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Parenteral Delivery  Strathclyde 2009 annotated
Parenteral Delivery   ,[object Object]
Original syringe from 1856, Royal College of Surgeons, Edinbourgh, Scotland ,[object Object]
Parenteral Routes ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Avoiding First Pass effect Heart Gut lumen Liver Circulation i.v. i.m. s.c. Buccal Pulmonary In oral delivery, veins from the gut pass first through the Liver (hepatic portal system). Buccal & Pulmonary avoid this barrier
Parenteral Delivery   ,[object Object],[object Object],[object Object],[object Object],[object Object]
Small Volume Injectables: immediate formulations ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Small Volume Injectables: depot formulations ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Effect of particle size: penicillin G procaine i.m  (Buckwater & Dickison, 1958).  300,000 unit/ml administered to rabbits Serum Conc. (units/ml)
Effect of aluminium monostearate in penicillin G procaine suspension . Rabbits 300, 000 units per ml.  After Buckwater & Dickison 1958 m.i.c. 0.03 units /ml Serum Conc. (units/ml) 0  1  2  3  4  5  6  7  Days
The body ,[object Object],[object Object],[object Object],[object Object],[object Object]
Water in the body ,[object Object],[object Object],0 20 40 60 80 T.B.W I.C.F. E.C.F. Plasma Volume Blood Volume
Body water ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Infant – 75% water
Adult 60% water ,[object Object],Ectomorph Mesomorph or Endomorph ?
The Elderly - 45% water
Drug Movement
Concentration of drug at site of action and persistence of drug in the body ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Biopharm 1-II -1 ELIMINATION Wood rate of Eqm 2
The Importance of a blood supply...
This video illustrates movement of material from large vessels to the  Capillary bed
Parenteral Delivery ,[object Object]
Blood Flow ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Blood flow  Tissue Mass (Litres/min)  (% Total body weight )
Other vascular issues Day 1  Day 5
Tissue necrosis Day 10  Brown Recluse Spider (Colorado)
Disorders of venous return ,[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Flow per g tissue and Equilibrium
Drug Plasma Concentration-Time Profile
Distribution ,[object Object]
Capillary Permeability ,[object Object],[object Object]
Capillary Permeability: Lipid soluble molecules ,[object Object]
Capillary Permeability: Water soluble molecules ,[object Object],[object Object],[object Object]
[object Object],Effect of protein Binding on Distribution Rate Drug has plenty of time to equilibrate
Effect of protein Binding on Distribution Rate ,[object Object],Blood passed the delivery site very quickly therefore protein binding is important – wouldn’t see this in peripheral tissue because blood flow slower
The Plasma Concentration - Time profile ,[object Object],[object Object],10 0 0  1  2  3  4
Volume of distribution 10 1 0.1 3 600 mg dose At T 0 , Ct 0  = 3 ug/ml 0  1  2  3  4  Vd = 600/3 = 200 litres If weplot the data on a log axis and extrapolate back to zero, we can estimate the  size of the compartment we are draining from
Body fat Less VD than predicted for Water soluble drugs:  Higher Concentration
Body fat More VD than predicted for Lipid soluble drugs:  Lower Concentration  & slow equilibrium
Injection causes damage
Tissue reaction after subcutaneous injection  of a suspension of insulin crystals Areas of collagen bands and vacuolated tissue
Foreign body reaction ,[object Object]
Foreign body reaction ,[object Object],[object Object]
Muscle damage after intramuscular injection Necrotic muscle tissue Scarring occurs on the inside as well
Tissue damage after intramuscular or intralipomateous injection in pigs ,[object Object],Intralipomateous Intramuscular
Injection into buttocks (MRI guided) Treating an area around the pelvis Local to numb pain
Thickness of subcutaneous fat layer in man at injection site ,[object Object],Men are more prone to injection site damage than women because of the gender effect on fat distribution
