3. INTRODUCTION:
Definition: Depot is a formulation which is aqueous or
oleaginous suspension (or) oleaginous solution administered
by parental route i.e. by sub-cutaneous or intra muscular.
Depot is a drug reservoir that releases the drug molecule
continuously at a rate determined to a large extent leading
to prolong absorption of drug molecule from formulation
The ingredient used for depot formulation should be sterile,
pyrogen free, non-irritating, bio-compatible, bio-
degradable and non toxic compounds
08-02-20163
4. Improved patient convenience and compliance
Prolonged steady state drug plasma concentration
Maximum utilization of drug
Less frequency of dosing
Reduction in health care cost through improved therapy
ADVANTAGES:
08-02-20164
5. Decreased systemic availability
Poor invitro- invivo co-relation
Possibility of dose dumping
Retrieval of drug is difficult in case of toxicity,
poisoning or hypersensitivity reactions
Reduced potential for dosage adjustments
Higher cost of formulations
DISADVANTAGES:
08-02-20165
6. APPROACHES:
1) Use of viscous, water-miscible vehicles, such as aqueous
solution of gelatin or polyvinylpyrrolidone.
changes in solubility of drug
changes in time release once drug is administered
changes in state of drug post administration
2)Utilization of water-immiscible vehicles such as
vegetable oils, water repelling agents such as aluminium
monostearate
08-02-2016
6
7. 3)Formation of thixotropic suspensions
structural break point
change in flow properties
change in dissolution characteristics
4)Preparation of water insoluble drug derivatives such as
salts, complexes and esters.
chemical modification without affecting
therapeutic activity
kinetics were influenced
stability enhanced
08-02-2016
7
8. 5)Dispersion in polymeric microspheres or microcapsules
such as lactide-glycolide homopolymers or copolymers
use of surface active agent
polymerization insitu or through reaction
microcapsule using various techniques
6)Co-administration of vasoconstrictors
08-02-2016
8
9. TYPES OF DEPOT PREPARATIONS:
Depot formulation may be classified on the
basis of the process used for controlled drug
release as follows:
A)Dissolution-controlled depot formulation
B)Adsorption-type depot formulation
C)Encapsulation-type depot formulation
D)Esterification-type depot formulation
08-02-2016
9
10. DISSOLUTION-CONTROLLED
DEPOT FORMULATIONS:
The rate of dissolution is controlled by slow dissolution of
the drug particle in the formulation or tissue fluid
surrounding the formulation
The rate of dissolution can be determined mathematically as
Q/t = SDC/ h
Q/t = rate of dissolution
S = surface area of drug particle
D = diffusion coefficient
C = saturation solubility
H = thickness of hydrodynamic diffusion layer
1008-02-2016
11. Two approaches to control dissolution are:
a) Formation of salt or complexes with low aqueous
solubility:
A water soluble basic or acid drug can be
rendered effective as a depot by transforming it into a salt
with an extremely low aqueous solubility.
EX: Aqueous suspensions of benzathine pencillin G
(c=2mg/ml) and procaine pencillin G (c=4mg/ml) from
water soluble alkali salts of acidic pencillin G.
08-02-2016 11
12. b) Suspension of macro crystals: Large crystals
are known to dissolve more slowly than small
crystals. It is called the macro crystal principle and
can be applied to control the rate of drug
dissolution
EX: aqueous suspension of testosterone isobutyrate
for I.M injection
08-02-2016 12
13. Suspension of macro crystals is having exception in case of
Pencillin G procaine suspension in gelled peanut oil for
I.M injection. This is due to possibility that micronized particles
may reach the interface of tissue fluid and gelled suspension at a
significantly slower rate than the larger particles.
Drawbacks:
Release of drug molecules is not of zero order kinetics as
expected from the theoretical model
Surface area of drug particles diminishes with time
The saturation solubility of the drug at the injection site cannot
be easily maintained.
08-02-2016 13
14. ADSORPTION-TYPE OF DEPOT
PREPARATIONS:
This depot preparation is formed by the binding of drug
molecules to adsorbents.
In this case only the unbound, free species of the drug is
available for absorption.
The equilibrium concentration of free, unbound drug
species (C)f is determined by the Langmuir relationship,
(C)f/(C)b = 1/a(C)b,m+(C)f/(C)b,m
EX: Vaccine preparations in which antigens are bound to
highly dispersed aluminium hydroxide gel to sustain their
release.
08-02-2016 14
15. ENCAPSULATION-TYPE DEPOT
PREPARATIONS:
This type of depot formulation is prepared by encapsulating
drug solids within a permeation barrier or dispersing drug
particles in a diffusion matrix
Both of these are made from either bio-degradable or bio-
absorbable polymers. such as gelatin, dextran, polyactate ..etc..
Release of drug is controlled by
rate of penetration across the diffusion barrier
rate of biodegradation of barrier macro molecules.
1508-02-2016
17. ESTERIFICATION-TYPE DEPOT
PREPARATIONS
This depot preparation is produced by synthesizing the bio-
convertibles esters of a drug and then making up an injectable
formulation.
This formulation forms a drug reservoir at the site of injection.
Rate of absorption is controlled by
interfacial partitioning of drug esters from reservoir to
tissue fluid.
rate of bioconversion of drug esters to regenerate active
drug molecules.
