novel drug delivery system

1. Computation of Desired Release rate and dose for
CRDDS Pharmacokinetic Design For Release
SUBMITTED BY: SUBMITTED TO:
NEERAJ (42/MIP/SPS/23) Dr. SUSHAMA TALEGAONKAR
M. PHARMACY(INDUSTRIAL PHARMACY)

2. Content
1. Controlled Drug Delivery System
2. Advantages of CRDDS
3. Computation Of Desired Release Rate
4. Dose for CDDS
5. Pharmacokinetic Design

3. Controlled Drug Delivery System
Controlled drug delivery is that type of system which release the
medicaments from the dosage form at a predetermined specified rate
for locally or systemically for a specified period of time.
Controlled release drug delivery employs drug-encapsulating devices
from which therapeutic agents may be released at controlled rates for
long periods of time, ranging from days to months.

4. The main advantages of controlled drug delivery
are:
 Low amount of administered doses;
 Less gastrointestinal side effects;
 Less dosing frequency;
 Improved patient acceptance & compliance;
 Less ups & downs in plasma drug concentration;
 Highly uniform drug action & effect;
 Enhanced efficacy & drug safety.

5. COMPUTATION OF DESIRED RELEASE
RATE
The computation of the desired release rate for a
Controlled Drug Delivery System (CDDS)
involves considering factors such as drug
properties, desired therapeutic effect, and the
chosen delivery mechanism. Mathematical model,
Higuchi's model, are often used to estimate release
rates.

6. Cont..
Release rate equation :
Q = A √D(2C - Cs) Cs t
Where,
Q= Amount of drug released in time t per unit area A,
C= Initial drug concentration,
Cs= Drug solubility in the matrix media,
D= Diffusion coefficient

7. Dose for CDDS
To maintain the steady state at a desired concentration level two
factors are important.
1. Dose
2. Dosing Interval
The formula for dose of the drug in CRDDS is:

8. Cont….
Where,
F= Total amount of drug absorbed
T= Dose of the drug
Css= Steady state plasma concentration
D= Dosing interval
Cl= Clearance

9. Examples
How much dose of a controlled release preparartion is required
at every 12 hours to attain a steady state plasma concentration
of 2mg/l. The clearance of the drug is 18 L per hour and 90%
of drug is absorbed .
Solution:
Cl= 18L/h
Css= 2mg/L
F= 90%
D= 12h

10. Cont…
0.9 x T = 2 x 12 x 18
T = 432/0.9
T= 480 mg

11. Example
A 600 mg of sustained release product was given for every
12 hr. If the volume of distribution is 20 L, elimination rate
constant is 0.5 /h and 90 % of drug is absorbed, calculate
the average steady state plasma concentration.
Solution:
T= 600mg
Vd = 20L
F= 90%
D= 12h
Ke= 0.5/h

12. Cont….
0.9 x 600 = Css x 12 x 0.5 x 20
Css = 540/ 120
Css = 4.5 mg/l

13. Pharmacokinetic principles in design of CRDDS:-
• The controlled-release dosage forms are so designed that they release the
medicament over a prolonged period of time usually longer than the typical dosing
interval for a conventional formulation.
• The drugs used in CRDDS should be closely monitored for steady state conc.
• Rate controlling step is always rate of release of drug from the formulation and
should ideally be lower than absorption rate.
• Rate of release of drug ideally should be zero order or near zero order.

14. Drug release patterns of CRDDS:-
• There are 4 major types of drug release characteristics from
controlled release formulation:-
1. Slow zero order.
2. Slow first order.
3. Initial rapid dose then zero order.
4. Initial rapid dose then slow first order.

15. Schematic representation of four major types of drug release
characteristics from controlled-release formulations
Bramankar D.M., Jaiswal Sunil et. al, “Biopharmaceutics and Pharmacokinetics- A treatise”,
Published by- Vallabh Prakashan, 3rd Edition, 2020,

16. 1) Slow Zero order:-
• If the drug released from controlled-release formulations is stable in
fluids at the absorption site, has similar absorption efficiency from all
absorption sites and is absorbed rapidly and completely after its
release, then, its rate of appearance in plasma will be governed by
its rate of release from the controlled-release formulation.
• Thus, when the drug release follows zero-order kinetics, absorption
will also be a zero-order process and concentration of drug in plasma
at any given time.
• Zero-order release systems are thus ideal controlled delivery
formulations.

17. 2) Slow First Order:-
• Such systems are easier to design but are inferior to zero-order
systems especially when they are meant for oral use.
• This is because with first-order release characteristics, smaller and
smaller amounts of drug are released as time passes.
• Secondly, as the formulation advances along the GIT, the absorption
efficiency generally decreases due to a number of reasons like
decreased intestinal surface area, increased viscosity and decreased
mixing.

18. 3) Initial rapid dose then zero order:-
• With such formulations, an initial dose is rapidly released
(burst-effect) for immediate first-order availability while the
remaining amount is released and absorbed at a slow zero-
order rate.
• Such a formulation is ideally suited for drugs with long t½ in
which cases attainment of plateau would otherwise take a
long time.
• The slow release component should ideally release the drug
when drug component from fast component are at peak.

19. 4) Initial rapid dose then slow first order:-
• As in the previous case, to obtain the desired plateau, the slow
release component, Dm should start releasing the drug:1.
• When the peak has been attained with rapid release dose, DI;
this requires DM >>DI which results in wastage of drug since
the absorption efficiency reduces as time passes and dosage
form descends down the GIT.
• When all of the DI has been released; this requires relatively
small DM and therefore less drug wastage and better sustained
levels despite fluctuations in drug levels.

20. Reference
 https://www.youtube.com/watch?v=bFZBXof2OR4
 Bramankar D.M., Jaiswal Sunil et. al, “Biopharmaceutics and Pharmacokinetics- A
treatise”, Published by- Vallabh Prakashan, 3rd Edition, 2020
 SUVAKANTA DASH, PADALA NARASIMHA MURTHY , LILAKANTA NATH and
PRASANTA CHOWDHURY “KINETIC MODELING ON DRUG RELEASE FROM
CONTROLLED DRUG DELIVERY SYSTEMS” Acta Poloniae Pharmaceutica ñ Drug Research,
Vol. 67 No. 3 pp. 217ñ223, 2010

21. THANK YOU