Drug delivery systemDrug delivery system

Controlled release systemControlled release system

AMIT M. GUPTA LECTURER, AGNIHOTRI COLLEGE OF PHARMACY, WARDHA

Sustained drug delivery systemSustained drug delivery system

• Simply prolong the drug release

• Plasma drug level for extended period of time

• Not necessarily at predetermined time rate

• Reduce dosing frequency

• Uniform plasma concentration at steady–state.

Controlled drug delivery systemControlled drug delivery system

• Prolonged release,

• Delivers the drug at predetermined rate, locally or systemically for specified period of time.

Pharmaceutical dosage forms for systemic Pharmaceutical dosage forms for systemic administrationadministration

• Generations of dosage forms– 1st gen. – conventional (unmodified) release of API– 2nd gen. – controlled release of API (CR)– 3rd gen. – targeted distribution drug delivery systems

Conventional vs. Controlled release dosage formsConventional vs. Controlled release dosage forms• I. Gen. – disintegration ( desegregation) of the dosage form and dissolution of

is spontaneous process; – drug absorption and distribution is based only on physico-chemical properties.

• II. Gen. The release is under control of the drug delivery system

– Advantages:• Avoids fluctuations of plasma drug concentration better safety and efficacy• Decreased frequency of drug administration (often once daily admin) better

compliance• May overcome some problems with BAV• Can be much more economical (better cost-effectiveness)

– Sustained release (SR) – release of the initial API dose & further prolonged release

– Controlled release (CR) – properly controlled (0. order) release

Biopharmaceutical considerationBiopharmaceutical consideration

Drug in dosage form

Drug at the absorption siteRelease

Drug in body

AbsorptionRate limiting step of controlled release

Rate limiting step of conventional release

1. Release from formulation2. Movement within body during its passage to site of action

Biopharmaceutical propertiesBiopharmaceutical properties

• Molecular weight of drug• Aqueous solubility of the drug • Apparent partition coefficient of drug• Drug pKa and pH• Drug stability in G.I.T.• Mechanism of absorption• Route of administration

Pharmacokinetic characteristics of drugPharmacokinetic characteristics of drug

• Absorption rate• Elimination half-life• Rate of metabolism• Dosage form index (DI), (plasma peak-valley

ratio i.e. Css.max to Css.min.)

Pharmacodynamic characteristics of drugPharmacodynamic characteristics of drug • Therapeutic range• Therapeutic index• Plasma concentration- Response relationship

Drug release patternsDrug release patterns

• Drug disposition fallows first order kinetics

• Rate limiting step is in the absorptions rate of drug release

• Drug release rapidly and completely absorbed

ApproachesApproaches• A. Continuous release system

1. Dissolution Controlled drug release system a. Matrix Dissolution Controlled systemb. Encapsulation/coating Dissolution Controlled drug release

system

2. Diffusion Controlled drug release system a. Matrix Diffusion systemb. Reservoir devices

3. Dissolution and diffusion Controlled drug release system

4. Ion exchange resin drug complexes5. Slow dissolving salts and complexes6. pH depending formulation7. Osmotic pressure Controlled system 8. Hydrodynamic pressure Controlled system

• Implants– Controlled drug delivery for over a long time (months/years)– Principle

• Reservoir (Osmotic/diffusion) systems• Matrix systems

– Non-biodegradable

– Biodegrable polymeric materials with dispersed drug

• Advantages – largely overcomes problems with individual compliance

• Disadvantages – mini-surgery is needed, uneasy to simply discontinue the therapy, local reactions

– Examples: hormones/contraception

Dosage forms for systemic administrationDosage forms for systemic administrationParenteral route dosage formsParenteral route dosage forms

Dosage forms for systemic administrationDosage forms for systemic administration Transdermal drug delivery sytems (TDDS)Transdermal drug delivery sytems (TDDS)

• Advantages– Elegant alternative to injectables

• Pain and stress-free• No need for trained specialist• Long-term drug delivery with minimal fluctuations of drug concentrations

– Good compliance– Unlike other controlled drug delivery systems, the delivery of the API can be

immediately discontinued (e.g., upon occurrence of adverse reactions…)

• Disadvantages– Not feasible for all API !

• Mr < 500• Well balanced lipohilicity• High potency (high doses can not be accommodated and delivered) Penetration enhancers can help!

– Local relations (irritation, disruption of barrier skin function)– Need not be practical/comfortable– Need not be cost-effective

• Examples of clinical use: hormones (HRT, contraceptives), opioid analgesics (e.g., fentanyl), nitroglycerine, nicotine (RT), clonidine or scopolamine

Delayed transit and continuous Delayed transit and continuous release system release system

1.Altered density systema. high density pellets

b. low density pellets

2.Mucoadhesive system

3.Size based system

Delayed release systemDelayed release system

1. Intestinal release system

2.Colonic release system

Parenteral Controlled release Parenteral Controlled release systemsystem

A.Injectabales1. Solutions2. Dispersions3. Microsphers and microcapsules4. Nanoparticals and niosomes5. Liposomes6. Resealed erythrocytes

B. Implants devices1. Osmotic pumps2. Vapor pressure powered pumps3. Battery power pumps

Transdermal drug delivery Transdermal drug delivery systemsystem

1. Matrix

2. Reservoir

3. Mixed Reservoir

Ophthalmic drug delivery systemOphthalmic drug delivery system

• Inserts or ocuserts

Intravaginal and intrauterine drug delivery system

Liposome's Liposome's

NiosomesNiosomes

In vitro In vitro measurements of drug availabilitymeasurements of drug availability

In vivo In vivo measurements of drug availabilitymeasurements of drug availability

Evaluation testing

Thank you Thank you

for for

your attentionyour attention