Parenterals are sterile preparations that are injected through the skin or mucous membranes into the body. They provide quick onset of action and accurate dosing but require aseptic technique. Common routes include intramuscular, intravenous, and subcutaneous. Advantages include rapid absorption but disadvantages include pain and risk of infection. The only approved treatment for spinal muscular atrophy (SMA) is the drug Spinraza, which works by binding to mRNA to make the SMN protein functional and treat SMA, an inherited neuromuscular disease. Future parenteral delivery systems aim to reduce injections and provide sustained drug release through methods like nanoparticles, in-situ forming depots, niosomes, and liposomes.

1. PARENTERALS
PRESENTEDBY-ANKUSHDUBEY

2. .The term parenteral is derived from two
Greek words:- 1.Para(outside)
2.Enteron(intestine)
.These are the sterile , pyrogen free
preparations which are injected through
skin or mucous membrane into the
internal body compartments.

3. ADVANTAGES
1.Quick onset of action.
2.Accurate dose administration.
3.Can be employed when oral route is not
compatible.
4.Minimise first pass effect.
5.More bioavailability.

4. DISADVANTAGES
1. Must be administered aseptically so
extra precautions are required.
2. Pain at site of injection.
3. Administration of drug through wrong
route may provide fatal effect.eg:-IM
injection if administered via IV route may
cause blockage of blood vessel.
4. Self administration is difficult.

5. ROUTES OF ADMINISTRATION
ROUTE DRUG
1. Intra-muscular Influenza vaccine
2. Intra-dermal Local anesthetic
3. Intra-venous Cis-platin
4. Sub-cutaneous Insulin
5. Intra-articular Corticosteroids
6. Intra-synovial Bursa injection.
7. Intra-spinal Lidocaine

6. 8. Intra-thecal Methotrexate
9. Intra-arterial Temazepam
10. Intra-cardiac Epinephrine
11. Intra-cisternal Bupivacaine
12. Intra-peritoneal Chemotherapy
13. Intra-pleural Anti-coagulants

7. TYPES OF PARENTERALS
1.Powder for injection:- eg.- cefuroxime for injection.
2.Colloidal solution:- eg.- iron dextran injection.
3.Injectable emulsion:- eg.- propofol USP.
4.Injectable suspensions:- eg.- methylpredinisolone acetate
injection.
5.Oily injection:- eg.- Dimercaprol injection.
6.Infusion fluids:- eg.- NaCl+ Glucose infusion.

9. PRE-FORMULATION FACTORS
1. pH.
2. Solubility.
3. Dissociation constant.
4. Tonicity.
5. Compatibility of API with solvent.
6. Oxidation and reduction potentials.
7. Particle size.

10. INGREDIANTS OF PRENTERALS
1. Solute(API).
2. Added substances(excipients):-
a. Anti-microbial agents.
b. Buffers.
c. Anti-oxidants.
d. Tonicity agents.

11. e. cryoprotective agents.
f. suspending agents.
g. emulsifying agents.
h. vehicle- 1.Aqueous.
2.Oily.
3.Alcohols.

12. GENERAL PROCEDURE
FOR PREPARATION
STEPS:-
1. Cleaning and washing of closures and containers.
2. Preparation of solution.
3. Sterilization of solution.
4. Filling.
5. Sealing.
6. Final sterilization.
7. Packing.

14. CONTAINERS AND CLOSURES
1. Glass.
2. Plastic.
a. Ampoules(single dose)
b. Vials(multiple doses)
3. Rubber closures with Al-caps.

15. EVALUATION TEST FOR
PARENTERALS
1.Test for pyrogens:- a. Sham test
b. Lal test
2. Sterility testing.
3. Clarity test.
4. Leaker test.

16. Q. Why only parenteral are used for
immunization/vaccination not
any other dosage form?
A. Pathogens(killed or attenuated) are used for immunity
development. When give as tablets, capsules, suspensions
or emulsions they are not stable and will not be able to
interact
with T&B lymphocytes in blood to generate immune
response for anti body production.
While in case of parenterals the antigens
directly reach blood and generate a quick immune

17. SMA:-An orphan disease
.Orphan diseases are those which are very rare and
occurs in about 200,000 people all
over globe.
.SMA-.Spinal muscular atrophy.
.Inherited neuromuscular disease.
.It is an autosomal recessive
neuromuscular disease characterized
by degeneration of the motor neurons

18. in the anterior horn of spinal cord.
resulting in atrophy of the muscles
in limbs and trunk.
Cause:-Due to decreased levels of
SMN(survival motor neuron)
protein and it is due to
homozygous deletion of
7th base pair in SMN1 gene.
.Lack of SMN protein cause death of
motor neurons.

