1. Sustained release dosage
forms
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2. •
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Introduction-definition
Concept
Objectives
Advantages and disadvantages
Dose considerations
Formulation
Types of SR systems
Diffusion systems
Dissolution systems
Ion exchange sys
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3. • Oral SR delivery systems
design and types
• Parentral SR dosage forms
types and routes
• References
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4. IDEAL DRUG DELIVERY SYSTEM
• should deliver drug at a rate dictated by the needs of the
body over the period of the treatment.
• should channel the active entity solely to the site of action.
• This is achieved by development of new various modified
drug release dosage forms, like-
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Control release dosage forms
Time release dosage forms
Sustained release dosage forms
Site specific or targeted drug delivery systems etc.
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5. “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.”
Basic goal of the therapy
to achieve steady state blood level that is
therapeutically effective
& non toxic for an
extended period of time.
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6. Sustained release drug
profile
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7. Objectives of drug delivery
• Temporal drug delivery:
controlling the rate or specific time
of drug delivery to the target tissue.
• Spatial drug delivery:
targeting a drug to a specific organ
or tissue.
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8. advantages
Reduction in fluctuation in steady state levels
Increased safety of high potency drugs
Total amount of dose is decreased
Improved patient compliance
disadvantages
Poor in vivo-in vitro correlation
Possibility of dose dumping
Retrieval of drug is difficult
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Dose adjustments is difficult
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9. • Biopharmaceutical properties:
Molecular size
Aqueous solubility
Partition coefficient
Dissociation constant
less than 600 Daltons
more than 0.1 mg/ml
between 1 to 2
pka acidic drugs pka>2.5
Basic drugs pka<11
Absorption mechanism
passive but not through
Window
Ionisation at physiological pH NMT 95%
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10. Pharmacokinetic properties
• Absorption rate constant ka high(btw 0.170.23/hr)
• Elimination half life t1/2
2-6 hrs
• Metabolism rate
not too high
• Dosage form index(ratio of cssmax /css min)
One
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11. Pharmacodyanamic properties
Dose
max 1.0g
(in a controlled release form)
Therapeutic range wide
Therapeutic index wide
 PK/PD relationship good
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12. • Divided into two considerations
1.Release rate consideration
Release rate consideration :-
In conventional dosage form Kr>Ka - release of
drug from dosage form is not rate limiting step.
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13. (Kr>>Ka) in immediate release
non immediate (Kr<<<Ka) i.e. release is rate
limiting step.
The release should follow zero order kinetics
(clinically equivalent to constant release in many
cases)
Kr = rate in = rate out = Ke.Vd.Cp
Ke = Elimination rate constant (first order
kinetics).
Vd = Total volume of distribution.
Cp = Plasma drug concentration.
Kr = zero order release rate constant
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14. b)Dose consideration:
for zero order release
core
Maintenance dose
Immediate release
component
a) Initial (primary) dose Di
b)Maintenance dose
Dm = kr .Td
Td=total time required for extended release dosage form
therefore, total dose W
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W= Di + Dm
W=Di +Kr.Td
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15. If maintenance dose begins to release the drug
during dosing t=0 then,
W = Di + K r. Td – Kr.Tp
Tp = time of peak drug level.
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16. First order release
rate in=rate out
Dm.kr=ke.Cp.Vd
Dm=ke.Cp.Vd/kr
W=Di+Dm
W=Di+(keCp/kr)Vd
kr= first order release rate constant
ke=elimination rate constant
Cp=plasma drug concentration
If drug begins to release maintenance dose at T=0
W=Di+(keCp/kr)Vd - DmkeTp
Tp= time of peak plasma drug concentration
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17. Diffusion systems
• Porous matrix controlled system
Rate controlling element-water swellable material e.g.
xanthan gums ,guar gum , high viscosity grades of
HPMC,HPC, alginates or non- swellable water insoluble
polymers such as ethylcellulose
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18. • Porous membrane controlled system
rate controlling element – non-swellable
water insoluble polymer e.g. ethylcellulose,
PMA. Drug release controlled through
micropores.
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19. • Can be in following ways:Slow dissolution of drug
1. Drug with inherently slow dissolution rate.
2. Drugs that transforms into a slow dissolving form.
Slow dissolution rate of reservoir memb. &
matrix
1. Embedment in slowly dissolving, degrading erodible matrix.
2. Encapsulation or coating with slowly dissolving degrading erodible
subs.
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20. • slowly soluble and erodible materials:Ethylcellulose,
PVP with cellulose
PMA(eudragits),
Waxes(glyceryl monostearate)
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21. Erosion controlled
Polymer or wax degradation brought about by:
enzyme,
pH change
osmotic pressure
• Bulk erosion(A)
homogeneous erosion
• Surface erosion(B)
heterogenous erosion
when water penetration is restricted to surface
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22. ORAL SUSTAINED RELEASE
DESIGN
• Continuous release systems-release drug
continuosly over extended period of time.