Parenteral Delivery ,[object Object],[object Object],[object Object]
Parenteral Delivery Unabsorbed drug In solution   Membrane Membrane Bound Plasma  & ECF ICF Storage Sites Receptors Only unbound, unionised  drug can cross membrane Ionised Non Ionised Ionised Non Ionised Ionised Non Ionised
Thiopentone kinetics ,[object Object],[object Object]
REDISTRIBUTION
i.m. Injection of [ 131 I] NaI
[I-131] iodide kinetics 0.1h ,[object Object],[object Object]
[I-131] iodide kinetics 1.8h ,[object Object]
[I-131] iodide kinetics 5.6h ,[object Object],[object Object]
[I-131] iodide kinetics 7 days ,[object Object]
[I-131] iodide kinetics ,[object Object],[object Object],[object Object]
i.m. kinetics ,[object Object],[object Object],[object Object],[object Object],1 2 1-2
Thiopentone kinetics ,[object Object]
Guanethidine kinetics Plasma Liver Kidney Skeletal muscle Heart muscle Distribution following i.v. administration In this case the drug has been  accumulated in a tissue by an active process. Guanethidine accumulates in synaptic vesicles at the neuromuscular junction
Hazards of parenteral delivery ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Issues ,[object Object],[object Object],[object Object],[object Object]

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Strath Parenteral 2009 Annotated

  • 1. Parenteral Delivery Strathclyde 2009 annotated
  • 2.
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  • 5. Avoiding First Pass effect Heart Gut lumen Liver Circulation i.v. i.m. s.c. Buccal Pulmonary In oral delivery, veins from the gut pass first through the Liver (hepatic portal system). Buccal & Pulmonary avoid this barrier
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  • 9. Effect of particle size: penicillin G procaine i.m (Buckwater & Dickison, 1958). 300,000 unit/ml administered to rabbits Serum Conc. (units/ml)
  • 10. Effect of aluminium monostearate in penicillin G procaine suspension . Rabbits 300, 000 units per ml. After Buckwater & Dickison 1958 m.i.c. 0.03 units /ml Serum Conc. (units/ml) 0 1 2 3 4 5 6 7 Days
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  • 14. Infant – 75% water
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  • 16. The Elderly - 45% water
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  • 19. The Importance of a blood supply...
  • 20. This video illustrates movement of material from large vessels to the Capillary bed
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  • 23. Other vascular issues Day 1 Day 5
  • 24. Tissue necrosis Day 10 Brown Recluse Spider (Colorado)
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  • 35. Volume of distribution 10 1 0.1 3 600 mg dose At T 0 , Ct 0 = 3 ug/ml 0 1 2 3 4 Vd = 600/3 = 200 litres If weplot the data on a log axis and extrapolate back to zero, we can estimate the size of the compartment we are draining from
  • 36. Body fat Less VD than predicted for Water soluble drugs: Higher Concentration
  • 37. Body fat More VD than predicted for Lipid soluble drugs: Lower Concentration & slow equilibrium
  • 39. Tissue reaction after subcutaneous injection of a suspension of insulin crystals Areas of collagen bands and vacuolated tissue
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  • 42. Muscle damage after intramuscular injection Necrotic muscle tissue Scarring occurs on the inside as well
  • 43.
  • 44. Injection into buttocks (MRI guided) Treating an area around the pelvis Local to numb pain
  • 45.
  • 46.
  • 47. Parenteral Delivery Unabsorbed drug In solution Membrane Membrane Bound Plasma & ECF ICF Storage Sites Receptors Only unbound, unionised drug can cross membrane Ionised Non Ionised Ionised Non Ionised Ionised Non Ionised
  • 48.
  • 50. i.m. Injection of [ 131 I] NaI
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  • 58. Guanethidine kinetics Plasma Liver Kidney Skeletal muscle Heart muscle Distribution following i.v. administration In this case the drug has been accumulated in a tissue by an active process. Guanethidine accumulates in synaptic vesicles at the neuromuscular junction
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  • 60.