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PULSATILE DRUG DELIVERY
SYSTEM
(PDDS)
Prepared by: Manoj Paudel
III Semester
Roll No: 124
Department Of Pharmacy
Objectives
 Introduction of PDDS
 Necessities of PDDS
 Types of PDDS
METHODOLOGY
 Review journals
 Assistance from faculty teacher
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
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
 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
 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
 capillary resistance and vascular reactivity are
higher in the morning and decrease later in the
day
 Thus Demands a PDDS
NECESSITIES OF PDDS
 First pass metabolism
 Biological tolerance
 Special chronopharmacological needs
 Local therapeutic need
 Gastric irritation or drug instability in GI tract
Classification of PDDS
PDDS
Internal stimuli
induced
system
Temperature
induced
PH sensitive
Inflammation
induced
Glucose
responsive
Time
Controlled
Externally
regulated
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
Temperature Induced Drug
Release
 Deviation of temperature acts as stimulus and
triggers drug release
 Useful for disease accompanying fever
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.
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
 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.
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.
 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
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
CAPSULAR SYSTEM FOR PULSATILE
RELEASE
Externally Regulated
 Magnetic induces release
 Ultrasound induces release
 Electric field induces release
 Light induces release
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.
References
1. http://media.wix.com/ugd/5ccba3_0b3e45df793cb580b
1302d85830accb7.pdf
2. http://www.ijpbs.net/vol-2_issue-
3/pharma_science/39.pdf

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PDDS for Circadian Disorders

  • 1. PULSATILE DRUG DELIVERY SYSTEM (PDDS) Prepared by: Manoj Paudel III Semester Roll No: 124 Department Of Pharmacy
  • 2. Objectives  Introduction of PDDS  Necessities of PDDS  Types of PDDS
  • 3. METHODOLOGY  Review journals  Assistance from faculty teacher
  • 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
  • 22.
  • 23. CAPSULAR SYSTEM FOR PULSATILE RELEASE
  • 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.

Editor's Notes

  1. when gastric motility and emptying are slower, drug disintegration, dissolution, and absorption may be slower
  2. 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).