CONTROLLED RELEASEDRUG DELIVERY SYSTEMS

BY:

SURAJ CHOUDHARY

M.PHARM (PHARMACEUTICS)

DEPT. OF PHARMACEUTICS

CRDD

S

Al Ameen College of Pharmacy

PPT. PACKAGE

CONTENTS:-

2

THEME QUESTION -1THEME QUESTION -2FLASHBACKCOMPARISON - 1COMPARISON - 2MOVEMENT RESTRICTIONSCRDDS DESIGN CONSIDERATIONSPRE-REQUISITESCLASSIFICATIONCONCEPT-BASED ON CLASSESRECENT INNOVATIONS

THEME QUESTION - 1

3

4

What is DRUG DELIVERY SYSTEM?

THEME QUESTION - 2

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• Definition covers : …..

Controlled rate Localize drug action Target drug action

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What is CONTROLLED RELEASE DDS?

FLASHBACK

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HISTORY

¤ The history of controlled release technology is divided into three time periods:

1950 to 1970 - Period of SUSTAINED DRUG RELEASE

1970 to 1990 - NEEDS of the control drug delivery

1990 (post era) - MODERN ERA of controlled release technology

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COMPARISON - 1CONTROLLED RELEASE DRUG DELIVERY SYSTEMS (CRDDS)

Vs.

CONVENTIONAL DRUG DELIVERY SYSTEMS (CONVENTIONAL)

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CRDDS VS CONVENTIONAL

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• Conventional

Periodic administration

Non-specific administration

High systemic concentrations can be toxic, causing side effects or damage to organs.

Low concentrations can be ineffective.

• CRDDS

Drug Concentration rises quickly to effective level.

Effective concentration is maintained for extended time.

11CRDDS VS CONVENTIONAL

• Conventional

Inconvenient

Difficult to monitor

Careful calculation necessary to prevent overdosing

Large amounts of drug can be “lost” when they don’t

get to the target organ

Drug goes to non-target cells and can cause damage

Expensive (using more drug than necessary)

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DISADVANTAGES OF CONVENTIONAL

COMPARISON - 2CONTROLLED RELEASE DRUG DELIVERY SYSTEMS (CRDDS)

Vs.

SUSTAINED RELEASE DRUG DELIVERY SYSTEMS (SR)

13

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CRDDS VS SR

• Sustained Release

Controlled drug delivery

Well - characterized and

reproducible dosage form

Controls entry to the body

according to the specifications

of the required drug delivery

profile.

(rate and duration of delivery

are designed to achieve

desired concentration)

• CRDDS

Release of drug is

extended in time

Rate and duration are

not designed to

achieve a particular

profile.

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CRDDS VS SR

MOVEMENT RESTRICTIONS

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Cost of formulation

Fate of CRDDS Biocompatibility Fate of

polymer,etc.

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CHALLENGES IN CRDDS

Drug absorption, distribution and metabolism vary

among individuals

Individualized therapy

Controlled release

CRDDSDESIGN CONSIDERATIONS

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Route of delivery Target sites

1. Desired site for efficacy

2. Sites to avoid to minimize side effects Type of therapy

1. Acute or chronic – rate and duration

e.g., 1 yr duration implant vs. antibiotic for acute infection Patient condition

1. Cognitive ability and memory

2. Physical condition – ambulatory, bedridden, etc.

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DESIGN CONSIDERATIONS

Polymer design considerations

1. Physical properties Glass transition

temperature Diffusion

characteristics

2. Compatibility with active

3. Stability – must not decompose in storage

4. Biocompatibility of polymer and degradation products

5. Ease of formulation and fabrication

6. Mechanical properties are stable when drug is added

7. Cost

Agent

1.Physicochemical properties

2.Stability

3.Solubility

4.Partitioning

5.Charge

6.Protein binding properties

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DESIGN CONSIDERATIONS

PRE-REQUISITES

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PRE-REQUISITES ……OF A RESPONSIVE DRUG DELIVERY SYSTEM

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• Controlled release profiles, especially for sensitive drugs

• Long-lived, Biocompatible and inexpensive

• Safe from accidental release, easy to fabricate and sterilize and allow high drug loading

• Inert, mechanically strong, easy to implant and remove (patient compliance)

• Continuous monitoring, telemetric data transfer and allow physician intervention if needed

BASIC MECHANISMS

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MECHANISMS24

PARTITION

DISSOLUTION

DIFFUSION

OSMOSIS

EROSION

SWELLING TARGETTING

COMBINATION

CLASSIFICATION

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Based on the……………

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CLASSIFICATION CRITERIA

TECHNICAL SOPHISTICATION

ROUTES OF DELIVERY

27BASED ON THE

TECHNICAL SOPHISTICATION

Rate-Preprogramm

ed DDS

Activation-Modulated

DDS

Feedback-Regulated

DDS

Site-Targeting DDS

Rate of release of the drug has been PRE-PROGRAMMED at specific rate profiles.

Fick’s law of diffusion are often followed.

