CDDS ( Control drug delivery system)
Presented by Under the Guidance of
Vivek Kumar (1st Semester) Prof.(Dr) Jyotirmaya Sahoo
[Link] Pharmaceutics Dean School of Pharmacy
Department of Pharmaceutics
School of Pharmacy
Content
1. Drug Delivery system
2. Basic concept of Sustained release(SR) and Controlled Release(CR)
3. Rationale of Drug
4. Advantages and Disadvantage of CR/SR
5. Factor influencing formulation and action of (CR ) and (SR)
6. Approaches and Mechanism for formulation of CR/SR
7. Reference
Drug Delivery System
Definition- Drug delivery system is a mode, module and mechanism essentially involved in
the development of control or site specific.
Conventional drug delivery often requires multiple daily doses, leading to fluctuations in
plasma drug concentration (peaks & troughs), poor compliance, and possible side effects.
To overcome this, modified release systems like Sustained Release (SR) and Controlled Release
(CR) formulations were developed.
Oxycodone (chronic pain), Verapamil (Hypertension), Divalproex (epilepsy).
Basic concept of Sustained release(SR) and
Controlled Release(CR)
1.) Sustained Release
Sustain release dosage form- is defined as the type of dosage form in which a portion i.e. (initial
dose) of the drug is released immediately, in order to achieve desired therapeutic response more
promptly, and the remaining(maintenance dose) is then released slowly there by achieving a
therapeutic level which is prolonged, but not maintained constant.
Example-Oxycodone (chronic pain), Verapamil (Hypertension), Divalproex (epilepsy).
2) Control Release
It means the drug delivery system that achieve and ensure the slow release of drug over and
extended for prolonged period of time at constant release (zero order) and at predetermined rate
to attain and maintain therapeutically effective level.
Example- Bupropion ( Depression, smoking ), Prazosin (Hypertension ), Metoprolol
(Hypertension).
Rationale of Drug
Rationale means reason for development
Rationale:-
1) To extend the duration of action of the drug.
2) To avoid undesirable local action.
3) To increase rate and extent of absorption.
And the immediate release drug delivery system lack some feature like Dose maintenance,
Controlled release rate and Site targeting.
Advantages of CR and SR
1. Better Patient compliance
2. Employ less total drug
3. Improve efficiency in treatment by reducing fluctuation in drug level and improve
bioavailability of some drug.
4. Reduction in Healthcare cost
5. Avoidance of Non targeted drug Receptor
6. Reduction in total drug usage when compared with conventional therapy
7. Reduction in frequency of drug administration
Disadvantages of CR and SR
1.) Decrease in systemic availability in comparison to immediate release conventional dosage
form may be due to incomplete release.
2.) Dose dumping (Can increase in concentration of drug).
3.) Retrieval of drug is difficult in case of toxicity, poisoning, hypersensitivity
4.) Delay onset of action.
5). Cost per unit dose is higher when compared with conventional doses
Factor influencing formulation and action of
(CR ) and (SR)
A. Physiological property
1). Molecular size and diffusivity-
• Larger molecules more than 400D rate of movement slower as well create problem during diffusion.
But in case of Smaller molecules have size less than 400D easily diffused in membrane.
2.) Aqueous Solubility
• For a drug to be absorbed it must be dissolved in the aq. phase surrounding the site of administration.
• Most of the drug which is used in formulation in drug its strong acidic and basic in nature and its
easily soluble in medium.
• But in case of weak acidic and basic drug solubility is less we need to convert it into salt form for the
better solubility.
3. Partition Coefficient
Through partition coefficient we can identify the nature of drug whether its lipophilic or
hydrophilic in nature.
4.) Drug Pka
• Pka value decide the ionization constant of drug
• Higher the Pka Value higher the ionization of the drug
• When the drug is ionic, rate of absorption is slow and rate of dissolution is more
• If the drug is non ionic, rate of absorption is higher as well the rate of dissolution is less
5.) Drug Stability
• CRDDS works well with medications that are stable in acid/base, enzymatic breakdown, and
other gastric fluids.
• It is not appropriate for controlled release formulations if the medicine breaks down in the
stomach and small intestine because this would reduce the bioavailability of drug of concern
6.) Protein Binding
• The drug-protein complex act as a reservoir in plasma for the drug.
