gives idea about the injectable bio pharmaceutics. methods of preparation use test containers

1. BIOPHARMACEUTICS OF INJECTABLES
Arantha. J. Joseph
1st Year M.Pharm
Dept.Of Pharmaceutics

2. Introduction
• Biopharmaceutics
• An injection Drug directly into the blood stream.
[bypassing physicochemical and physiological influences.]
• Depending on the type of formulation
▫ varying degrees of a depot are established.
▫ Eventual drug absorption is influenced by several physicochemical and
physiological factors.
• Considerations passive diffusion and blood flow.
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3. A . Physicochemical factors affecting drug absorption by
injection:
• No absorption step drug is administered directly into the
blood stream.
• Extra vascular injection require an absorption.
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4. Drug solubility
• Major criterion for absorption.
• Drugs remain in solution at the injection site.
• Diff. In PH
Passive diffusion
• Drug in solution passes from the extra vascular to the intravascular
tissue fluids by passive diffusion.
▫ Affected by physiological factors
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5.  Conc. Gradient :
The rate at which a drug mole. crosses a semi permeable membrane by
passive diffusion
• Described by Fick’s first law,
dq/dt=DA(C1-C2)/l
dq/dt rate of drug diffusion.
D Diffusion coefficient of the drug through membrane.
A surface area
C1=conc. of diffusing substance in extracellular fluid.
C2=conc. of diffusate in the intracellular fluid.
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6. Partition coefficient
• Immiscible solvents
• The distribution of a solute b/w an aqueous
environment and a lipid membrane
PC=k=Ca/Cb
• High partition coefficient will pass readily from the aqueous phase into the
membrane.
• Exhibit a higher rate of diffusion.
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7. Ionization
• Ionization has effect on drug
▫ absorption distribution and excretion.
The degree of ionization is determined by the ionization constant.
HA+H2O H3O+A-
Equilibrium constant
Keq= [H3O+][A-]/[HA][H2O]
• Since the molar conc. of H2O is much larger than any of the other values and
remains constant
Keq[H2O]=Kion=[H3O]+[A]/[HA]
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8. So ,
pH=Pka+log[A-]/[HA]
Binding to macromolecule
• Biological fluids contain macromolecule
▫ such as protein which may have affinity for certain drugs.
Drug + Macromolecule Drug-Macromolecule
complex
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9. Osmolality
• A solution is isoosmotic with tissue fluid when the total no. of
dissolved particle in the two systems are equal.
• Injectable products are formulated to be isoosmotic to reduce the
possibility of irritation.
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10. Differences In Physical Form Of Medication
• Aqueous Solution
• Aqueous Suspension
• Oleaginous Solution
• O/W Emulsion
• W/O Emulsion
• Oleaginous Suspension
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Fastest release
Slowest release

11. 1.Aqueous suspension:
• The rate determining step is its dissolution in tissue fluid.
Rate of dissolution KS=(Cs-Ct)
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drug drug drug
Solid fine
particle
dissolution
Dissolved in
tissue fluids
diffusion
partitioning
absorbed

12. 2.Oleaginous solution
The major factor involved in release from this dosage
form is partitioning from the oil phase to tissue fluid.
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drug drug drug
Dissolved in oil
partitioning
Dissolved in
tissue fluids
diffusion
partitioning
Absorbed

13. 3.Emulsion
a)Oil in water emulsion:
Drugs are generally dissolved in the dispersed oil phase to establish a
prolonged release profile.
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drug drug
drugdrug
Dissolved in oil phase
Partitioning
Drug dissolved in
aqueous phase
Diffusion
mixing dilution
Dissolved in tissue fluids
Diffusion
partitioning
Absorbed

14. b)Water in oil emulsion
The partitioning of drug from the aqueous phase to the external oil
phase and then to the surrounding tissue fluid will lead to a prolonged
release profile.
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Drug Drug
DrugDrug
Dissolved in aqueous
phase
Partitioning
Dissolved in oil
phase Partitioning
into tissue
fluids
Dissolved in tissue
fluids
Diffusion partitioning
Absorbed

15. 4.Oleaginous suspension
• Normally administered IM.
• The rate determining step is drug dissolution either into the oil
phase or directly into tissue fluids depends on its relative solubility.
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16. 16
Drug
Suspended in oil
Drug
Dissolved in oil
Drug
Dissolved in
tissue fluid
Drug
Absorbed
Dissolution
Partitioning into tissue
fluid
Partitioning
in tissue
fluid
Diffusion partitioning

