HPMC K15M matrices containing
indomethacin.

Partition coefficient
Bioavailability of a drug is largely influenced by the partition coefficient, as the biological
membrane is lipophilic in nature transport of drug across the membrane largely depends upon the
partition coefficient of the drug. Drugs having low partition coefficient are considered as poor
candidate for the sustain release formulation as it will be localized in the aqueous phase eg:
Barbituric acid and vice a versa.
Drug stability
When drugs are orally administered, they come across acid-base hydrolysis and enzymatic
degradation. In this case, if the drug is unstable in stomach, drug release system which provides
medication over extended period of time is preferred, whereas in contrast the drug unstable in
intestine will face problem of less bioavailability 40

MATRIX TABLET
To develop the sustained release dosage form is the direct compression of blend of drug, the
retardant. Conversely, a retardant drug blend may be granulated before compression. Matrix
tablets can be considered as the commercially sustained action dosage form that involves
minimum processing variables, employs conventional facilities, and accommodates drugs in
large doses.(7)
Amongst extended release formulations, matrix technology is most widely used drug delivery
system due to many advantages such as desired release profile for wide therapeutic drug
category, dose and solubility, simple and cost-effective manufacturing process, robust and ease
of drug release profiles from polymeric systems. The matrix system involves the homogenous
dispersion of drug particles in either a hydrophobic or hydrophilic
polymer matrix; therefore, the physicochemical nature of the matrix controls the release rate
of the drug and determines the release mechanism(8)
Advantages of matrix tablet :
• Easy to manufacture.
• Cost effective.
• Improved patient compliance.
• Sustained release formulations avoid the high blood concentration.
• Reduce drug toxicity by slowing down drug absorption.
• Enhanced drug stability in GI milieu.
• Minimize the local and systemic side effects.
• No see-saw fluctuations in plasma drug concentration profile.
• Less amount of drug is required.
• Temporal effects can be provided. e.g. morning relief of arthritis through bed time dosing
Disadvantages of matrix tablets:
• Matrix needs to be removed after drug release.
• Costly in comparison to conventional dosage form.
• Presence of food and gut transition time can affect the release rate (9)

