SEMINARON

PULSATILE DRUG DELIVERY SYSTEMS

Presented by:CHIRANJIBI ADHIKARI

I M. Pharm (Pharmaceutics)Mallige college of pharmacy

CONTENTS

Introduction

Necessity of Pulsatile Drug Delivery

Advantages

Limitations

Methods for Pulsatile Drug Delivery

Introduction:

Pulsatile drug delivery systems are developed to deliver drug according to

circadian behavior of diseases. This means that these systems will deliver

drug at time when disease displays its most morbid and mortal state within a

circadian cycle (24 hrs.).

The product follow a sigmoidal drug release profile characterized by a time

period of no release (lag time) followed by a rapid and complete drug

release. Thus drug can be delivered at right time, in right amount and at right

site of action by use of such approach.

Fig. Drug release profiles from pulsatile drug delivery system

where, A: Conventional release profile,

B: Burst release of drug after a lag time,

C: Delayed release profile after a lag time,

D: Constant release profile in prolonged period after a lag time,

E: Extended release profile without lag time

The principle basis for the use of pulsatile release is for the drugs where a constant drug release, i.e., a zero-order release is not desired.

Recent studies have revealed that diseases have predictable cyclic rhythms and that the timing of medication regimens can improve outcome in selected chronic conditions.

The potential benefits of chronotherapeutics have been investigated and established for number of diseases like asthma, arthritis, cancer, diabetes, epilepsy, hypertension, ulcer, hypercholesterolemia etc.

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Fig. Schematic diagram of circadian rhythm showing diseases require PDDS.

Diseases required pulsatile delivery

Chronological behavior Drugs used Diseases

1. Acid secretion is high in the H2 blockers Peptic ulcerafternoon and at night

2. Precipitation of attacks during β2 agonist, Asthmanight or at early morning Antihistamines

3. BP is at its lowest during the Nitroglycerin, Cardiovascularsleep cycle and rises steeply calcium channel blocker, during the early morning ACE inhibitors

4. Pain in the morning and more NSAIDs, Arthritispain at night Glucocorticoids

5. Increase in the blood sugar Sulfonylurea, Diabetes mellitus level after meal Insulin

6. Cholesterol synthesis is HMG CoA Hyperchole-generally higher during night reductase inhibitors sterolemiathan day time

NECESSITIES OF PULSATILE DDS

1. First pass metabolism:

3. Special chronopharmacological needs:

2. Biological tolerance:

4. Local therapeutic need:

5. Gastric irritation or drug instability in gastric fluid:

Transdermal nitroglycerin, salbutamol sulphate.

Beta blockers and salicylamide.

Asthma and angina pectoris attacks are most frequently in the morning.

Inflammatory bowel disease.

Protection from gastric environment is essential for the drugs that undergo degradation in gastric acidic medium (e.g.-peptide drugs),irritate the gastric mucosa(NSAIDS) or induce nausea and vomiting.

ADVANTAGES OF PULSATILE DRUG DELIVERY SYSTEM

i. Increases absorption and bioavailability than conventional

immediate release or sustained release drug.

ii. Site targeting allows delivery of poorly bioavailable drugs that

would get destroyed in GI tract environment.

e.g., peptide and protein molecules.

iii. Reduces dose of drug without decrease in therapeutic effects.

iv. No risk of dose dumping and side effects.

v. Less inter- and intra-subject variability.

v. Pulse release allows multiple dosing in a single dosage form.

vi. The system can be utilized for many solid dosage forms like

granules, microspheres, microparticles, tablets, capsules, and

pellets.

vii. Limited risk of local irritation.

viii. Improve stability.

LIMITATIONS OF PDDS:

i. Multiple manufacturing steps and large number of process variables.

ii. Homogeneity of the coated barrier is mandatory to assure the

predictability of the lag time.

iii. Rupture time cannot be always adequately manipulated as it depends on

the physicochemical properties of the polymer.

iv. Higher cost of production.

v. Raw material is not easily available.

v. Dosage form design requires highly skilled/ trained professionals.

vi. Technologies employed and the equipments used are complicated.

METHODS OF PULSATILE DDS

I. Single unit (e.g., tablet or capsule) systems

II. Multiple unit (e.g., pellets, beads) systems.

I. Single-unit systems

Capsular Systems

Pulsatile delivery by Osmosis

Pulsatile system with erodible or Soluble barrier coating

Pulsatile system with Rupturable coating

1. Capsular SystemsDesign of Pulsincap® system

2. Pulsatile delivery by OsmosisPort® System

3. Pulsatile system with erodible or

Soluble barrier coating

4. Pulsatile system with Rupturable coating

II. Multiple-unit systems

Pulsatile delivery systemby change in membrane permeability

Pulsatile System Based on Rupturable Coating

Osmotic-Based Rupturable Coating Systems

Marketed technologies of pulsatile drug delivery

Technology Mechanism API Disease

OROS* Osmotic mechanism Verapamil HCL Hypertension

Three dimentional Externally regulated Diclofenac Inflammationprinting* system sodium

PulsincapTM Rupturable system Dofetilide Hypertension

Pulsatile system gaining a lot of interest as it is increasing patient compliance by means of providing time- and site specific drug delivery system.

PDDS can provide increased therapeutic benefits to the patients,

holds good promises of benefit to the patients suffering from chronic

problems like arthritis, asthma, hypertension etc.

The potential therapeutic benefits of pulsatile drug delivery systems

should ensure that the current high level of interest in this area would

stretch well into future and ensures the betterment of quality life.

Conclusion:

Thank you