19. . SMA is one of the major genetic cause of
infant mortality.
. Infants with SMA die within 18 months
after birth.
. Individuals with SMA can become paralyzed
and face difficulty in performing the basic
functions of life like breathing and swallowing.

21. SPINRAZA-Only drug for
SMA treatment on globe
.Spinraza was developed by collaboration of Biogen
and Ionis.
.It was approved by FDA for SMA treatment on
December 23rd ,2016.
.It is called as orphan drug.

22. Concentration- 2.4 mg/ml.
Trade name- Spinraza
Non-proprietary name- Nusinersn
Chemical nature- 2’-o-
methylphosphorothioate
oligoribonucleotide.
Salt name- Nusinersn sodium.
Manufacturer:- Biogen.
Metabolism:- By 3’-5’-exonuclease within
nucleus.

23. Elimination route:-Urine.
Use:- To treat spinal muscular atrophy (SMA).
Dose:- 1.Loading dose:-On day 1,15,29, 64th in first year of
treatment.
2.Maintenance dose:-Every 4th month next year
onwards.Route:-Intrathecal.
Price:-First year treatment cost- 5 crores and next year onwards the
treatment cost is 2.6 crores.
.Spinraza is an orphan drug which is used to terat SMA which is an
orphan disease.
.It provide complete cure of SMA and only one side effect of it is seen in
clinical trials

24. MECHANISM OF ACTION
SMN PROTEIN:-.Important for survival and
development of motor
neurons.
.Produced by SMN1 and SMN2
gene.
.SMN1 gene produces SMN protein in large amount
while SMN2 gene produces SMN protein in very less
amount.

25. .In SMA patients SMN1 gene is affected and
production of SMN protein is very less as only by
SMN2 gene.
.As in SMA patients,7th base pair on mRNA from
SMN1 gene is deleted and this lead to decreased
production of SMN protein.
.Role of spinraza:- It is a short RNA sequence that
binds on 7th exon position of mRNA and make it
functional.

27. FUTURE OF PARENTERALS
. Drug delivery technologies that can reduce
the total no. of injections throughout the drug
therapy period will be truly advantageous not
only in terms of patient compliance but also to
improve the quality of therapy.
. A number of advancement have been made in
the area of parenteral drug delivery that can
allow drug targeting and the sustained.

28. drug release.
1. Solid lipid nanoparticles:-It consist of
encapsulated lipophilic drug
into oil droplets.
Advantages- 1.Sustained release of drug.
2.Prevent photochemical and oxidative
degradation of drug.
Disadvantage- Low viscosity.
Use- 1. Cancer treatment.
2. CVS diseases.
3. Rheumatoid arthritis treatment.

29. 2.In-situ forming parenteral drug delivery system:- It
can replace microspheres and implants as parenteral
depot systems.
Advantages- .Ease of administration
.Less stressful manufacturing condition
sensitive drugs.
.Cost effective.
Eg. -Thermoplastic pastes-
.These are semi-solid polymers can be injected
melted and form a depot on cooling to body
and provide sustained release of drug present in their

31. 3.Niosomes:-These are non-ionic
surfactant vehicles obtained on hydration
synthetic non-ionic surfactants of the alkyl
di-alkyl polyglycerol ether class with or
without incorporation of cholesterol or
lipids.
Eg. - Vassopresin,estradiol.
Advantages- .Osmotically active and
stable.

32. . Can accommodate drug with wide range
of solubilities.
. Sustained release of drug.
. Improved bioavailability of drug.

33. 4.Liposomes:-.Made up of phospholipid. .The
amphiphilic phospholipid molecules form a
bilayer sphere in an attempt to shield their
hydrophobic groups from aqueous environment
while still maintaining contact with the aqueous
phase via hydrophilic head groups.
Uses-.Anti-cancer drugs.

34. Advantages-1.Rapidly cleared from body
as largely taken up by liver macrophages,
this can minimize side effects of anti-
drugs.
2. Liposomal vaccines can be stored at
refrigeration temperature for upto 12
months without any loss in activity.
3. Reduces risk of renal toxicity in case of
anti-fungal drugs.

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