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Polymers in Oral ControlledPolymers in Oral Controlled
Release Drug Delivery SystemsRelease Drug Delivery Systems
Y.RAMESH
M.PHARMACY, (DEPARTMENT OF PHARMACEUTICS)RAOS COLLEGE OF PHARMACY, NELLORE.
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Pharmaceutical PolymersPharmaceutical Polymers
Definition
Compounds formed by the joining ofsmaller, usually repeating, units linked bycovalent bonds.
These compounds form largemacromolecules called as polymers.
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Pharmaceutical PolymersPharmaceutical Polymers
Oral dosage forms are broadly divided
into Liquid and Solid forms
Suspensions and Tablets are commonly
formulated with various polymers
some times in combination to achieve
the desired product profile.
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Polymers in TabletsPolymers in Tablets
Conventional (IR) Tablets where
Polymers are employed as Binders
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Polymers in TabletsPolymers in Tablets
Controlled/Modified/Extended/Delayed
Release Tablets
where Polymers are employed as
Controlled Release agents -
Hydrophilic Cellulose Derivatives
Eudragit Matrix Formulations
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Commonly used Polymers in TabletsCommonly used Polymers in Tablets
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Hydrophilic Cellulose DerivativesHydrophilic Cellulose Derivatives
Hydrophilic matrices are most popular
Modified release oral dosage forms
Swellable polymers used to prolong drug
release
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Hydrophilic Cellulose DerivativesHydrophilic Cellulose Derivatives
HPMCs are of high interest due to their:
Good compression characteristics,including Direct Compression
Adequate swelling property, that allows
rapid external gel formation allowing CRof Drug
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Hydrophilic Cellulose DerivativesHydrophilic Cellulose Derivatives
Available in several substitution and
viscosity grades
Well characterized in compendia and
most of them have US GRAS status
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Compressed Cellulose ether systems as Swelling ControlledCompressed Cellulose ether systems as Swelling Controlled
SystemsSystems -- ROLE OF POLYMERSROLE OF POLYMERS
POLYMERS RELATED FACTOR IN CR
Volume change of the swellable matrixand countercurrent diffusion of the solvent
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Compressed Cellulose ether systems as Swelling ControlledCompressed Cellulose ether systems as Swelling Controlled
SystemsSystems -- ROLE OF POLYMERSROLE OF POLYMERS
PHOTO OF SWELLEN TABLET also FIG 1
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Compressed Cellulose ether systems as Swelling ControlledCompressed Cellulose ether systems as Swelling Controlled
SystemsSystems -- ROLE OF POLYMERSROLE OF POLYMERS
Erodible, swellable systems, where zero-order
release is achieved -
when the movements of the diffusing front (solid
drug-drug solution interface) and
the eroding front (rubbery polymer-solventinterface) are SYNCHRONIZED
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Compressed Cellulose ether systems as Swelling ControlledCompressed Cellulose ether systems as Swelling Controlled
SystemsSystems -- ROLE OF POLYMERSROLE OF POLYMERS
Solute release is governed by the penetration
velocity of the solvent (swelling front).
Constant release is observed when the solvent
penetration is much slower than drug diffusion
in the swollen gel (case 2, transport)
Thickness of the gel layer as a function of time,
rate of swelling, and velocity of the eroding front
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Compressed Cellulose ether systems as Swelling ControlledCompressed Cellulose ether systems as Swelling Controlled
SystemsSystems -- ROLE OF POLYMERSROLE OF POLYMERS
Gel thickness is proportional to the square
root of time as long as the swelling frontmoves more rapidly than the eroding front,
(but synchronization of both fronts may occur
leading to constant drug release)
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Compressed Cellulose ether systems as Swelling ControlledCompressed Cellulose ether systems as Swelling Controlled
SystemsSystems -- ROLE OF POLYMERSROLE OF POLYMERS
Third front i.e., diffusion front which is an
interface between still un-dissolved (solid) drug
and the dissolved drug in the gel layer.
Drug release is a function of the dissolved drug
gel layer that separates the diffusion front from
the erosion front.
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Compressed Cellulose ether systems as Swelling ControlledCompressed Cellulose ether systems as Swelling Controlled
SystemsSystems -- ROLE OF POLYMERSROLE OF POLYMERS
shows the relative positions of the three moving fronts in swellable
matrix.
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Compressed Cellulose ether systems as Swelling ControlledCompressed Cellulose ether systems as Swelling Controlled
SystemsSystems -- ROLE OF POLYMERSROLE OF POLYMERS
The diffusion front is present as long as
the concentration of the undissolved drug
exceeds its solubility in the swollen
polymer matrix.
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Compressed Cellulose ether systems as Swelling ControlledCompressed Cellulose ether systems as Swelling Controlled
SystemsSystems -- POLYMER CHARACTERISTICSPOLYMER CHARACTERISTICS
Release mechanism from compressed HPMC
are discussed earlier
However other cellulose derivatives such as
- Methyl Cellulose (MC)
- Hydroxyl ethyl cellulose (HEC) &- Hydroxy propyl cellulose (HPC)
have different drug release behavior.
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Compressed Cellulose ether systems as Swelling ControlledCompressed Cellulose ether systems as Swelling Controlled
SystemsSystems -- POLYMER CHARACTERISTICSPOLYMER CHARACTERISTICS
Physicochemical properties of six non-ionic
cellulose ethers are compared
varying by their substitution type (HPMC, MC, HEC,
and HPC) or
Degree of substitution (USP HPMC 2208, 2906, and
2910)
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Compressed Cellulose ether systems as Swelling ControlledCompressed Cellulose ether systems as Swelling Controlled
SystemsSystems -- POLYMER CHARACTERISTICSPOLYMER CHARACTERISTICS
Polymers of similar viscosity grades(4000-5000 mPas)
although not identical molecular masses they are
characterized by their hydrophilicity.
