FORMULATIO
N OF CR/SR
DOSAGE
FORMS
Presented by- Kunal S. Deshmukh
M. Pharm 1st
year ..............((Department of
Pharmaceutics)
Guidance by- Dr. M.A. Channawar
Professor
(Department of Pharmaceutics)
P. Wadhwani College Of Pharmacy,
Yavatmal
INDEX
Introduction
Physicochemical Properties
Biological Properties
Summary
INTRODUCTION
Sustained Release
It includes any drug delivery system that
achieves slow release of drugs over an extended
period of time not particularly at a pre-determined
rate.
Controlled Release
It includes any drug delivery system from which
the drug is delivered at a predetermined rate over
a long period.
PHYSICOCHEMICAL
PROPERTIES
Aqueous Solubility
Partition coefficient (P-value)
Drug Pka
Drug stability
Molecular size & Molecular weight
Protein Binding
1) AQUEOUS SOLUBILITY
Most of the active pharmaceutical moiety (API)
are weakly acidic or basic in nature that affect
the water solubility of API.
Weak water soluble drugs are difficult to
design the controlled release formulations.
High aqueous solubility drug show burst
release followed by a rapid increment in plasma
drug concentration. These types of drugs are a
good candidate for CRDDS.
BCS class-III & IV drugs are not a suitable
candidate for this type of formulations.
2) PARTITION COEFFICIENT
(P-VALUE)
P-value denotes the fraction of the drug
into oil & aqueous phase that is a
significant factor that affects the passive
diffusion of the drug across the biological
membrane.
High P value of compound are predominantly
lipid soluble and have very low aqueous
solubility and thus these compound persist
in the body for longer period.
The drugs are having high or low P value not
suitable for CR, it should be appropriate to
dissolve in both phases.
3) DRUG PKA
PKa is the factor that determined the
ionization of drug at physiological pH in GIT.
Generally, the high ionized drugs are poor
candidates for CRDDS.
The absorption of the unionized drug occurs
rapidly as compared to ionized drugs from
the biological membranes.
The pKa range for an acidic drug that
ionization depends on the pH is 3.0 to 7.5
and for a basic drug it lay between 7 and 11.
4) DRUG STABILITY
Drugs that are stable in acid/base, enzymatic
degradation, and other gastric fluids are good
candidates for CRDDS. If drug degraded in the
stomach and small intestine, it not suitable for
controlled release formulations because it will
decrease in bioavailability of concern drug.
5)Molecular size &
molecular weight
The molecular size & molecular weight are two
important factors which affect the molecular
diffusibility across a biological membrane. The
molecular size less than 400D is easily diffuse
but greater than 400D create a problem in drug
diffusion.
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 the protein binding increases the
biological half-life. So there is no need to
sustain the drug release.
BIOLOGICAL FACTORS
Absorption
Biological half-life(t1/2)
Dose size
Therapeutic window
Absorption window
Patient physiology
1) ABSORPTION
Uniformity in rate and extent of absorption is
an important factor in formulating the
CRDDS. However, the rate limiting step is
drugged release from the dosage form.
The absorption rate should rapid then release
rate to prevent the dose dumping. The
various factors like aqueous solubility, log P,
acid hydrolysis, which affect the absorption
of drugs.
2) BIOLOGICAL HALF-LIFE
(T1/2):
In general the drug is having short half-life
required frequent dosing and suitable
candidate for controlled release system. A
drug with long half-life required dosing after
a long time interval.
Ideally, the drugs having t1/2 2-3 hrs are a
suitable candidate for CRDDS. Drugs have
t1/2 more than 7-8 hrs not used for
controlled release system.
3) DOSE SIZE
The CRDDS formulated to eliminate the
repetitive dosing, so it must contain the large
dose than conventional dosage form. But the
dose used in conventional dosage form give
an indication of the dose to be used in
CRDDS.
The volume of sustained dose should be as
large as it comes under acceptance criteria.
4) THERAPEUTIC WINDOW
The drugs with narrow therapeutic index are
not suitable for CRDDS. If the delivery
system failed to control release, it would
cause dose dumping and ultimate toxicity
5) Absorption Window
The drugs which show absorption from the
specific segment in GIT, are a poor
candidate for CRDDS. Drugs which
absorbed throughout the GIT are good
candidates for controlled release
6) PATIENT PHYSIOLOGY
The Physiological condition of the patient like
gastric emptying rate, residential time, and
GI diseases influence the release of the drug
from the dosage form directly or indirectly.
SUMMARY
