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1. IMPLICATIONS OF
CHRONOPHARMACOKINETICS
FOR DRUG DELIVERY
S.SHILPA

2. Deals with the study of the
temporal changes in the
absorption, distribution, metab
olism and elimination due to
time of administration
CHRONOPHARMACOKINETICS

3. WHY STUDY CHRONO- P’KINETICS??
 PK- PD VARY WITH TIME
 Gastric motility: is double in day time than in night
 Plasma protein concentrations are higher in day than in night
 Hepatic blood flow has been shown to be greatest at 8 am and
Metabolism to be reduced during the night
 DRUG TOXICITY CAN BE AVOIDED/ MINIMIZED BY ADMINISTERING
AT A PARTICULAR TIME

5. CYCLIC VARIATIONS OVER TIME
Ultradian rhythms : <20 hrs
Circadian rhythms : 20-28
Infradian rhythms : >28 hrs
Circaseptan : 7 days
Circamensual : 30 days
Circa-annual rhythms : 1 year
BODY RHYTHMS

6. CIRCADIAN RHYTHM
 “Circa” means around &“diem” means day
 Eyes > retina > SCN
 SCN passes the information to pineal gland
>> melatonin hormone
 Exposure of light can change endogenous
circadian pace time of light, duration
wavelength, intensity, which determine circadian
patterns of body

7. EXAMPLES OF CIRCADIAN RYTHM
 WBC count peak at late night
 Haemoglobin and insulin are highest in the afternoon
 BP increases in morning after night sleep, peaks afternoon & decreases during sleep
SLEEP CYCLE

10. CHRONOPHARMACEUTICAL DRUG DELIVERY SYSTEMS
OROS TECHNOLOGY
Osmotic‐controlled Release Oral
delivery System

11. CROSS SECTION OF
DIFFUCAPS
DIFFUCAPS TECHNOLOGY
CHRONOPHARMACEUTICAL DRUG DELIVERY SYSTEMS

12. (A) INTACT UNIT
(B) EROSION OF THE TIME DELAY INSERT PLUGS
(C) DRUG RELEASE
EGALET TECHNOLOGY
CHRONOPHARMACEUTICAL DRUG DELIVERY SYSTEMS
• Offers a delayed release
• System consists of an
impermeable shell
With two lag plugs,
active drug is
sandwiched between
the plugs.

13. APPLICATIONS
 ASTHMA
 Chronotherapy for asthma is aimed at getting maximal effect from
bronchodilator medications during early morning hours.
e.g. Theophylline
 GASTROINTESTINAL DISEASES
 Chronotherapy of peptic ulcers with evening once daily dosing of H2 receptor
antagonist.
e.g. Ranitidine
 ARTHRITIS
 For osteo arthritis Drug will be given in the noon.
 For Rheumatoid arthritis Drug will be effective when taken after the
evening meal
e.g. Ibuprofen

14. APPLICATIONS
 CARDIOVASCULAR DISEASE
 Diseases such as hypertension, heart attack mostly occurs in the morning.
 BP at its lowest during sleep cycle and rises steeply during early morning
awakening period.
 CANCER
 Cancer drugs administer should be timed to cycles of tumour cells making
them more effective against cancer and less toxic to normal tissues.
 Blood flow to tumours and tumour growth rate are greater during
activity phase than rest phase
 By treatment at midnight more tumour cells kill could be achieved with
same dose of active cytotoxic therapy.

15. CONCLUSION
 Importance of biological rhythms in the treatment of diseases
 Selection of the appropriate chronopharmaceutical technology should take into
considerations the application range, the ease of manufacturing, the cost-effectiveness,
and the flexibility in the pharmacokinetic profile.
 Improve patient outcome and optimize disease management in the future.