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Transcript of parenteral suspensions
OF PARENTERAL SUSPENSION Factors affecting in design of parenteral suspension 1)the particle size distribution of the drug to be suspended
2)viscosity inducing agents,
3) use the right drug polymorph
4) solvent form
5 ) conduct meaningful temperature cycling
studies to evaluate the rate and the extent of temperature
effects on physical as well as chemical stability of suspension. Advantages Disadvantages 1-It is better for the therapeutic use of drugs that are insoluble in convention solvents.
2-In this dosage form there is increased resistance to hydrolysis
& oxidation as drug is present in the solid from.
3-Formulation of controlled released drug is possible in this dosage form.
4-There is elimination of hepatic first pass effect. Difficulty in formulation: Parenteral suspensions limit the formulator in selecting the ingredients, which are parenterally acceptable as suspending agent, viscosity inducing agent, wetting agent, stabilizers and preservative.
Difficulty in manufacturing: Special facilities are required to maintain aseptic condition for manufacturing processes such as : crystallization, particle size reduction, wetting, sterilization.
The stabilization of suspensions for the period between manufacture & use present a number of problems. e.g. solids gradually settle & may cake, causing difficulty in redispersion prior to use.
Maintenance of physical stability is very difficult in this dosage
There may be chances of nonuniformity of dose at the time of
administration. Maintain sterility during storage & use .
It should be easily drawn into a syringe (Syringeability) and readily ejected from the syringe (Injectability).
Re‐ suspension of drug particles should occur easily with mild shaking .
The dispersed particles do not settle rapidly after shaking . Ideal characteristics of parenteral suspension Particle size should be small & uniform.
Cake formation shouldn’t occur during its shelf life.
The suspensions should maintain its stability and elegance during its shelf life.
It should be isotonic & non‐irritating . Cont. The drugs, which are insoluble and are difficult to be formulated as solution .
For the drug which are more stable when suspended than in solution form . Why Parenteral suspensions ? Important Properties of the parental suspension for the
formulation development Typical excipients used in parenteral suspensions METHODS FOR PREPAPARATION OF PARENTERAL
SUSPENSION Aseptically combining
sterile powder and vehicle. In situ crystal formation by combining
sterile solutions. Formulation parameters of parenteral suspension : Other Forces Zeta potential 1 - Interfacial properties Deflocculated Suspention But in case of High-concentration Drugs
Ex :Procaine Penicillin G Small-concentration Drugs Flocculation and Deflocculation Flocculating agents:
Polymers What about Small concentration Drugs ?? Flocculation and Deflocculation Flocculation and Deflocculation Examples Interfacial properties
Flocculation and Deflocculation
Crystal Growth Deflocculated suspension Flocculated suspensions Thank you Stability study & evaluation Syringeability Injectability Clogging Drainage Resuspendibility Sedimentation Volume Freeze‐Thaw cycles Crystal Growth in susp. ParticleSizeMeasurements Zeta Potential determinations Compatibility with diluents Viscosity Structured vehicles Shipping &
Product‐PackageInteractions Vaccines Insulin Zinc suspension Betamethasone Sodium Phosphate Dexamethasone acetate Deca dron ®
Methylprednisilone acetate Depo Medrol® Sterile ampicillin suspension Sterile Aurothioglucose suspension E.g. Cholera vaccine ,
Tetanus toxoid adsorbed - Aq. Suspension Extended acting insulin preparations are microcrystalline
suspensions that provide their protracted effects by slow dissolution
of the crystals and gradual release of insulin into the blood stream avoiding hypoglycemia Brand name :Celestor®
Anti histaminic , anti inflammatory USES: This medication is used to treat various conditions such as severe allergic reactions, arthritis, blood diseases, breathing problems, certain cancers, eye diseases, intestinal disorders, and skin diseases. dispense as powder which
is to be reconstituted at time of administration vegetable oil suspension
Generic name: aurothioglucose
brand name: Solganal Aurothioglucose is a gold-containing chemical (salt) used for treating rheumatoid arthritis. Procaine penicillin G suspension Penicillin in the form of aqueous soluble sodium or potassium salt rapidly absorbed from subcutaneous & intramuscular. Due to rapid absorption high peak level of penicillin was achieved. Then its concentration is decline rapidly in mater of few hours due to the rapid urinary excretion of penicillin.So pharmaceutical technices was done and discover that using penicillin G as parantral suspension for intramusclar give long acting penicillin+
penicillin under the control of dissolution of penicillin G procaine in the tissue fluid The drug nanocrystals do not belong to the future; the first products are already on the market Nanoparticals as parentral suspension for IV administration eg.
clofazimine nanosuspension for intravenous used for treatment of leprosy , treatment of Mycobacterium avium complex infections in patients in AIDS. Solubility of drug in biological fluids at the injection site.
#Lipid solubility and oil water partition coefficient of the drug.
# Pka of the drug.
# Dissolution rate of the solid drug from its dosage from
#pH of the vehicle & tonicity of suspension.
#Particle size of the drug in suspension.
#Compatibility of other ingredients in the dosage from. Flocculating \ suspending agents uses a flocculating agents(s) to from loosely bound aggregate or flocs in a controlled manner that settles rapidly but redisperses easily upon agitation used to keep the dispersed particles in the suspension in a deflocculated state
These agents function as viscosity imparting agent & reduce the rate of sedimentation of the dispersed particles viscosity building agents Electrolytes, surfactant and hydrophilic colloids have been typically used as flocculating agents. wetting agents Wetting of the suspended ingredient(s) is one of the most important aspects of the injectable suspension because of the hydrophilic powders often suspended in aqueous systems
E.g :gelatin , carmelase Tonicity Agents Isotonicity of the parenteral preparation for subcutaneous or intramuscular administration is desired to prevent pain; irritation and tissue damage at the site of administration
the aqueous solution of tonicity agents used in parenteral suspensions include dextrose & various electrolytes Preservatives Antimicrobial agents are required for parenteral products that are intended for multiple dosing, in order to protect the product from accidental microbial contamination during clinical usage & maintain sterility
Similarly, preservatives should be added to formulations aseptically packaged in signal dose vials if the active ingredient(s) does not have bactericidal or bacteriostatic properties or is growth promoting. Antioxidants Antioxidants are added in the formulation to minimize this degradation by preferentially undergoing oxidation as the result of their lower oxidation potential or by terminating the propagation step in the free redical oxidation mechanism
Antioxidants are either used alone or in combination with a chelating agent or other antioxidants
Certain compounds (ascorbic acid of citric acid) have been found to act as synergists & increase the effectiveness of antioxidants that block oxidative reaction Chelating agents Chelating agents sequester heavy metals, thereby preventing the catalysis of oxidation reaction
E.g: EDTA The inability to resuspend drug particles upon caking usually
result from particles setting as a hardened sediment call a
“cake” it will occur when attractive forces among drug particle
are greater than forces between solids particles and the
Crystal growth and extremes in flocculated deflocculated
suspension can lead to caking
Deflocculated system will settle slowly as
individual particles which will become closely packed
Thus complete dispersion of small narrow ranged
particles with appropriate amount of wetting agent and
increasing zeta potential will minimize the tendency
of these particles to agglomerate and form a hard cake.