• Pulsatile release systems:characterize by a lag time then rapid &
complete /extended release.
Advantages:1. Drugs with extended first pass e.g. Propranolol
2. Targeting e.g. in intestinal inflammations
3. Protection of gastric or upper intestinal mucosa from
irritating drugs.
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23. Following methods can be used to prepare
sustained release oral preparation:• Increasing the particle size of the drug
• Embedding the drug in a polymeric matrix.
• Coating the drug or dosage form containing
drug(microencapsulation).
• Forming complexes of the drug with material such
as ion exchange resins.
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24. 1)Increasing the particle size of the drug
• Increasing particle size decreases the surface
to volume ratio slow the rate of drug availability.
•This method is limited to poorly soluble drug .
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25. 2) Embedding the drug in matrix
• Matrix is a uniform dispersion of drug with polymer
matrix
• Continuous external phase of the dispersion effectively
impede the passage of the drug from the matrix.
• Drug release through-diffusion
• Least complicated approaches to manufacture sustained
release dosage form involves the direct compression of
drug, materials & additives to form a tablet .
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26. polymers
•Insoluble, inert - polyethylene, polyvinyl
chloride, methyl acrylate, ethylcellulose.
•Insoluble, erodible – carnauba wax, stearyl
alcohol, castor wax.
•Hydrophilic – methyl cellulose, hydroxyl ethyl
cellulose, sodium carboxymethyl cellulose,
sodium alginate.
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27. 3) Microencapsulation
• method for retarding drug release by coating its
surface with a material(polymers) that retards
penetration by the dispersion fluid.
• it is a means of applying relatively thin coating
to small particles of solid or droplets of liquids and
dispersion.
Can be done byspray congealing
spray drying
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28. Polymers:
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Polyvinyl alcohol
Polyacrylic acid
Ethyl cellulose(pH sensitive)
Polyethylene
Polymethacrylate
Poly (ethylene-vinyl acetate)
Cellulose nitrite
Silicones
Poly (lactide-co-glycolide)
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29. 3)Ion exchange resins
• Sustained delivery of ionizing acidic & basic drug
can be obtained by complexing them with insoluble
non-toxic anion exchanger & cation exchanger resin
respectively.
• Release by diffusion .
• The complex can be prepared by incubating the
drug-resin solution or passing the drug solution
through a column containing ion exchange resin.
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30. Advantages
• Resinates prevent dose dumping
• Uniform release of drug
• Flexibity in designing various dosage forms
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31. Types of resinates
• Simple resinates
• Microencapsulated or coated resinates-rate
controlling membrane of polymers(EC,waxes etc)
polymer
Drug+resin
polymer
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32. • Pennkinetic systems
drug resinate is pre treated with PEG 400
Coated with water insoluble polymer
PEG-controls rate of swelling of resinate mixture in water.
EC-modifies diffusion pattern of ions in & out.
• Hollow fibre systems-resinates filled into
hollow fibres of suitable polymeric materials
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33. ADVANTAGES
• Convenience and ease of administration
• Flexibility in DFD
• Ease of production.
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35. INJECTABLES
SOLUTIONS
Both aqueous & oily
aqueous solution
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High viscosity solutions
For cmpds more than ml wt 750
For water soluble drugs
Gelling agents & viscosity enhancers are used
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36. drug release is controlled by:• By increasing viscosity of vehicle by mc,cmc
pvp
• Forming a complex with macromolecules
• Forming complex & decreasing solubility of
drug
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37. Oil solutions
• Release drug by partioning the drug between
oil &aqueous body fluid.
• Vegetable oils like-arachis oil,cottonseed
oil
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38. • Emulsions- o/w,
adm of liquid oily drugs
(i.v, s.c,i.m)
• Suspensions-solid particles in aqueous vehicle
solid content 0.5%-5.0%, size <10μ
(s.c,i.m)
for drugs insoluble in water
• Microspheres-polymeric particles,
site specific delivery
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39. • Liposomes- liquid based vesicles
diameter range 25nm-10000nm
phospholipids
i.v,s.c,i.m,intra-CSF
• Nanoparticles-polymeric liquid particles
biodegradable polymers
i.v,s.c, i.m
• Niosomes-
surfactant vesicles
non-ionic surfactant
i.v,i.m,s.c
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40. Drug loading-immersing in buffered hypotonic
solution
Resealing-restoring isotonicity & incubation at
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Target organs-liver &spleen
• Advantages
biodegradable & non-immunogenic
carry large doses
targeted drug delivery
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41. • Leon lachman – The theory and practic of
industrial pharmacy
• D.M. Brahmankar and Sunil B. Jaiswal, Biopharmaceutics
and Pharmacokinetics: A Treatise. 1995, 1st Edn, Published by
M. K. Jain for Vallabh Prakashan
• .Remington, The science and practice of
pharmacy, 21st Edition.
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