CLASSIFICATION OF MATRIX TABLET

1-On the basis of retardant material
2-on the Basis of porosity
3- On the basis of the way of matrix preparations
Classification based on the characteristics of rate controlling material.
A-Hydrophillic type matrix 11
In thissystem, the rate controlling materials are water soluble and/or swellable. Matrix is a well
mixed composite of one or more drugs with gelling agent. Commonly available hydrophilic
polymers include:The polymers used in the preparation of hydrophilic matrices are divided into
three broad groups as follow:
a) Cellulose derivatives: Hydroxyethylcellulose, Hydroxypropymethylcellulose(HPMC)
25,100,4000and15000cps, sodium carboxy methyl cellulose and Methylcellulose 400 and 4000
cps.
b) Non-cellulose natural or Semi-synthetic polymers: Agar-agar, Carob Gum, Alginates,
Polysaccharides of mannose and Galactose, Chitosan and Modified starches.
c) Acrylic acid polymer: Carbopol 934 Other hydrophilic materials used for preparation of
matrix tablet are Alginic acid, Gelatin and Natural gums.(11)
B-Hydrophobic matrices 12
The concept of using hydrophobic or inert material as matrix tablet was first introduced in 1959.
In this method to obtain a sustained release from an oral dosage form, drug is mixed is mixed
with a hydrophobic or inert polymer and then compressed to a tablet. Sustained released is
obtained because the dissolving drug is diffused through a network of channels that exist
between compacted polymer particles. This is the only system where the use of polymer is not
essential to provide controlled drug release, although insoluble polymers have been used. As the
name suggests the primary rate controlling component of hydrophobic matrix are water insoluble
in nature such as waxes, fatty acids, glycerides and polymeric materials such as methyl cellulose,
ethyl cellulose to modulate the release rate of drug.(12)
Release is usually delayed because the dissolved drug has to diffuse through capillary network
between the compacted polymer particles. Plastic matrix tablets, in which the active ingredient is
embedded in a tablet with coherent and porous skeletal structure, can be easily prepared by direct
compression of drug with plastic materials provided the plastic material can be comminuted or
granulated to desired particle size to facilitate mixing with the drug particle. In order to granulate
for compression into tablets, the embedding process may be accomplished by,
1) The solid drug which is mixed with plastic powder and kneaded with a solution of the same
plastic material or other binding agent in an organic solvent and then granulated.
2) An organic solvent which is used for dissolution of drug in the plastic and granulated upon
evaporation of the solvent.
3) Using latex or pseudo latex as granulating fluid which is used to granulate the drug and plastic
masses. Example: Polyvinyl chloride, Ethyl cellulose, Cellulose acetate and Polystyrene.(11-12)
C) Lipid Matrices13
These matrices are prepared by the lipid waxes and related materials. Drug release from such
matrices occurs through both pore diffusion and erosion. Release characteristics are therefore
more sensitive to digestive fluid composition than to totally insoluble polymer matrix. Carnauba
wax in combination with stearyl alcohol or stearic acid has been utilized for retardant base for
many sustained release formulation.13
D) Biodegradable Matrices[15]
These consist of the polymers which comprised of monomers linked to one another through
functional groups and have unstable linkage in the backbone. They are biologically degraded or
eroded by enzymes generated by surrounding living cells or by nonenzymetic process in to
oligomers and monomers that can be metabolized or excreted. Examples are natural polymers
such as proteins and polysaccharides; modified natural polymers; synthetic polymers such as
aliphatic poly (esters) and poly anhydrides.
E) Mineral Matrices14
These consist of polymers which are obtained from various species of seaweeds. Example is
Alginic acid which is a hydrophilic carbohydrate obtained from species of brown seaweeds
(Phaephyceae) by the use of dilute alkali.(14)
2-on the basis of their porosity.
A. Macro-porous Systems:
In such systems the diffusion of drug occurs through pores of matrix which are of size range 0.1
to 1 μm. This pore size is larger than diffusion molecule size
B. Micro-porous System:
Diffusion in this type of system occurs essentially through pores. For micro porous systems, pore
size ranges between 50 – 200 A°, which is slightly larger than diffusion Molecules size.
C. Non-porous System:
Non-porous systems have no pores and the molecules diffuse through the network meshes. In
this case, only the polymeric phase exists and no pore phase is present. 4. Hybrid system: System
in which the drug in matrix of release retarding material is further coated With increase
controlling polymer membrane.(15)
3-On the basis of the way of matrix preparations

A. Floating matrix system 25

In this type of matrix system, the bulk density of the matrix is lower than the gastric fluid in the
stomach. After creating buoyancy in the stomach, the release of drug molecules from the matrix
can occur slowly, which prolongs gastric residence time and thereby increases the bioavailability
of fast release drug molecules. 25
B. pH sensitive matrix system26
In this type of matrix system, an enteric coating of the matrix system can provide protection for
the drug from the harsh acidic media of the stomach. Thus, low pH sensitive drug molecules can
reach the small intestine and colon safely. This matrix system works by releasing the enteric
coated drug at a specifically high pH value in the GIT, where drug absorption can occur in the
right location. PH sensitive polymers such as HPMC- phthalate or cellulose acetate phthalate can
be used in this type of matrix system. 26
C. Mucoadhesive matrix system 27
Mucoadhesive matrix systems are designed to enable prolonged retention in the gastric region
for several hours and hence significantly prolong the gastric residence time of drugs. Prolonged
gastric retention improves bioavailability. In this type of matrix system, the release of the drug is
controlled over a period of time. The targeted tissues can be gastrointestinal, buccal, ocular,
nasal, respiratory, rectal, urethral and vaginal tissues. In addition, this type of matrix system can
be applied to any mucosal tissue in the body. The used materials in this system are swellable
hydrophilic polymers which can interact with the glycoproteins being available in the mucous
layer of the gut.27
MASRX and COSRX Sustained-Release Technology Masrx Technology 16
The objective is to assess factors affecting drug release from guar-gum-based once-daily matrix
sustained-release formulations (MASRx). The tablets were designed to hydrate completely into
the tablet core. In the process, the tablet core expanded and released the drug in a
sustainedrelease manner.
COSRx Technology Formulations base on constant sustained-release matrix (COSRx)
technology can also be developed using guar gum as a major rate-controlling polymeric material.
Depending on the solubility of the drug, low- or high-viscosity guar gum can be use. The
formulation involves a guar-gum-base tablet and a combination of water-soluble and water-
insoluble polymeric tablet coat. When the tablet is placed in a dissolution medium, there is slow
diffusion of water through the polymeric wall leading to swelling and gelations of the guar
gum/drug core. As the hydration a progress, the tablet continues to swell until the wall breaks,
forming a sandwich-like structure. The release of drug proceeds primarily out of the sides of the
tablet as it passes through the intestinal tract. The tablets provide a nearly zero-order drug release
following a programmed period of delayed drug release.(16)
POLYMERS USED IN THE MATRIX17
The polymers most widely used in preparing matrix system include both hydrophilic and
hydrophobic polymers.
(A) Hydrophilic Polymers: Hydroxyl propyl methyl cellulose (HPMC), hydroxyl propyl
cellulose(HPC), hydroxyl ethyl cellulose (HEC), Xanthan gum, Sodium alginate, poly(ethylene
oxide), and cross linked homopolymers and co-polymers of acrylic acid.
(B) Hydrophobic Polymers: This usually includes waxes and water insoluble polymers in their
formulation.
(C) Waxes: Carnauba wax, bees wax, candelilla wax, micro crystalline wax, ozokerite wax,
paraffin waxes and low molecular weight polyethylene.
(D) Insoluble polymers: ammoniomethacrylate copolymers (Eudragit RL100, PO, RS100, PO),
ethyl cellulose, cellulose acetate butyrate, cellulose acetate propionate and latex dispersion of
meth acrylic ester copolymers.(17)