17. B. Physiological factors affecting drug absorption by
injection
1.The intravenous route
No absorption step is necessary. so there is no physiological factors are
affecting.
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Distance in body Circulation time(sec)
Arm-ear 8-14
Lung-ear 3-5
Arm-finger 17.5±4.4
Arm-toe 24.8±4.4
Right ventricle-left ventricle 2-4

18. 2.The Extra vascular route
• The major physiological factors affecting passive diffusion through
capillary cell membrane and blood flow are:
▫ Anatomical site
▫ Muscle movements
▫ Tissue condition of health
▫ Body temperature
▫ Patient age
▫ General distance state
▫ Presence of mediators.
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19. 1)Anatomical site
• The greater the no of capillaries at the site , the larger will be the
surface area available for absorption , so more absorption occurs.
Eg: rate of onset of tachycardia as measured by elevation in pulse rate,
demonstrated by injecting a solution of atropine into diff. anatomical
region
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Onset of action
tachycardia(min.)
IV <5
Broad ligament 5-10
Subcutaneous 40
Intramuscular 40

20. 2.Muscle movement
• The rate of flow through lymphatic vessels is increased greatly with
increasing muscle movement.
Eg: Rabbits injected with Black Tiger Snake venom, it take up to
8hrs for the venom to cause death in rabbits with immobilized
limbs, where as other died 2.5 hrs.
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21. 3.Tissue condition
• Changes in tissue vascularity caused by scarring will affect drug
absorption.
• Injection into insulin wheals causes absorption to be delayed and
efficacy reduced.
4.Body temperature
• Rate of drug absorption changes in direct proportion to body
temperature.
• Rate of metabolism and most other physical and chemical reactions.
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22. Eg: in general colder external temperature cause peripheral
vasoconstriction
• warmer temperature cause peripheral vasodilation.
5.Patient age.
• Reduced adipose tissue .
▫ Reduced adipose tissue results in a greater availability of drug to the
systemic circulation
 since the retention of drug by such tissue is reduced.
 They have high partition co-efficient.
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23. 6.Disease state
• Absorption at the intramuscular injection site of an aqueous
suspension of penicillin G seemed to be reduced in patients who
suffered heart failure.
7.Presence of mediator enzymes.
• The enzyme hyaluronidase is known to increase the onset of drug
absorption when given together with an intramuscular injection.
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24. Example of biopharmaceutic principles
INSULIN
• The rate of SC absorption is reported to be highly variable within
and among subjects.
• Influenced by numerous factors such as
▫ Ionic equilibrium.
▫ Temperature of the product
▫ Site of injection
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25. Ionic equilibria
• Soluble insulin either admixed with soluble insulin diluting medium
or Lente diluting medium was injected simultaneously by sc.
• The incremental insulin levels observed when administration of
soluble insulin admixed with its own medium.
▫ The separate simultaneous administration of soluble and Lente insulin
results higher insulin levels when compared to the admixture injection
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26. ▫ When soluble and Lente human insulin are admixed and injected sc there
is a significant reduction in the insulin level.
• When the free insulin is added to Lente the equilibrium shifted to the
left by a mass action effect reducing the level of free zinc ions and
increasing the levels of insoluble zinc-insulin.
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27. Effect of storage
• When the admixture of the same form of insulin is kept refrigerated
(4)or at RT and injected sc.
• The plasma free insulin peak was greater for the refrigerated insulin
than then non refrigerated
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28. Effect of injection site
• The insulin is administer via the thigh or abdomen.
• The 125 iodine labelled soluble human insulin from sc and IM
injection sites in the thigh and abdomen.
• The purpose is to evaluate the importance of accidental IM injection
at these sites on insulin absorption.
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29. • Accidental IM injection in the thigh will considerably increase the
variability of insulin absorption and may thus impair glycemic
control in insulin dependent diabetics
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30. References
• Pharmaceutical Dosage Forms: Parenteral Medications volume:1
Second edition , Revised and expanded.
Edited by Kenneth E . Avis , Herbert A. Lieberman and Leon Lachman
• Biopharmaceuticals and pharmacokinetics a treatise by B.M BRAHMNKAR
AND SUNIL B. JAISWAL
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