INTRODUCTION

Controlled drug delivery is one which delivers the drug

at a predetermined rate, for locally and systemically
,for a specified period of time.
Continuous oral delivery of drugs at predictable
&reproducible kinetics for predetermined period
through out the course of GIT.
Difference between sustained and controlled release
CDDR follows the zero order and concentration remain
constant and in sustained release follows the first
order of kinetics where concentration varies with time
to time.
ADVANTAGES
1) Reduction in frequency of drug administration
2) Improved patient compliance
3) Reduction in drug level fluctuation in blood
4) Reduction in total drug usage when compared with
conventional therapy
5) Reduction in drug accumulation with chronic therapy
6) Reduction in drug toxicity (local/systemic)
7) Stabilization of medical condition (because of more uniform
drug levels)
8) Improvement in bioavailability of some drugs because of
spatial control
9) Economical to the health care providers and the patient
DISADVANTAGES
1) Delay in onset of drug action
2) Possibility of dose dumping in the case of a poor formulation strateg
3) Increased potential for first pass metabolism
4) Greater dependence on GI residence time of dosage form
5) Possibility of less accurate dose adjustment in some cases
6) Cost per unit dose is higher when compared with conventional doses
7) Not all drugs are suitable for formulating into ER dosage form
DRUG SELECTION CRITERIA FOR ORAL SUSTAINED AND
CONTROLLED DRUG DELIVERY SYSTEM

1. Physicochemical properties of drug

2. Pharmacokinetic properties of drug
3. Pharmacodynamic properties of drug
Application of SR and CRDDS in following drug delivery
system
a. Oral controlled drug delivery system
b. GRDDS
c. Ocular drug delivery system
d. Trasdermal drug delivery system
e. Intestinal drug delivery system
f. colonic drug delivery system
Physicochemical properties of drug
1. Mol.wt of drug
2. Aqueous solubility
3. Partition coefficient of drug
4. Drug stability
5. Mechanism and site of action
6. Route of administration
Pharmacokinetic properties of drug
1. Absorption rate
2. Elimination half life
3. Rate and extent of metabolism
4. Dosage form index
5. Plasma protein binding
Pharmacodynamic properties of drug

1. Therapeutic index or range

2. Plasma concentration response relation
BIOPHARMACEUTIC AND PHARMACOKINETIC ASPECTS IN
THE DESIGN OF CONTROLLED RELEASE PER ORAL DRUG
DELIVERY SYSTEMS
Controlled release drug delivery systems are dosage forms from which
the drug is released by a predetermined rate which is based on a
desired therapeutic concentration and the drug’s pharmacokinetic
characteristics
1) Biological half-life (t ½) The shorter the t ½ of a drug the larger will
be the fluctuations between the maximum steady state concentration
and maximum steady state concentration upon repetitive dosing. Thus
drug product needs to be administered more frequently.
2)Minimum effective concentration (MEC) If a minimum effective
concentration, MEC is required either frequent dosing of a
conventional drug product is necessary or a controlled release
preparation may be chosen.
3)Dose size and Extent of duration The longer the extent of duration
the larger the total dose per unit delivery system needs to be. Hence
there is a limitation to the amount of drug that can be practically
incorporated into such a system.
4)Molecular weight or size Small molecules may pass through pores of a
membrane by convective transport. This applies to both, the drug release
from the dosage form and the transport across a biologic membrane. For
biologic membranes the limit may be a molecular weight of 150 and 400
respectively for spherical molecules and chain like compounds respectively.
5)Solubility For all mechanisms of absorption the drug must be present at the
site of absorption in the form of solution. During the Preformulation study it
is necessary to determine the solubility of the drug at various pH values. If
the solubility is less than 0.1 μg/ml (in acidic medium) one may expect
variable and reduced bioavailability. If the solubility is less than 0.01 μg/ml
absorption and availability most likely become dissolution limited
dissolution limited. Hence driving force for diffusion may be inadequate. It
seems that drugs are well absorbed by passive diffusion from the small
intestine upon per oral administration if at least 0.1 to 1% is non ionised
form.
Classification of oral sustained and controlled drug
delivery system

SR/CR

DELAYED TRANSIT AND DELAYED

CONTINUOUS RELEASE
CONTINUOUS RELEASE
RELEASE SYSTEM SYSTEM
SYSTEM
Control release dosage form Release Formulation Designs
These systems release the drug continuously for prolonged period of time
along the entire length of GIT with normal transit time .
1. Dissolution controlled release system
2. Diffusion controlled release system
3. Dissolution and diffusion
4. Ion exchange resin complex
5. Ph-dependent formulation
6. Osmotic pressure controlled release system
7. Hydrodynamic pressure controlled release system
Characteristics That may Make A Drug Unsuitable For Control
release Dosage Form
1) Short elimination half-life
2) Long elimination half-life
3) Narrow therapeutic index
4) Poor absorption
5) Active absorption
6) Low or slow absorption
7) Extensive first pass effect
a) Intestinal release system :A drug may be enteric coated
for intestinal release for Several known reason to
prevent gastric irritation, destabilization in gastric pH.
b) Colonic release system :Drug are poorly absorbed
through colon but may be delivered to such a site for two
reason-
1. Local action as in the treatment of ulcerative colitis
2. Systemic absorption of protein and peptide drug like
insulin and vasopressin.