This document discusses pulsatile drug delivery systems (PDDS), which aim to release drugs in a programmed pattern that corresponds to circadian rhythms or specific disease states. It outlines the objectives and methodology. Key points include: PDDS are advantageous over sustained release for diseases with circadian rhythms; examples are hypercholesterolemia, asthma, diabetes, and cardiovascular diseases. The document classifies and describes different types of PDDS, including internal stimuli-induced, temperature-induced, pH-sensitive, glucose-responsive, time-controlled, inflammation-induced, and externally regulated systems. In conclusion, PDDS can effectively deliver drugs according to the body's circadian clock.
4. PULSATILE DRUG DELIVERY
SYSTEM(PDDS)
It is defined as the rapid and transient release of a
certain amount of drug molecules within a short time-
period immediately after a predetermined off-release
period i.e. lag time
It aims to release drug on programmed pattern
PDDS are advantageous over sustained release drugs
because many of diseased condition follow some
circadian rhythm
For which maintaining the drug plasma level is not a
5.
6. Disease Demanding The
PDDS
Hypercholesterolemia
circadian rhythm occurs during hepatic
cholesterol synthesis
cholesterol synthesis is generally higher during
the night than during daylight
maximal production occurs early in the morning,
i.e. 12 h after the last meal
Studies suggests evening dosing to be effective
than morning
7. Asthma
airway resistance increases progressively at night in
asthmatic patients
Duodenal ulcer
gastric acid secretion is highest at night , while
gastric and small bowel motility and gastric emptying
are all slower at night
peptic ulcer patients, gastric acid secretion is highest
during the night
Thus bedtime dosage is much effective
8. Diabetes
Insulin level varies with time
It is highest after meal
Thus PDDS is of demand which release the in
response to the plasma insulin concentration
Cardiovascular diseases
Blood pressure (BP), heart rate, stroke volume,
cardiac output, blood flow of the cardiovascular
system are subject to circadian rhythms
BP is at its lowest during the sleeping period and
rises steeply during the early morning period
9. capillary resistance and vascular reactivity are
higher in the morning and decrease later in the
day
Thus Demands a PDDS
10.
11.
12. NECESSITIES OF PDDS
First pass metabolism
Biological tolerance
Special chronopharmacological needs
Local therapeutic need
Gastric irritation or drug instability in GI tract
13. Classification of PDDS
PDDS
Internal stimuli
induced
system
Temperature
induced
PH sensitive
Inflammation
induced
Glucose
responsive
Time
Controlled
Externally
regulated
14. Internal Stimuli Induced
System
drug release takes place after stimulation by
any biological factor like temperature, or any
other chemical stimuli
Chemical Stimuli
1. Enzymes
2. Hormones
3. pH
15. Temperature Induced Drug
Release
Deviation of temperature acts as stimulus and
triggers drug release
Useful for disease accompanying fever
16. pH Sensitive Drug Release
polyelectrolytes that bear weak acidic or basic
groups that either accept or release protons in
response to changes in environmental pH are
used for drug release
Polyeectrolytes are cellulose acetate
phthalate, polyacrylates, sodium carboxy
methyl cellulose.
17. Glucose Responsive
Increased concentration of either Glucose
oxidase or Gluconic acid lowers the pH to
approx 5.8
pHsensitive hydrogels for modulated insulin
delivery
GLUCOS
E
Gluconic
acid
Glucos
e
Oxidas
e
18. pHsensitive hydrogels for modulated insulin
delivery
pH change induces swelling of the polymer which
results in insulin release.
Insulin reduces blood glucose level
gluconic acid level also gets decreased and
system turns to the deswelling mode thereby
decreasing the insulin release.
19. Inflammation Induced
Physical or chemical stress, such as injury,
broken bones, etc., initiates inflammation
reactions, because of which hydroxylradicals
('OH) are produced from these inflammation-
responsive cells.
Hyalauric acid(HA) was used for the
inflammation induced delivery system.
20. HA is mainly degraded either by hydroxyl
radicals or a specific enzyme, hyaluronidase
Degradation by Hydroxyl radical is more
prominent
Thus, it is possible to treat patients with
inflammatory diseases like rheumatoid
arthritis; using anti-inflammatory drug
incorporated in HA gels as new implantable
drug delivery systems
21. Time Controlled
Rupture Of Coating
these systems are dependent on the
disintegration of the coating for the release of
drug
Pressure for the rupture of the coating is achieved
by the swelling, disintegrants or osmotic pressure
Erosion or Solubilization of Layer
the core containing drug is coated with the soluble
or erodible polymer as outer coat and drug
release is controlled by the dissolution or erosion
of the outer coat
24. Externally Regulated
Magnetic induces release
Ultrasound induces release
Electric field induces release
Light induces release
25. Conclusion
PDDS is useful in disease following biological
rhythm
In Circadian disorders such as hypertension,
osteoarthritis, asthma etc., which require
chronopharmacotherapy
PDDS can effectively tackle this problem as it
is modulated according to body's circadian
clock giving release of drug after a specified
time lag
Various pulsatile technologies are researched
and some are currently in the market.
when gastric motility and emptying are slower, drug disintegration, dissolution, and absorption may be slower
1. First pass metabolism
Some drugs, such as beta blockers, and
salicylamide, undergo extensive first pass
metabolism and require fast drug input to
saturatemetabolizing enzymes in order to minimize
pre-systemic metabolism. Thus, a
constant/sustained oral method of delivery would
result in reduced oral bioavailability.
2. Biological tolerance
Continuous release drug plasma profiles are often
accompanied by a decline in the
pharmacotherapeutic effect of the drug, e.g.,
biological tolerance of transdermal nitroglycerin.
3. Special chronopharmacological needs
Circadian rhythms in certain physiological
functions are well established. It has been
recognized that many symptoms and onset of
disease occur during specific time periods of the 24
hour day, e.g., asthma and angina pectoris attacks
are most frequently in the morning hours.
4. Local therapeutic need
For the treatment of local disorders such as
inflammatory bowel disease, the delivery of
compounds to the site of inflammation with no loss due to absorption in the small intestine is highly
desirable to achieve the therapeutic effect and to
minimize side effects.
5. Gastric irritation or drug instability in
gastric fluid
For compounds with gastric irritation or chemical
instability in gastric fluid, the use of a sustained
release preparation may exacerbate gastric irritation
and chemical instability in gastric fluid.
6. Drug absorption differences in various
gastrointestinal segments
In general, drug absorption is moderately slow in
the stomach, rapid in the small intestine, and
sharply declining in the large intestine.
Compensation for changing absorption
characteristics in the gastrointestinal tract may be
important for some drugs. For example, it is
rational for a delivery system to pump out the drug
much faster when the system reaches the distal
segment of the intestine, to avoid the entombment
of the drug in the feaces(Burnside et al.,2003).