• Drug showing high plasma protein binding are not a good candidate for CRDDS because
Protein binding increases the biological half-life. So, there is no need to sustain the drug
release.
B.) Biological property
1. Absorption-
It is the process by which a drug moves from site of administration into the blood stream.
The various factors like aqueous solubility, log P etc, which affect the absorption of drugs.
2.) Dose Size-
The CRDDS must have a higher dose than a traditional dosage form because it was designed to do away with
repetitive dosing. However, the dose to be used in CRDDS is indicated by the dose used in conventional dosage
form. The sustained dosage volume ought to be as high as in accordance with the acceptance requirements.
3.) Therapeutic window
• The drugs with narrow therapeutic index are not suitable for CRDDS.
• Dose dumping and eventual toxicity would result from the delivery system's inability to
regulate release.
4) Metabolism.
Drug those are significantly metabolised before absorption either in lumen or in the tissue
intestine can decrease in the absorption.
For a drug to be a candidate for sustain release dosage from it should have low half life, larger
therapeutic window.
Approaches and its Mechanism for formulation of
CR/SR
1. Dissolution controlled release
• Encapsulation Dissolution control
• Seed or granule coated
• Micro encapsulation
• Matrix Dissolution control
2. Diffusion controlled release
• Reservoir type devices
• Matrix type devices
4. Ion exchange resins
5. Osmotically controlled release
1.) Dissolution Release
Dissolution is defined as solid substance solubilized in a given solvent. It is a rate
determining step when liquid is diffusing from solid.
Formula use in dissolution release
Noyes Whitney Equation
dc/dt = kD.A (Cs – C)
• Types of Dissolution release
a) Reservoir type ( Encapsulation)
b) Matrix type
a) Reservoir type
In the reservoir type drug delivery systems, drug is encapsulated in the drug reservoir
compartment whose drug releasing surface is covered by a rate controlling polymeric
membrane .
Example- Polyethylene glycol, polymethylene acrylate, waxes etc
b.) Matrix type
In the matrix-type drug delivery system the drug is homogeneously dispersed in the lipophilic
or hydrophilic polymer matrix .
The drug dispersion in the polymer matrix may introduced by any of following process:
• Blending finely grounded drug particle with viscous liquid polymer
• Mixing drug solid with a melted polymer
• It can also fabricated by dissolving the drug and the polymer in a common solvent, followed
by solvent evaporation, at an elevated temperature
Example- wax, beeswax, carnauba etc.
2.) Diffusion controlled release
It is a significant absorption mechanism that doesn't require any energy.
In this process, which is exactly proportional to the concentration gradient across the
membrane, drug molecules diffuse from an area of greater concentration to one of lower
concentration until equilibrium is reached.
Within this system Its diffusion through a water-insoluble polymer determines the release rate.
Two types of diffusion system: -
a.) Reservoir diffusion system
b.) Matrix diffusion system
a.) Reservoir diffusion system
• Another name for it is a laminated matrix device.
• A polymer can be applied by coating or microencapsulation to this hollow device, which
has an inner core encircled by a membrane that is insoluble in water.
• The drug's ability to partition into membranes is the rate-controlling mechanism.
• exchange through diffusion with the fluid that surrounds the medication.
b.) Matrix diffusion system
A matrix is a solid dosage form where the drug is dispersed throughout an inert polymer or
lipid material.
The polymer matrix does not dissolve (insoluble), but allows diffusion of drug out of pores or
channels created by penetration of fluid.
The release rate is controlled mainly by the diffusion path length of the drug through the
matrix.
3.) ION exchange
• Ion exchange resins are cross-linked water insoluble polymers carrying ionizable functional
groups.
• These resins are used for taste masking and controlled release system.
• The formulations are developed by embedding the drug molecules in the ion-exchange resin
matrix and this core is then coated with a semi permeable coating material such as Ethyl
Cellulose.
• This system reduced the degradation of drug in GIT.
Reference
1. Industrial Pharmacy, fourth edition, Lachman Lieberman’s
2. Controlled drug delivery by S.P. Vyas and R.K. Khar