application of polymers in oral sustained drug delivery system

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APPLICATIONS OF POLYMERS IN ORAL SUSTAINED DRUG DELIVERY SYSTEM

Prepared By-Mr.Bhamare Prashant Jayawant

M.Pharm, Sem I

DEPARTMENT OF PHARMACEUTICSR.C.Patel Institute of Pharmaceutical Education and Research,Shirpur.

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Content

• Definition of Polymer

• Definition of Sustained drug delivery system

• Advantages and disadvantages of SRDDS

• Criteria for SRDDS

• Polymer used in Formulation approaches of SRDDS

• Formulation Approaches of SRDDS

• Example of matrix tablet

• Conclusion

• References

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Definition of polymer

Polymer is a high molecular weight compound containing covalently bonded repeated units of monomers.

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ORAL SUSTAINED DRUG DELIVERY SYSTEM

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Sustained drug delivery system

“Drug Delivery systems that are designed to achieve prolonged therapeutic effect by continuously releasing medication over an extended period of time after administration of single dose.”

To achieve steady state blood level that is therapeutically effective and non toxic for an extended period of time.

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Comparison of drug release profile

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Advantages of SRDDS

• Decreased local and systemic side effects reduced

gastrointestinal irritation.

• Reduction in dosing frequency.

• Improved patient compliance and reduced patient care time.

• Reduced fluctuations in circulating drug levels

• Reduced cost.

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Disadvantages of SRDDS

• Unpredictable or poor in-vitro and in-vivo correlation.

• Dose dumping.

• Dose adjustment is difficult.

• More costly process and equipment are involved in

manufacturing many sustained release dosage forms. 

• Cost of single unit higher than conventional dosage forms.

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Criteria for SRDDS

In general the drugs best suited for SRDF having following characteristics-

• It should be effectively absorbed by oral route and stable in GI fluid.• Dug that have short half- life (2-4 hrs) and elimination half-

life is 8 hrs.• Desirable absorption and solubility characteristics• Are administered in relatively small doses (0.5-1gm)• Possess a high therapeutic index• Are used in the treatment of chronic rather than acute

conditions.

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Classification of polymers used in sustained release drug delivery system according to their characterctics

Sr no. Polymer Characteristics

Material

1. Insoluble, Inert polymer Polyethylene, polyvinyl chloride, ethyl cellulose.

2. Insoluble, Erodible polymer

Stearyl alcohol, stearic acid, polyethylene glycol, castor wax, polyethylene glycol monostearate.

3. Hydrophilic Polymer Methyl cellulose, Hydroxyethyl cellulose, HPMC, Sodium CMC, Carboxypolymethylene.

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Formulation approaches of SRDDS

1. Dissolution controlled system a) Matrix system b) Reservoir system 2. Diffusion controlled system a) Matrix system b) Reservoir system 3. Method using Ion exchange resin 4. Method using osmotic pressure 5. pH independent formulation 6. Altered density formulation

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MECHANISM OF RELEASE OF DOSAGE FROM SRDF

Dissolution Controlled System

Matrix system

Reservoir system

Diffusion Controlled System

Matrix system

Reservoir system

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1.Dissolution controlled system

• A drug with a slow dissolution rate is inherently sustained and for those drug with higher water solubility, one can decrease dissolution trough specific polymer is used.

• These systems are most commonly employed in the production of enteric coated dosage forms. The rate of dissolution is given by following equation

Where, S= aq. Solubility of drug A= surface area of tablet D= Diffusivity of drug H= thickness of boundary layer

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Dissolution controlled system

1.Matrix System-• It consists of a drug mixed with a polymer which will be subjected

to slow erosion of the matrix in the GIT. e.g. Waxes 2. Reservoir System-• In this system drug is coated with a given thickness coating of

polymer which is slowly dissolved in the content of GIT by alternating layer of drug with the rate controlling coats.

e.g. Cellulose and cellulose derivative Polyethylene glycol

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Polymer used in Dissolution controlled system

• Slowly soluble and erodible materials:- 1.PVP with cellulose 2.PMA 3.Waxes- Bees wax, micro crystalline wax, carnauba wax. 4.Cellulose- MC, HEC, HPMC. 5.Polyethylene glycol

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2.Diffusion controlled system• Diffusion process shows the movement of drug molecules from a

region of a higher concentration to one of lower concentration.• This DDS can be prepared either by encapsulating the drug in

polymer or dispersing the drug in the matrix. The rate of diffusion is given by following equation

Where, K= Partition co-efficient of drug between drug core and membrane A = surface area of tablet D = Diffusion co efficient l = Diffusion path length ▲C = Concentration difference across membrane

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1)Matrix controlled system• The matrix system in which one or more drug mixed with

gelling agent i.e. hydrophilic polymers.• It is the release system which prolongs and controls the release

of drug that is dissolved or dispersed.

Types of diffusion matrix system- 1. Hydrophobic matrix system 2. Hydrophilic matrix system 3. Fat-wax matrix system

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Polymer used in matrix system

1. Hydrophilic polymer- e.g. HPMC, HPC, HEC, xanthan gum, sodium alginate, copolymer of acrylic acid. 2. Hydrophobic polymer- e.g. Waxes and water insoluble polymer. 3. Waxes- e.g. Carnauba wax, bees wax, microcrystalline wax, paraffin waxes, ozokerite wax.

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Example of matrix tablets

DRUG BRAND NAME

ACTION DOSE POLYMER USED IN DRUG

Zidovudine Retrovir Extended release

300 mg 200 mg

Carbopol, HPMC, EC.

Diclofenac sodium

Voltaren Extended release

100 mg Sod. CMC, Sod. Alginate, chitosan, EC.

Metformin HCL

Glumetza Sustained release

500 mg HPMC K15 M, K 10, EudragitRL100 &RS100

Aceclofenac

Aceclofan Extended release

250mg HPMC K100 M, K15 M

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2)Reservoir controlled system• In this system, a water insoluble polymeric material covers a

core of drug. Drug will partition into the membrane and exchange with the fluid surrounding the particle or tablet.

• Additional drug will enter the polymer, diffuse to the periphery and exchange with the surrounding media. e.g. Ethyl cellulose, PMA, HPC, Polyvinyl acetate.• Example of reservoir tablet- Morphine sulfate (kadian) - HPMC, EC, PEG, methacrylic acid. Dose – 20 mg-100 mg capsules.

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Conclusion

• The dosage provide increased bioavailability of the drug,

reduction in the frequency of administration of drug and

improves the specific distribution of the drug.

• The various polymer used in SDDS formulation for the

therapeutic effect of the drug is release extended period of

time.

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References 1. Polymer science by V.R.Gowariker, N.V.Viswanthan, Jayadev Sreedhar, New age international ltd. Publishers, Page no- 9-14. 3. Modern Pharmaceutics by Gilbert S. Banker, Christopher T. Rodes, Fourth edition, Revised and expanded, Page no-501-511. 4. A review article on novel oral sustained release technology by International journal of research and development in pharmacy and life science, page no- 262-265. 4. Sustained drug delivery system by Indian journal of research in and biotechnology, page no- 305-310. 5. An overview: Oral sustained release drug delivery system, page no- 57-62. 6. A review article on Sustained release oral drug delivery system by International journal of pharma research & review , page no-11-21.

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