METHODS OF PREPARATION 23 24
1. Direct Compression
In this process, powdered materials are compressed directly without changing the properties of
the drug like physical and chemical.
2. Wet Granulation
In this method weighed quantities of drug and polymer are mixed with sufficient volume of the
granulating agent. After enough cohesiveness was obtained, the mass is sieved through 22/44
mesh. The granules are dried at 40°C and after that kept in a desiccator at room temperature.
Once the granules dried are retained on 44 meshes were mixed with 15% of fines. Lubricants and
Glidants are added and the tablets are compressed using a tablet compression machine[38].
3. Melt Granulation
This substance can be added in the molten form over the substrate, which is then heated above its
melting point. In melt granulation, meltable substance act as liquid binding agent and hence does
not require the use of organic solvents. Various lipophilic binders such as Glyceryl
Palmitostearate were used in melt granulation technique[39].
Hot-Melt Extrusion Process 39
In the hot-melt extrusion process, a mixture of the active ingredients, the thermoplastic polymers
and other processing aids is fed into the barrel of the extruder through the hopper. The materials
are transferred inside the heated barrel by a rotating screw. The materials melt at elevated
temperatures and the molten mass is continuously pumped through the die attached at the end of
the barrel. Depending upon the dimensions of the die cylinders, films can also be produced from
the extruder.

