Abot Bpolymers in Pharmacy

8/8/2019 Abot Bpolymers in Pharmacy

1/75

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.


2/75

Pharmaceutical PolymersPharmaceutical Polymers

Definition

Compounds formed by the joining ofsmaller, usually repeating, units linked bycovalent bonds.

These compounds form largemacromolecules called as polymers.


3/75

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.


4/75

Polymers in TabletsPolymers in Tablets

Conventional (IR) Tablets where

Polymers are employed as Binders


5/75

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


6/75

Commonly used Polymers in TabletsCommonly used Polymers in Tablets


7/75

Hydrophilic Cellulose DerivativesHydrophilic Cellulose Derivatives

Hydrophilic matrices are most popular

Modified release oral dosage forms

Swellable polymers used to prolong drug

release


8/75


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


9/75


Available in several substitution and

viscosity grades

Well characterized in compendia and

most of them have US GRAS status


10/75

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


11/75



PHOTO OF SWELLEN TABLET also FIG 1


12/75



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


13/75



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


14/75



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)


15/75



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.


16/75



shows the relative positions of the three moving fronts in swellable

matrix.


17/75



The diffusion front is present as long as

the concentration of the undissolved drug

exceeds its solubility in the swollen

polymer matrix.


18/75


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.


19/75



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)


20/75



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.


21/75



Compressed matrices made of pure

polymers and drugs were assessed fortheir

swelling,

erosion, and

release properties.


22/75



Materials

HPMC 2208, 2906, 2910 (Methocel K4M,F4M, E4MCR)

HEC (Natrosol 250 M)

HPC (Klucel 99MF)


23/75



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


24/75



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


25/75


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


26/75



SWELLING AND FRONT MOVEMENTS

The position of the fronts upon water

penetration inside the tablets

The drug release behavior

Polymer dissolution


27/75




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.


28/75




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


29/75



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)


30/75




Matrix erosion is described as the

dissolution of the disentangled

macromolecules from the rubbery

polymer.


31/75




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.


32/75




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


33/75


SystemsSystems POLYMER CHARACTERISTICSPOLYMER CHARACTERISTICS -- RESULTSRESULTS

POLYMER HYDROPHILICITY

Ability to absorb water vapor In increasing order

HPC MC < HPMC 2910 HPMC 2906

Abot Bpolymers in Pharmacy

Documents

Transcript of Abot Bpolymers in Pharmacy