PULSATILE DRUG DELIVERY SYSTEM

BY

C.V. SAIKRISHNA REDDY

M.PHARM I YEAR

JJ COLLEGE OF PHARMACY

CONTENTS

INTRODUCTION METHODOLOGIES ADVANTAGES LIMITATIONS COMMERCIAL PRODUCTS CONCLUSION REFERENCES

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.

NECESSITY OF PULSATILE DRUG DELIVERY SYSTEMS

Follow circadian rhythm,

Protection from gastric environment,

To achieve localized action,

First-pass metabolism can be overcome.

DISEASES THAT REQUIRE PULSATILE DRUG DELIVERY

Disease Chronological behavior Drugs used

Peptic ulcer Acid secretion is high in the afternoon and at night.

H2blockers

Attention deficit syndrome Increase in DOPA level in afternoon

Methylphenidate

Cardiovascular diseases BP is at its lowest during the sleep cycle and rises steeply during the early morning

Nitroglycerin, calcium channel,blocker, ACE inhibitors

Asthma Precipitation of attacks during night or at early morning.

Β2 agonist, Antihistamines

Arthritis Level of pain increases at night

NSAIDs, Glucocorticoids

Diabetes mellitus Increase in the blood sugar level after meal

Sulfonylurea, Insulin

Hypercholesterolemia Cholesterol synthesis is generally higher during night than day time.

HMG CoA reductase, Inhibitors

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

I) TIME CONTROLLED PULSATILE RELEASE Delivery system provided with erodible coating layers Delivery system provided with ruputable coating layer Capsule shaped system provided with release controlling plug

These can be formulated as Tablets, Capsules, Pellets, Spheres, Beads, Films, Hydrogels

II) INTERNAL STIMULI INDUCED PULSATILE RELEASE SYSTEM

Temperature–induced pulsatile release Inflammation-induced Pulsatile Release pH Sensitive Drug Delivery System Glucose-responsive Insulin Release Devices

III) EXTERNALLY REGULATED PULSATILE RELEASE

Magnetic induces release Ultrasound induces release Electric field induces release Light induces release

IV) MULTIPARTICULATE PULSATILE DRUG DELIVERY SYSTEM

Reservoir systems with rupturable polymeric Coatings Reservoir systems with soluble or eroding polymer

coatings Floating multiparticulate pulsatile systems

V) 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.

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

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

COMMERCIAL PRODUCTS

Pulsys® - amoxicillin - Advancis Pharm Corp Uniphyl – theophylline - Purdue Pharm Pdts L Ritalinβ – methylphenidate – Novartis CODAS® - Verapamil HCl TIMERx® - Oxymorphone PulsincapTM - Dofetilide

 CONCLUSION

There is a constant need for new delivery systems that can provide increased therapeutic benefits to the patients. Pulsatile drug delivery is one such system that, by delivering drug at the right time, right place, and in right amounts, holds good promises of benefit to the patients suffering from chronic problems like arthritis, asthma, hypertension, etc. PDDS can effectively release drug according to body's circadian clock giving release of drug after a specified time lag. With increase in technological advancement and better design parameters hurdles can be overcome in the near future and more number of patients will be greatly benefited by these systems.

 

REFERENCES

1. Janugade BU, Patil SS, Patil SV, Lade PD: Pulsatile drug delivery system for chronopharmacological disorders: an overview. Journal of Pharmacy Research , 2009; 2 (1):133-143.2. http://www.uspharmacist.com/oldformat.asp?url=newlook/files/ Feat/ACF2F15.cfm&pub_id, accesed on 15/9/10.

3.Björm Hemmer. Circadian rhythms and drug delivery. J. Control. Release, 1991, 16: 63-74.

4.B. Lemmer, Chronopharmacokinetics: implications for drug treatment, J. Pharm. Pharmacol., 1999, 51: 887-890.

5.P. Roy, A. Shahiwala. Multiparticulate formulation approach to pulsatile drug delivery: current perspectives. J. Control. Release, 2009, 134:74-80.

6. R. Gurny, H. E. Junginger, N. Peppas, Eds., In; Pulsatile Drug Delivery: Current Application and Future Trends,Wissenschefliche Verlagsgesellschaft, Stuttgart, Germany, 1993, 36.

7.M. M. Massin, K. Maeyns, N. Withofs, et al. Circadian rhythm of heart rate and heart rate variability. Arch. Dis. Child., 2000, 83: 179-182.

8. J. Qureshi, Mohd. Amir, Alka Ahuja et al. Chronomodulated Drug Delivery System of Salbutamol Sulphate for the Treatment of Nocturnal Asthma. Indian J. Pharm. Sci. 2008, 351-356.

THANQ