›



:



 
 


  › ›› 

 
  › Y
INTRODUCTION

CIRCADIAN RHYTHM

CHRONOPHARMACEUTICAL ACTIVE AGENT

METHODOLOGIES FOR PULSATILE SYSTEM

RECENT ADVANNCES

MARKETED EXAMPALES

CONCLUSION

REFERENCES

‡
Y 

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.

  !

Pulsatile drug delivery system is to achieve the

chronotherapy„
¯ Advantages :

˜ Õ

 


 


˜

˜

˜



˜ 




˜
















˜



 







˜







˜




 




˜






 „


 g ulsatile release :

A Æ
 !

 
B Æ



 
 !
C Æ








 


 !„
"
?
 "„CHRONO HARMACO O Y:

 




 





„

6.CHRONOKIN TICS:





 









 

„

7.BIO O ICA RHYTHMS

 
#

‡
 $
%
  
#
‡
 $
  
#

‡
 $

&
 Sleep disorder
eptic ulcer
pilepsy Aponea
Osteoarthritis Asthma

Allergic Rhinitis
Angina pectoris
Cardiac arrest
Stroke

Ú
 "#$ #%"&
#!& %'#  !   %''+ ''+
!''+
,''+ -''+
() ' *#& ,''+
&,#''+ .!''+ ,#''+ .''+
/,#''+
''+
()"&& 01#'+ #+ #%' 
+ #' 

' %1 2' ' *#& 1',+ .,+ .&',+ '31+ .#,+
4#,1'
 2#& ,,#'+ 5%,#'+
#,#'+
3,#'+ #',#'
Y) # ,# "&& #&#+ -&#
%#  & $# 2'#23+ ,1+ 0,1+
#+
#&1
#" #& '$ #$')##+ &&#)#+ &&#)6)
1#
2#& '+
#3&+
2'1+ #1+ ›%1
#,#%&&
  # #%"& &,'+ /','+ 
+   + '  + /#%  +
2#/
& ''%& %# %'+ 2'+ ,#+
' + .#,#+ #"2
'"2
6
 




'
 

Õ



()

'
 
     
     

*   
  
+
,Õ 
--%+'
Õ-,
+'
((
 ,,#!' 

#,##$ 17
#,##$  &8#'
 &"#1 2#) # 2#2#,$
,2#1 % '
 2'"$

›ept. 01, 1982 Theophylline Uniphyl; CONTIN Asthma/increased

extended release bronchoconstriction
tablets in morning
Oct. 15, 1986 Famotidine Pepcid; tablets Physico-chemical Ulcer/increased
modification of API gastric acid secretion
in evening
Dec. 23, 1991 ›imvastatin Zocor; Tablets Physico-chemical Hypercholesterolemia
modification of API /increased cholesterol
synthesis overnight
Feb. 26, 1996 Verapamil HCl Covera-H›; extended ORO› Hypertension/increase
release tablets d BP early morning
Nov. 25, 1998 Verapamil HCl Verelan PM; extended CODA› Hypertension
release capsules
Feb. 06, 2003 Diltiazem HCl Cardizem LA; CEFORM Hypertension
verapamil HCl extended
release tablets
Mar. 12, 2003 Propranolol HCl InnoPran XL DIFFUCAP› Hypertension
verapamil HCl extended
release capsules (‡
'

 









 








  
:



  


(
1. Howard N. E. ›tevens: Pulsincap and hydrophilic sandwitch capsules, Modified Release
Drug Delivery Technology, Vol.126, Marcel Dekker, Inc., 257-261
2. Arora ›, Ali.J, Ahuje.A: Pulsatile drug delivery systems: An approach for controlled drug
delivery, Indian J. Pharm. ›ci., 2006, 68(3): 295-300.
3. Bussemer.T, Roland B: Multiparticulate Pulsatile Drug delivery ›ystems,
Microencapsulation Methods and Industrial Applications Ed.2 Edited by: ›imon Benita.
Published by: Taylor and Francis. 79-84
4. A.V. Gothoskar, A.M. Joshi, and N.H. Joshi, Pulsatile Drug Delivery ›ystems: A Review,
www.drugdeliverytech.com
5. #& 2 ›2#% Colon Targeted Pulsatile Drug Delivery : A Review; Indian J. Pharm.
›ci., 2007, 45(3): 95-100.
6. ›risagul ›ungthongjeen, ›atit 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 › Belgamwar, Madhuri V Gaikwad, Ganesh B Patil, ›anjay ›urana; Pulsatile drug
delivery system; Asian Journal of Pharmaceutics - July-›eptember 2008
8. ›achin ›urvase and Neeraj Kumar; PUL›ATILE DRUG DELIVERY: CURREN
›CENARIO; j. of Current Research & Information on Pharmaceutical ›ciences 2008 88(7),
56-66.

(

11. Till Bussemer, Roland A. Bodmeier; Drug Delivery: Pulsatile ›ystems; Encyclopedia
of PHARMACEUTICAL TECHNOLOGY; Editor - James ›warbrick, Third Edition ;
VOLUME 2 1297-1320.
12. Andrea Gazzaniga *, Luca Palugan, Anastasia Foppoli, Maria Edvige ›angalli; 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, ›ongqing 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 ›. J. Pharm. ›ci. 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 ›. ›atarkar, J. Zach Hilt; Magnetic hydrogel nanocomposites for remote
controlled pulsatile drug release; Journal of Controlled Release 130 (2008) 246±251.
("
(?