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RATE-PREPROGRAMMEDDRUG DELIVERY SYSTEMS

Drug Reservoir

Rate-Controlling surface

Drug

1. Polymer Membrane Permeation

Ex: i. Norplant subdermal implant (levonorgestrol, encap/sd)

ii. Occusert system (Pilocarpine – Ethylene acetate mem)

iii. Transderm-Nitro (disp. Of Nitroglycerine-lactose triturate)

2. Polymer Matrix Diffusion Controlled

Ex: i. Nitro-Dur (Nitroglycerin)

ii. Compudose subdermal implant (Estradiol)

3. Polymer Micro-reservoir Partition

Ex: i. Nitrodisc (Nitroglycerin)

ii. Subdermal Synvro-Mate-C implant (Norgestomet-PEG 400)

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RATE-PREPROGRAMMEDDRUG DELIVERY SYSTEMS

Rate of release of the drug has been ACTIVATED by some physical, chemical or Bio-chemical processes.

Or it may be activated even by the energy supplied externally.

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ACTIVATION-MODULATEDDRUG DELIVERY SYSTEMS

Drug Reservoir

Rate-Controlling surface

Drug

Energy Sensor

1. Physical Means Osmotic pressure activated

Ex: Acutrim Tab (PPA HCl)

Hydrodynamic pressure activated

Vapor pressure activated

Ex: Infusaid pump (Heparin)

Mechanically activated

Ex: M.D.Nebulizer (Buserelin)

Magnetically activated

Ex: Hemisphere (Bovine serum albumin)

Sonophoresis activated Iontophoresis

activatedEx: Phoresor by Motion Control (for anti-inflammatory drugs)

Hydration activatedEx: Valrelease Tab (Valium)

2. Chemical Means pH-activated Ion-activated Hydrolysis-

activated

3. Biochemical Means

Enzyme-activated

Ex: Albumin microspheres (5-Fluorosil)

Biochemical-activated

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ACTIVATION-MODULATEDDRUG DELIVERY SYSTEMS

Rate of release of the drug has been activated by a

triggering agent, such as biochemical substance (in the

body) & also regulated by it’s concentration via some

FEEDBACK mechanisms.

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FEEDBACK-REGULATEDDRUG DELIVERY SYSTEMS

Drug Reservoir

Rate-Controlling surface

Drug

Biochemical responsive/Energy

Sensor

1. Bioerosion regulated

Ex: Urea activated Hydrocortisone

2. Bioresponsive

Ex: Glucose triggered Insulin

3. Self-regulating

Ex: Glycosylated Insulin-

Concanavalin A

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FEEDBACK-REGULATEDDRUG DELIVERY SYSTEMS

Proposed by Ringsdorf. Consists of following parts attached to the non-immunogenic & biodegradable polymer:

1. Site-specific targeting moiety 3. Drug moiety with spacer

2. Solubilizer

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SITE TARGETTINGDRUG DELIVERY SYSTEMS

Drug ReservoirRate-Controlling

surface

Drug

Biochemical responsive/Energy

Sensor

Site-TargettingMoiety

35BASED ON THE

ROUTE OF ADMINISTRATION

Oral DDS

Mucosal DDS

Nasal DDS

Ocular DDS

Transdermal DDS

Parenteral DDS

Vaginal DDS

Intrauterine DDS

• Osmotic Pressure

• Hydrodynamic Pressure

• Membrane Permeation Microporous MP Gastric Fluid-Resistant Intestine-Targeted

• Gel Diffusion

• pH

• Ion-Exchange

36BASED ON THE

ORAL DRUG DELIVERY

• Nasal delivery of…………..

- Organic based Pharmaceuticals

- Peptide based Pharmaceuticals

• Development of……………

- Epinephrine-Releasing

- Hydrophilic Contact lenses

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NASAL DRUG DELIVERY

OCULAR DRUG DELIVERYNON-INVASIVE

• Transdermal delivery of…………..

- Polymer Membrane Permeation

- Polymer Matrix Diffusion

- Drug Reservoir Gradient

- Micro reservoir Dissolution

• Development of……………

- Dissolution-Controlled Depot

- Adsorption-type Depot

- Encapsulation-type Depot

- Esterification-type Depot

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TRANSDERMAL DRUG DELIVERY

PARENTAL DRUG DELIVERY

RECENT TRENDS39

REFERENCES

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1. Chien Y W; Novel Drug Delivery Systems; Informa

Healthcare, 2nd Edition, 2009.

2. Siegel R A and Rathbone M J; Overview of

Controlled Release Mechanisms; Advances in

Delivery Science and Technology, 2012.

3. Bhowmik D, et.al; Recent trends in scope and

opportunities of control release oral drug

delivery systems; Critical review in pharmaceutical

sciences, (1): 2012.

4. Ummadi S, Shravani B; Overview on Controlled

Release Dosage Form; International Journal of

Pharma Sciences, 3(4); 2013.

Thank you all…...For your Attention!!!!!