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PULSATILE DRUG DELIVERY

SUBMITTED BY

PRASHANT H. KHADE

M.PHARM (IInd SEM)

GUIDED BY

MRS. SWATI MUTHA

ASST. PROF.(PHARMACEUTICS)

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ContentsINTRODUCTION

CIRCADIAN RHYTHM

CHRONOPHARMACEUTICAL ACTIVE AGENT

RECENT ADVANNCES

MARKETED EXAMPALES

CONCLUSION

REFERENCES

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INTRODUCTION1] 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] Pulsatile release :

A = release of drug as a “pulse” after a lag time, B = delivering the drug rapidly and completely after a “lag time” aC =constant drug release over a prolonged period of time after a “lag time”.

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5.CHRONOPHARMACOLOGY: The study of how biological rhythm affects the medication.

6.CHRONOKINETICS:

Refers to biologic rhythm effects on drug absorption , distribution, and elimination.

7.BIOLOGICAL RHYTHMS Circadian rhythm (about 24 hr) Ultradian rhythm (Less than 24 hr) Infradian rhythm (more than 24 hr)

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CIRCADIAN RHYTHM

Sleep disorderAponeaAsthma

Allergic RhinitisAngina pectorisCardiac arrestStroke

Peptic ulcerEpilepsyOsteoarthritis

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Chronotherapeuticaly active drugs

Category Drugs

Cardiovascular active andΒ- blockers

Acebutolol, Atenolol, Bevantolol, Bopindolol, Labetolol, Mepindolol, Bisoprolol, Nebivolol, Metoprolol, Nadolol, Oxprenolol, Pindolol,

Β-agonists Xamoterol, Midodrine, Terbutaline (IOP), Adrenaline (IOP)

Calcium channel blockers Amlodipine, Nifedipine, Nisoldipine, Diltiazem, Nitrendipine, Verapamil

ACE inhibitors Captopril, Quinapril, Perindopril, Benazepril, Trandolapril.

AT1- receptor antagonists Irbesartan, Losartan

Diurectics Hydrochlorothiazide, Indapamide, Xipamide, Piretanide, Torasemide

Organic nitrates Glyceryl-trinitrate, Isosorbide-dinitrate, Isosorbide-5-mononitrate

Others Clonidine, Prazosin, Phentolamine, Indoramine, Sodium nitroprusside

Anticancer drugs Cisplatin, Oxaliplatin, THP, FUDR, Folic acid, Doxorubicin , Methotrexate

Miscellaneous Tuberculine, Ethanol, Heparin, Placebo, Nadroparine, bright light

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METHODOLOGIES FOR PULSATILE SYSTEM

Time controlled

Stimuli induced

Externally regulated

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RECENT ADVANNCES IN THE PULSATILE DRUG DELINERY

CONTIN®,

OROS®

Chronomodulating infusion pumps

Three dimensional printingPhysic-chemical modification of the API TIMERx®

DIFFUCAPS®

CEFORM®

CODAS®

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MARKETED EXAMPALESFDA approval

dateAPI Propriatory name;

dosage formProprietary

Chrono-pharmaceutical

Technology

Indications/rationale for chronotherapy

Sept. 01, 1982 Theophylline Uniphyl;extended release tablets

CONTIN Asthma/increased bronchoconstrictionin morning

Oct. 15, 1986 Famotidine Pepcid; tablets Physico-chemicalmodification of API

Ulcer/increased gastric acid secretion in evening

Dec. 23, 1991 Simvastatin Zocor; Tablets Physico-chemicalmodification of API

Hypercholesterolemia/increased cholesterol synthesis overnight

Feb. 26, 1996 Verapamil HCl Covera-HS; extendedrelease tablets

OROS Hypertension/increased BP early morning

Nov. 25, 1998 Verapamil HCl Verelan PM; extendedrelease capsules

CODAS Hypertension

Feb. 06, 2003 Diltiazem HClverapamil HCl

Cardizem LA; extendedrelease tablets

CEFORM Hypertension

Mar. 12, 2003 Propranolol HClverapamil HCl

InnoPran XL extendedrelease capsules

DIFFUCAPS Hypertension

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CONCLUSION

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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REFERENCES1. Howard N. E. Stevens: Pulsincap and hydrophilic sandwitch capsules, Modified Release Drug Delivery Technology, Vol.126, Marcel Dekker, Inc., 257-2612. 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. 79-844. A.V. Gothoskar, A.M. Joshi, and N.H. Joshi, Pulsatile Drug Delivery Systems: A Review, www.drugdeliverytech.com5. 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): 147-1597. Veena S Belgamwar, Madhuri V Gaikwad, Ganesh B Patil, Sanjay Surana; Pulsatile drug delivery system; Asian Journal of Pharmaceutics - July-September 20088. 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) 11–1813. Bin Li, JiaBi Zhu , ChunLi Zheng, Wen Gong; A novel system for three-pulse drug ∗release based on “tablets 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) 55—6015. 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): 25-2816. Andrei Dashevsky , Ahmad Mohamad; Development of pulsatile multiparticulate ∗drug delivery system coated with aqueous dispersion Aquacoat® ECD; International Journal of Pharmaceutics 318 (2006) 124–13117. 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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Thank you