SUBMITTED BY PRASHANT H. KHADE M.

PHARM (IInd SEM)

GUIDED BY

MRS. SWATI MUTHA
ASST. PROF.(PHARMACEUTICS)
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INTRODUCTION CIRCADIAN RHYTHM
CHRONOPHARMACEUTICAL ACTIVE AGENT
METHODOLOGIES FOR PULSATILE SYSTEM

RECENT ADVANNCES MARKETED EXAMPALES CONCLUSION REFERENCES
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1] Defination: Pulsed or Pulsatile drug release is defined as the rapid and transient release of certain amount of drug molecules within a short time of period immidietly after a predetermined off release period.

2] Objective : Pulsatile drug delivery system is to achieve the chronotherapy.

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3] Advantages : 
Extended daytime or nighttime activity, 
Reduced side effects , Reduced dosage frequency, Reduction in dose size, Improved patient compliance, Lower daily cost to patient due to fewer dosage units are required by the patient in therapy, Drug adapts to suit circadian rhythms of body functions or diseases, Drug targeting to specific site like colon, Protection of mucosa from irritating drugs, Drug loss is prevented by extensive first pass metabolism.
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4]

ulsatile release :

A = release of drug as a ³pulse´ after a lag time, B = delivering the drug rapidly and completely after a ³lag time´ a C =constant drug release over a prolonged period of time after a ³lag time´.
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5.CHRONO HARMACO O Y: The study of how biological rhythm affects the medication. 6.CHRONOKIN TICS: Refers to biologic rhythm effects on drug absorption , distribution, and elimination. 7.BIO O ICA RHYTHMS Circadian rhythm (about 24 hr) Ultradian rhythm (Less than 24 hr) Infradian rhythm (more than 24 hr)
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eptic ulcer pilepsy Osteoarthritis

Sleep disorder Aponea Asthma

Allergic Rhinitis Angina pectoris Cardiac arrest Stroke

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Category
Cardiovascular active and - blockers -agonists Calcium channel blockers ACE inhibitors AT1- receptor antagonists Diurectics Organic nitrates Others Anticancer drugs Miscellaneous

Drugs
Acebutolol, Atenolol, Bevantolol, Bopindolol, Labetolol, Mepindolol, Bisoprolol, Nebivolol, Metoprolol, Nadolol, Oxprenolol, Pindolol, Xamoterol, Midodrine, Terbutaline (IOP), Adrenaline (IOP) Amlodipine, Nifedipine, Nisoldipine, Diltiazem, Nitrendipine, Verapamil Captopril, Quinapril, Perindopril, Benazepril, Trandolapril. Irbesartan, Losartan Hydrochlorothiazide, Torasemide Glyceryl-trinitrate, mononitrate Clonidine, Prazosin, nitroprusside Indapamide, Xipamide, Piretanide, Isosorbide-5Sodium

Isosorbide-dinitrate, Phentolamine,

Indoramine,

Cisplatin, Oxaliplatin, THP, FUDR, Folic acid, Doxorubicin , Methotrexate Tuberculine, Ethanol, Heparin, Placebo, Nadroparine, bright light

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Time controlled

Stimuli induced

Externally regulated
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CONTIN®, OROS® Chr l ti i f si l ri ti ific ti f the API s

Three i e si Physic-che ic l TIMERx® DIFFUCAPS® CEFORM® CODAS®

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FDA approval date

API

Propriatory name; dosage form

Proprietary Chronopharmaceutical Technology CONTIN

Indications/rationale for chronotherapy

Sept. 01, 1982

Theophylline

Uniphyl; extended tablets Pepcid; tablets

release Physico-chemical modification of API Physico-chemical modification of API OROS

Asthma/increased bronchoconstriction in morning Ulcer/increased gastric acid secretion in evening Hypercholesterolemia /increased cholesterol synthesis overnight Hypertension/increase d BP early morning Hypertension Hypertension

Oct. 15, 1986

Famotidine

Dec. 23, 1991

Simvastatin

Zocor; Tablets

Feb. 26, 1996 Nov. 25, 1998 Feb. 06, 2003

Verapamil HCl Verapamil HCl Diltiazem HCl verapamil HCl Propranolol HCl verapamil HCl

Covera-HS; extended release tablets

Verelan PM; extended CODAS release capsules Cardizem extended release tablets InnoPran extended release capsules LA; CEFORM

Mar. 12, 2003

XL DIFFUCAPS

Hypertension

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Sustained release formulations are not efficient in treating the especially diseases with chronological pathopysiology, for which, Pulsatile drug delivery is beneficial.