DRUG RELEASE FROM MATRIX

A matrix system consists of active and inactive ingredients, which are homogeneously dispersed
and mixed in the dosage form. According to the materials used, the matrix systems have different
mechanisms toward the controlled action. The release from matrix type formulations is governed
by Fick's first law of diffusion.( 19)
Drug Release from Matrix System [20,21]
Drug in the outside layer exposed to the bathing solution is dissolved first and then diffuses out
of the matrix. This process continues with the interface between the bathing solution and the
solid drug moving toward the interior. It follows that for this system to be diffusion controlled,
the rate
of dissolution of drug particles within the matrix must be much faster than the diffusion rate of
dissolved drug leaving the matrix. Derivation of the mathematical model to describe this system
involves the following assumptions:
a) A pseudo-steady state is maintained during drug release;
b) The diameter of the drug particles is less than the average distance of drug diffusion through
the matrix;
c) The bathing solution provides sink conditions at all times.
The release behavior for the system can be mathematically described by the following equation:
DM/Dh = Co. Dh - Cs/2………………………………………………….(I)
Where;
DM = Change in the amount of drug released per unit area
Dh = Change in the thickness of the zone of matrix that has been depleted of drug
Co = Total amount of drug in a unit volume of matrix
Cs = Saturated concentration of the drug within the matrix.
Additionally, according to diffusion theory:
DM = (Dm. Cs / h).Dt …………. ………………………………………….(II)
Where;
Dm = Diffusion coefficient in the matrix.
h = Thickness of the drug-depleted matrix
Dt = Change in time
By combining equation I and equation II and integrating:
M = [Cs. Dm. (2Co−Cs). t] ½ ……………………………………………. (III)
When the amount of drug is in excess of the saturation concentration, then:
M = [2Cs. Dm. Co. t] ……........................................................................... (IV)
Equation III and equation IV relate the amount of drug release to the square-root of time.
Therefore, if a system is predominantly diffusion controlled, then it is expected that a plot of the
drug release vs. square root of time will result in a straight line. Drug release from a porous
monolithic matrix involves the simultaneous penetration of surrounding liquid, dissolution of
drug and leaching out of the drug through tortuous interstitial channels and pores. The volume
and length of the openings must be accounted for in the drug release from a porous matrix:
M = [Ds.Ca.p/T. (2Co – p.Ca) t] ½………………………………………………..(V)
Where:
p = Porosity of the matrix
t = Tortuosity
Ca = solubility of the drug in the release medium
Ds = Diffusion coefficient in the release medium.
T = Diffusion path length.
For pseudo steady state, the equation can be written as:
M = [2D.Ca .Co (p/T) t] ½……………………………………………………………(VI)
The total porosity of the matrix can be calculated with the following equation:
p = pa + Ca/ ρ + Cex/ ρex………………………………………………………....(VII)
Where:
p = Porosity
ρ = Drug density
pa = Porosity due to air pockets in the matrix
ρex = Density of the water soluble excipients
Cex = Concentration of water soluble excipients.
For the purpose of data treatment, equation VII can be reduced to:
M = k. t ½ .…………………………………………………………………………… (VIII)
Where
K is a constant, so that the amount of drug released versus the square root of time will be linear,
if the release of drug from matrix is diffusion-controlled. If this is the case, the release of drug
froma homogeneous matrix system can be controlled by varying the following parameters:
 Initial concentration of drug in the matrix
 Porosity
 Tortuosity
 Polymer system forming the matrix
 Solubility of the drug.

General Mechanism of drug release 22

Alderman (1984) describes a gel layer being formed around a tablet (Fig. 6); this is because
when hydrophilic matrices are immersed in aqueous media i.e. Gastro-intestinal fluids, the
polymer hydrates and swells resulting in an increase in size. After some time the matrix dissolves
or erodes allowing drug release . The soluble portion of the drug is released by the process of
diffusion through the gel layer while the insoluble portion is released through tablet erosion .
Studies have shown that drug release from swellable hydrophilic matrices is dependent on the
thickness of the hydrated layer that is formed during polymer hydration. The degree of swelling
determines the rate of drug release; the thicker the gel layer, the slower the rate of drug release .

EVALUATION TEST FOR SUSTAINED RELEASE MATRIX TABLETS

Weight variation 28
Weigh and dissolve ethyl cellulose 95% in ethanol to prepare 2% W/W solution,Mix the sifted
materials for 5mts in a poly bag and the each Venlafaxine hydrochloride weight 84.86mg equal
to venlafaine 75mg are shown Table 1.

The test ensures that all the tablets in each batch are of same potency, within reasonable limits.
According to the USP weight variation test. The specification of the weight variation limits as
per USP .

Drug content
A total of l0 tablets are triturated using mortar and pestle. A quantity of powder weighed
equivalent to 84.86 mg of drug was transferred to 100 ml of standard flask and volume made up
to 100 ml with purified water.
Hardness test
A total of 10 tablets from each batch were used and the hardness was expressed in kg/mm2.
Friability
Friability test was performed to assess the effect of friction and shock which may often cause
tablets to chip, cap, or break.
Swelling behaviour of controlled release matrix tablets:29
The extent of swelling was measured in terms of % weight gain by the tablet. The swelling
behavior of formulations were studied. One tablet from each formulation was kept in a Petri dish
containing pH 7.4 phosphate buffer. At the end of 1 h, then for 2 h, the tablet was withdrawn,
kept on tissue paper and weighed and the process was continued till the end of 12 h. The %
weight gain by the tablet was calculated by formula.
S.I = {(Mt-M0) / M0} X 100
Where,
S.I = swelling index,
Mt = weight of tablet at time (t) and
Mo = weight of tablet at time t = 0.
In-vitro drug release rate30
Formulated tablet were subjected to invitro dissolution study using USP type І / ІІ apparatus
(paddle) at 100 rpm with temperature of water bath maintain at 37±0.5oc. Dissolution was
carried in 900 ml simulated gastric fluid for 2 hrs and for further 8 hrs in simulated intestinal
fluid. The release of different drugs at different time interval was measured at particular
wavelength by U.V- visible spectrophotometer