3. INTRODUCTION Pulsatile drug delivery systems (PDDS) are gaining importance as they deliver a drug at time and site specific manner resulting in improved therapeutic efficacy as well as compliance. Chronopharmacotherapy designed according to the circadian rhythm of the body Ecofriendly Intelligent drug delivery systemcapable of adjusting drug release rates in response to a physiological need.
4. NECESSITY OF PULSATILE DRUGDELIVERY SYSTEMS Follow circadian rhythm, Protection from gastric environment, To achieve localized action, First-pass metabolism can be overcome.
5. DISEASES THAT REQUIRE PULSATILE DRUG DELIVERYDisease Chronological behavior Drugs usedPeptic ulcer Acid secretion is high in the H2blockers afternoon and at night.Attention deficit syndrome Increase in DOPA level in Methylphenidate afternoonCardiovascular diseases BP is at its lowest during the Nitroglycerin, calcium sleep cycle and rises steeply channel, during the early morning blocker, ACE inhibitorsAsthma Precipitation of attacks Β2 agonist, Antihistamines during night or at early morning.Arthritis Level of pain increases at NSAIDs, Glucocorticoids nightDiabetes mellitus Increase in the blood sugar Sulfonylurea, Insulin level after mealHypercholesterolemia Cholesterol synthesis is HMG CoA reductase, generally higher during Inhibitors night than day time.
6. METHODOLOGIES I. Time controlled pulsatile release II. Internal Stimuli induced A. Thermo-Responsive Pulsatile release B. Chemical stimuli induced pulsatile systems III. External stimuli induced IV. Multiparticulate pulsatile drug delivery system V.Pulsatile release systems for vaccine and hormone products
7. I) TIME CONTROLLED PULSATILERELEASE Delivery system provided with erodible coating layers Delivery system provided with ruputable coating layer Capsule shaped system provided with release controlling plugThese can be formulated as Tablets, Capsules, Pellets, Spheres, Beads, Films, Hydrogels
8. II) INTERNAL STIMULI INDUCED PULSATILERELEASE SYSTEM Temperature–induced pulsatile release Inflammation-induced Pulsatile Release pH Sensitive Drug Delivery System Glucose-responsive Insulin Release DevicesIII) EXTERNALLY REGULATED PULSATILE RELEASE Magnetic induces release Ultrasound induces release Electric field induces release Light induces release
9. IV) MULTIPARTICULATE PULSATILE DRUGDELIVERY SYSTEM Reservoir systems with rupturable polymeric Coatings Reservoir systems with soluble or eroding polymer coatings Floating multiparticulate pulsatile systemsV) PDDS FOR VACCINE AND HORMONE PRODUCTS PDDS offer the possibility of single-shot vaccines if initial booster release of the antigen can be achieved from one system in which timing of booster release is controlled.
10. ADVANTAGES Extended daytime or nighttime activity Reduced dose size, dosage frequency Drug targeting to specific site. Drug loss is prevented by extensive first pass metabolism . Predictable, reproducible and short gastric residence time Less inter- and intra-subject variability Improved bioavailability, stability, patient comfort and compliance Reduced adverse effects and improved tolerability Limited risk of local irritation No risk of dose dumping Flexibility in design Achieve a unique release pattern Extend patent protection, globalize product, and overcome competition
11. LIMITATIONS Lack of manufacturing reproducibility and efficacy Large number of process variables Multiple formulation steps Higher cost of production Need of advanced technology Trained/skilled personal needed for manufacturing
13. CONCLUSIONThere is a constant need for new delivery systems that canprovide increased therapeutic benefits to the patients. Pulsatiledrug delivery is one such system that, by delivering drug atthe right time, right place, and in right amounts, holds goodpromises of benefit to the patients suffering from chronicproblems like arthritis, asthma, hypertension, etc. PDDS caneffectively release drug according to bodys circadian clockgiving release of drug after a specified time lag. With increasein technological advancement and better design parametershurdles can be overcome in the near future and more numberof patients will be greatly benefited by these systems.
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