This seminar discusses pulsatile drug delivery systems, which deliver drugs according to circadian rhythms to time their release when diseases are most active. Such systems provide a lag time followed by a rapid and complete drug release. This allows drugs to be delivered at the right time, amount, and site of action. Pulsatile delivery provides benefits like increased absorption, site targeting of drugs, reduced dosing, and less side effects. Various methods were presented including single and multiple unit systems using coatings that erode, rupture or allow osmotic pumping at the desired time. Marketed technologies like OROS and Pulsincap were highlighted. Pulsatile delivery holds promise for improving treatment of chronic diseases like asthma, arthritis and

1. SEMINAR
ON
PULSATILE DRUG DELIVERY SYSTEMS
Presented by:
CHIRANJIBI ADHIKARI
I M. Pharm (Pharmaceutics)
Mallige college of pharmacy

2. CONTENTS
Introduction
Necessity of Pulsatile Drug Delivery
Advantages
Limitations
Methods for Pulsatile Drug Delivery

3. 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.

4. 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

5. 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.

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

7. Diseases required pulsatile delivery
Chronological behavior Drugs used Diseases
1. Acid secretion is high in the H2 blockers Peptic ulcer
afternoon and at night
2. Precipitation of attacks during β2 agonist, Asthma
night or at early morning Antihistamines
3. BP is at its lowest during the Nitroglycerin, Cardiovascular
sleep cycle and rises steeply calcium channel blocker,
during the early morning ACE inhibitors
4. Pain in the morning and more NSAIDs, Arthritis
pain 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 sterolemia
than day time

8. 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.

9. 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.

10. 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.

11. 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.

12. 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

13. 1. Capsular Systems
Design of Pulsincap® system

14. 2. Pulsatile delivery by Osmosis
Port® System

16. 3. Pulsatile system with erodible or
Soluble barrier coating

17. 4. Pulsatile system with Rupturable coating

18. II. Multiple-unit systems
 Pulsatile delivery systemby change in membrane permeability
 Pulsatile System Based on Rupturable Coating
 Osmotic-Based Rupturable Coating Systems

19. Marketed technologies of pulsatile drug delivery
Technology Mechanism API Disease
OROS* Osmotic mechanism Verapamil HCL Hypertension
Three dimentional Externally regulated Diclofenac Inflammation
printing* system sodium
PulsincapTM Rupturable system Dofetilide Hypertension

20. 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:

21. Thank you