EX: Fluphenazine enanthane,testosterone17β cypionate in
oleaginous solution
08-02-2016 17
19. LONG ACTING VIT-B12
PREPARATION:
08-02-2016 19
Reasons for preparation of long acting
vitB-12 preparation:
VitB-12 which was given by the oral route
is mediated by gastric intrinsic factor of castle
which is secreted by the gastric parietal cells
This gastric intrinsic factor is easily saturated by
vitB-12 and forms vitB12-intrinsic factor
complex.
20. Attachment of vitB12-intrinsic factor complex to receptors
on the ileal surface requires calcium and a ph>6.
After a delay of several hours at or with in ileal mucosa,
the vitamin is transported by the blood stream to the liver
and other organs
It is responsible for over whelming majority of the
megaloblastic anemias
08-02-2016 20
21. VitaminB-12 is rapidly and quantitatively absorbed from
intramuscular and subcutaneous sites of injection
The plasma level of vitamin B12 reaches its peak concentration
within 1hr of intramuscular injection
VitB12 which was given by these routes is the medication of
choice for the treatment of pernicious anemia
The usual maintenance treatment of patients with pernicious
anemia is by monthly injections of vitamin B12(0.03-1.0mg)
Unfortunately, much of the injected doses were lost through
urine
Different approaches were developed for formulation of
vitaminB12
08-02-2016 21
22. First approach to the development of a parental controlled
vitaminB12:
VitaminB12 in a concentrated partially hydrogenated gelatin
(32%) solution.
Drawback: No sustained release behaviour was obtained on
human testing
Second approach to the development of a parental controlled
vitaminB12:
Crystalline vitaminB12 was suspended in seasame oil gelled
with aluminium monostearate (2%)
Drawback: Urinary excretion of this vitamin was unacceptable
08-02-2016 22
23. 08-02-2016 23
Third approach to the development of a parental controlled
vitaminB12:
VitaminB12-zinc-tannate complex was prepared and
suspended in sesame oil gelled with aluminium monostearate
(2%).
This preparation achieved a significant prolongation of the
absorption of vitB12 when compared to former two
approaches
Urinary loss was significantly reduced.
24. MARKETED PRODUCT:
Depinar(armour pharma) which consists of combination
of readily absorbable vit-B12 and sustained release vit-
B12 with zn-tannate.
Adequate maintenance therapy has been provided when
given at a dose of 1mg/ml at interval of 8-12 weeks.
08-02-2016 24
25. LONG ACTING ANTIPSYCHOTIC
PREPARATIONS:
Phenothiazines were the most prescribed antipsychotic
drugs
Fluphenazine, is the most potent derivative of
phenothiazines due to its potency, prolonged duration of
action.
Prolongation of the antipsychotic activity of fluphenazine
can be accomplished by esterification
EX: Fluphenazine decanoate, fluphenazine enanthate
Esterification of fluphenazine with enanthate moiety
prolongs its activity
08-02-2016 25
26. Parental(IM or SC) administration of either ester in sesame oil
produces anti-psychotic action for an average duration of 2
weeks
Onset of action generally takes 24-72 hrs and effect on
psychotic symptoms becomes significant within 48-96hr.
08-02-2016 26
27. Long acting antibiotic preparations:
Aqueous solubility of penicillin is reduced by converting
penicillin to penicillin G procaine (aq. solubility 4mg/ml)
EX: Duracillin
Long acting insulin preparations:
plasmat1/2 of insulin = 40min
insulin-protamine complex has isoelectric point at pH 7.3 and
therefore it is insoluble in body fluid which shows sustained
release upto 24hrs,stability issues arises but solved by adding
zinc chloride.
08-02-2016 27
28. Long acting adrenocorticotropic hormone preparations:
When given parentally ACTH gets disappeared due to its
shorter t1/2 i.e.; 15min. By the addition of partially hydrolysed
gelatin solution into injectable ACTH solution shows prolonged
release. Gelatin inhibits protein binding of ACTH and enhances
response.
Long acting anti-narcotic preparations:
Gelled oleaginous suspension of narcotic antagonist – salt
complex shows sustained release for 72hrs
Long acting contraceptive preparations:
Norethindrone in a biodegradable polymer beads
Norgestrel 17β-fatty acid esters in oleaginous solution.
08-02-2016 28
30. POLYMERS USED…….
Generally Biodegradable polymers are used because as
they gets degraded in the body
NATURAL: Albumin, starch, dextran, gelatin, fibrinogen,
haemoglobin.
SYNTHETIC: Poly ethyl-poly alkyl cyanoacrylates, poly
amides, poly acryl amides, poly amino acids, poly
urethane.
08-02-2016 30
31. PROPERTIES:
Depot systems should have the following properties
It should be safe from accidental release
It should be simple to administer and remove
It should be inert and biocompatible
It should be capable of achieving high drug loading
It should be easy to fabricate and sterilize
It should be free of leachable impurities
08-02-2016 31
32. CONCLUSION:
Depot preparations or parental controlled drug delivery
system is designed to achieve a desired pharmacological
response in a sustained manner at a selected site without
undesirable interactions at the other sites.
Extended release parental products are complex dosage
forms, requiring careful development of test methods and
acceptable criteria for the specifications.
08-02-2016
32
33. REFERENCES:
Chien Y.W., Novel drug delivery systems; Drugs
and pharmaceutical sciences(2nded,vol-50).
Lachman L.& Lieberman H. & kanig J
www.wikipedia.org
www.pharmatutor.org/articles/review-parental
controlled drug delivery systems.
08-02-2016
33