Phenylpropanolamine (PPA) HCL as water
soluble model drug
Used at various loadings.
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Compressed Cellulose ether systems as Swelling ControlledCompressed Cellulose ether systems as Swelling Controlled
SystemsSystems -- POLYMER CHARACTERISTICSPOLYMER CHARACTERISTICS
Compressed matrices made of pure
polymers and drugs were assessed fortheir
swelling,
erosion, and
release properties.
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Compressed Cellulose ether systems as Swelling ControlledCompressed Cellulose ether systems as Swelling Controlled
SystemsSystems -- POLYMER CHARACTERISTICSPOLYMER CHARACTERISTICS
Materials
HPMC 2208, 2906, 2910 (Methocel K4M,F4M, E4MCR)
HEC (Natrosol 250 M)
HPC (Klucel 99MF)
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Compressed Cellulose ether systems as Swelling ControlledCompressed Cellulose ether systems as Swelling Controlled
SystemsSystems -- POLYMER CHARACTERISTICSPOLYMER CHARACTERISTICS
Materials
All materials had moisture less than 5 %
Size fractions of less than 63 m were used
to minimize the lag time observed during drug
release with coarse fractions
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Compressed Cellulose ether systems as Swelling ControlledCompressed Cellulose ether systems as Swelling Controlled
SystemsSystems -- POLYMER CHARACTERISTICSPOLYMER CHARACTERISTICS
POLYMER MOLECULAR WEIGHT
DS Degree of Substitution
MS: Molar Substitution (HEC & HPC)
Nominal Viscosity
Grade Weight-Average Molecular Weight MW Molecular Weight of the Repeating Unit MO
Weight-Average Degree of Polymerization DPW
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Compressed Cellulose ether systems as Swelling ControlledCompressed Cellulose ether systems as Swelling Controlled
SystemsSystems POLYMER CHARACTERISTICSPOLYMER CHARACTERISTICS
POLYMER HYDROPHILICITY
Using hygroscopicity
COMPACT PREPARATION
Polymer and Drug ration 80:20 weight ratio, 500mg
directly compressed 10kN in 15-mm die using
hydraulic press equipped with flat-faced punches
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Compressed Cellulose ether systems as Swelling ControlledCompressed Cellulose ether systems as Swelling Controlled
SystemsSystems POLYMER CHARACTERISTICSPOLYMER CHARACTERISTICS
SWELLING AND FRONT MOVEMENTS
The position of the fronts upon water
penetration inside the tablets
The drug release behavior
Polymer dissolution
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Compressed Cellulose ether systems as Swelling ControlledCompressed Cellulose ether systems as Swelling Controlled
SystemsSystems POLYMER CHARACTERISTICSPOLYMER CHARACTERISTICS
SWELLING AND FRONT MOVEMENTS
Circular device (Bettini 33) allowing water to
enter only from the lateral side.
The cylindrical matrix is locked between two
transparent poly(methyl methacrylate) disks
and
the assembly is placed in USP 23 dissolution
apparatus 2.
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Compressed Cellulose ether systems as Swelling ControlledCompressed Cellulose ether systems as Swelling Controlled
SystemsSystems POLYMER CHARACTERISTICSPOLYMER CHARACTERISTICS
SWELLING AND FRONT MOVEMENTS
Paddle RPM 75 and 400ml Dissolution medium.
Methylene blue (0.004%) to improve visualization of the three
concentric circles corresponding to
Swelling
Diffusion and
Erosion
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Compressed Cellulose ether systems as Swelling ControlledCompressed Cellulose ether systems as Swelling Controlled
SystemsSystems POLYMER CHARACTERISTICSPOLYMER CHARACTERISTICS
POLYMER DISENTANGLEMENT CONCENTRATION
Water as medium, polymer dissolved is
estimated calorimetricaly
Mass balance is estimated by adding tablets
initial weight, released drug and dissolved
polymer. (dry weight of swollen tablets after
4hours of drying)
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Compressed Cellulose ether systems as Swelling ControlledCompressed Cellulose ether systems as Swelling Controlled
SystemsSystems POLYMER CHARACTERISTICSPOLYMER CHARACTERISTICS
POLYMER DISENTANGLEMENT CONCENTRATION
Matrix erosion is described as the
dissolution of the disentangled
macromolecules from the rubbery
polymer.
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Compressed Cellulose ether systems as Swelling ControlledCompressed Cellulose ether systems as Swelling Controlled
SystemsSystems POLYMER CHARACTERISTICSPOLYMER CHARACTERISTICS
POLYMER DISENTANGLEMENT CONCENTRATION
Polymer disentanglement occurs beyond acritical concentration Cd,
depending on the molecular weight of the
chains, and
on their conformation in a given solvent and
at a given temperature.
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Compressed Cellulose ether systems as Swelling ControlledCompressed Cellulose ether systems as Swelling Controlled
SystemsSystems POLYMER CHARACTERISTICSPOLYMER CHARACTERISTICS
POLYMER DISENTANGLEMENT CONCENTRATION
Cd is difficult to estimate accurately, hencethe coil overlap concentration C*p beyond
which polymer chain disentanglement
commences.
Overlap concentrations were obtained by low
shear viscometry
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Compressed Cellulose ether systems as Swelling ControlledCompressed Cellulose ether systems as Swelling Controlled
SystemsSystems POLYMER CHARACTERISTICSPOLYMER CHARACTERISTICS -- RESULTSRESULTS
POLYMER HYDROPHILICITY
Ability to absorb water vapor In increasing order
HPC MC < HPMC 2910 HPMC 2906