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1. Howard N. E. Stevens: Pulsincap and hydrophilic sandwitch capsules, Modified Release Drug Delivery Technology, Vol.126, Marcel Dekker, Inc., 257-261 2. Arora S, Ali.J, Ahuje.A: Pulsatile drug delivery systems: An approach for controlled drug delivery, Indian J. Pharm. Sci., 2006, 68(3): 295-300. 3. Bussemer.T, Roland B: Multiparticulate Pulsatile Drug delivery Systems, Microencapsulation Methods and Industrial Applications Ed.2 Edited by: Simon Benita. Published by: Taylor and Francis. 79-84 4. A.V. Gothoskar, A.M. Joshi, and N.H. Joshi, Pulsatile Drug Delivery Systems: A Review, www.drugdeliverytech.com 5. Mrs. Rathod Shruti: Colon Targeted Pulsatile Drug Delivery : A Review; Indian J. Pharm. Sci., 2007, 45(3): 95-100. 6. Srisagul Sungthongjeen, Satit Puttipipatkhachorn, Ornlaksana Paeratakul, Andrei Dashevsky and Roland Bodmeier : Development of pulsatile release tablets with swelling and rupturable layers, Journal of Controlled Release, 2004, 95(2): 147-159 7. Veena S Belgamwar, Madhuri V Gaikwad, Ganesh B Patil, Sanjay Surana; Pulsatile drug delivery system; Asian Journal of Pharmaceutics - July-September 2008 8. Sachin Survase and Neeraj Kumar; PULSATILE DRUG DELIVERY: CURREN SCENARIO; j. of Current Research & Information on Pharmaceutical Sciences 2008 88(7), 56-66.
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11. Till Bussemer, Roland A. Bodmeier; Drug Delivery: Pulsatile Systems; Encyclopedia of PHARMACEUTICAL TECHNOLOGY; Editor - James Swarbrick, Third Edition ; VOLUME 2 1297-1320. 12. Andrea Gazzaniga *, Luca Palugan, Anastasia Foppoli, Maria Edvige Sangalli; Oral pulsatile delivery systems based on swellable hydrophilic polymers; European Journal of Pharmaceutics and Biopharmaceutics 68 (2008) 11±18 13. Bin Li, JiaBi Zhu , ChunLi Zheng, Wen Gong; A novel system for three-pulse drug release based on ³tablets in capsule´ device; International Journal of Pharmaceutics 352 (2008) 159±164. 14. Yao LIU, Songqing LIU,* and Qing DAI; Design and Evaluation of pH-Independent Pulsatile Release Pellets Containing Isosorbide-5-mononitrate; Chem. Pharm. Bull. 57(1) (2009) 55²60 15. Vijaya Kumar B* , Nagaraj B , Agaiah B , Rambhau D ; Design and In Vitro Evaluation of Chrono Modulated Theophylline Tablets S. J. Pharm. Sci. 1(1&2): 25-28 16. Andrei Dashevsky , Ahmad Mohamad; Development of pulsatile multiparticulate drug delivery system coated with aqueous dispersion Aquacoat® ECD; International Journal of Pharmaceutics 318 (2006) 124±131 17. Bi-Botti C. Youan; Chronopharmaceutics: gimmick or clinically relevant approach to drug delivery?; Journal of Controlled Release 98 (2004) 337± 353. 18. Nitin S. Satarkar, J. Zach Hilt; Magnetic hydrogel nanocomposites for remote controlled pulsatile drug release; Journal of Controlled Release 130 (2008) 246±251.
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