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Suspension is a part of the liquid your insulin is mixed with, to change its action profile.

The three major suspension types you'll see are Isophane, Protamine Zinc, and Zinc suspensions. Neutral insulins do not use an added suspension.

A suspension is either minerals, proteins, or both, added to the insulin's diluting liquid to slow their absorption in the body and make them work longer.[1][2].

Suspended insulins are cloudy or milky in appearance, even before they have been rolled; they must be rolled or resuspended before use or they will not be properly effective.

Analog mixed insulins are suspended by the use of protamine to create special insulin crystals. These mixes also begin with the basic insulins: Humalog, Novolog and NovoRapid.

R/Neutral insulinsEdit

R or neutral insulin is basically zinc insulin crystals dissolved in clear fluid with nothing added to alter its action or speed[3]--no suspension.   R/Neutral insulins also have no buffer[4].

The zinc suspension of Lente-type insulin binds R/Neutral, causing the short-acting insulin to slow, losing its short-acting effect[5][6], so combining them would be incompatible[7].

From 1921 to the 1930's when PZI was developed, R was the only kind of insulin available.


R/Neutral Insulins[8]

All fast-acting:

NONE

Isophane suspension insulinsEdit

NPH or isophane insulins combine protamine, zinc and insulin. The difference between NPH and its older brother, PZI, is the amount of protamine in the formula; PZI insulin has more protamine in it. The salmon-derived protamine is less readily absorbed than insulin itself; basically the system must absorb all of the protamine present in the formulation before the absorption process of the insulin can begin[9].

Mixed insulins contain a given ratio of R/Neutral and NPH/isophane insulin. These are all phosphate buffer insulins, just as NPH/isophane insulin without any addition of R/Neutral is. The phosphate buffer makes them incompatible with the Lente-type insulins for combining[10][11]. These mixed insulins are a combination of intermediate-acting NPH/isophane insulin with short-acting R/Neutral producing intermediate-acting insulins.


Isophane suspension

All intermediate-acting:

Generic Names:

NPH, isophane[12]
Mixed insulins, biphasic[13]

Brand Names: Non-analog,
non-mixed Human:

Actrapid, Humulin I
Humulin N, Insuman Basal
Insulatard, Novolin N
Protaphane
ReliOn/Novolin NPH

Brand Names: Non-analog,
non-mixed Bovine:

Hypurin Bovine Isophane
Iletin I NPH

Brand Names: Non-analog,
non-mixed Porcine:

Hypurin Porcine Isophane
Iletin II NPH
Pork Insulatard

Brand Names: Non-analog,
Mixed Human:

Actraphane 20/80
Actraphane 30/70
Actraphane 50/50
Humulin 50/50, Humulin 70/30
Humulin M2, Humulin M3
Humulin M5
Insuman Comb 15
Insuman Comb 25
Insuman Comb 50, Mixtard 10
Mixtard 20, Mixtard 30
Mixtard 40, Mixtard 50
Novolin 70/30
ReliOn/Novolin 70/30

Brand Names: Non-analog,
Mixed Porcine:

Hypurin Porcine 30/70 Mix
Pork Mixtard 30

Generic Names: Analog Mixed

Aspart, Lispro

Brand Names: Analog Mixed:

Humalog 75/25
Humalog Mix 25
Humalog 50/50
Humalog Mix 50
Novolog Mix, NovoMix 30

Protamine zinc suspension insulinsEdit

The difference between PZI and its younger brother, NPH, is the amount of protamine in the formula; PZI insulin has more protamine in it. The salmon-derived protamine is less readily absorbed than insulin itself; basically the system must absorb all of the protamine present in the formulation before the absorption process of the insulin can begin[14]. Since there's more protamine present in Protamine Zinc insulin, it takes the body longer to absorb it before going on to the absorption of the insulin itself. The longer absorption period of the extra protamine is how PZI has more duration. Both NPH/isophane and PZI insulins use phosphate buffers which makes them incompatible with the Lente-type insulins for combining[15][16].


Protamine Zinc suspension[17]

All slow-acting:

Generic Names:

PZI

Brand Names: Bovine/Porcine:

PZI Vet

Brand Names: Bovine:

BCP PZI
Insuvet Protamine Zinc
Hypurin Vet Protamine Zinc
Hypurin Bovine Protamine Zinc

Zinc suspension insulinsEdit

The Lente family of insulins consist of insulin crystals of basically two different sizes--the larger ultralente and the smaller semilente insulin crystals, with added zinc. Combining the short-acting semilente with the slow-acting ultralente in a ratio of 3 parts semilente to 7 parts ultralente produces the intermediate-acting Lente insulin.

It is the addition of zinc and the size of their respective crystals which controls the rate of their absorption, as the only protein present in the Lente family is the insulin itself; they all have acetate buffers[18].

The phosphate buffer used for both NPH/isophane and PZI insulins is incompatible with Lente-type insulins. Phosphates alter the profile of Lente-type insulins, making them about as fast-acting as R/Neutral[19][20].

The zinc suspension of Lente-type insulin binds R/Neutral, causing the short-acting insulin to slow, losing its short-acting effect[21][22], so combining them would be incompatible as well[23].


Zinc suspension

Generic Names:
Rapid-acting:

semilente
Insulin Zinc Suspension (amorphous)[24]

Brand Names:
Rapid-acting Porcine:

Novo Semilente MC

Generic Names:
Intermediate-acting:

Lente
Insulin Zinc Suspension[25]

Brand Names:
Intermediate-acting Human:

Humulin L, Novolin L
Monotard

Brand Names:
Intermediate-acting Bovine:

Insuvet Lente
Hypurin Bovine Lente
Iletin I Lente

Brand Names:
Intermediate-acting Porcine:

Caninsulin, Vetsulin
Monotard Pork, Iletin II Lente

Generic Names:
Slow-acting:

ultralente
Insulin Zinc Suspension (crystalline)[26]

Brand Names:
Slow-acting Human:

Humulin U, Humulin Zn
Novolin U, Ultratard

ReferencesEdit

  1. Diabetes Forecast-ADA, 2006-Page 5
  2. Endotext.com-Insulin-Pharmacology, Types of Regimens & Adjustments
  3. US FDA-Humulin R
  4. Auburn University: Insulin Preparations-Regular Insulin
  5. Intermediate-Acting Insulin Preparations: NPH (Isophane) & Lente Diabetes Care-1980
    Note--in 1980, there was only beef Lente-type insulin--no pork or r-DNA/GE/GMLente insulins
  6. Resource Guide-2005-American Diabetes Association
  7. RxEd.org-Insulin Therapy-Mixing Precautions
  8. Insulin-InChem
  9. Auburn University: Insulin Preparations-NPH
  10. Auburn University: Insulin Preparations
  11. RxEd.org-Insulin Therapy-Mixing Precautions
  12. Insulin-InChem
  13. Insulin-InChem
  14. Auburn University: Insulin Preparations-NPH
  15. Auburn University: Insulin Preparations
  16. RxEd.org-Insulin Therapy-Mixing Precautions
  17. Insulin-InChem
  18. Auburn University: Insulin Preparations-Lente Insulins
  19. Auburn University: Insulin Preparations-Lente Insulins
  20. RxEd.org-Insulin Therapy-Mixing Precautions
  21. Intermediate-Acting Insulin Preparations: NPH (Isophane) & Lente Diabetes Care-1980
    Note--in 1980, there was only beef Lente-type insulin--no pork or r-DNA/GE/GMLente insulins
  22. Resource Guide-2005-American Diabetes Association
  23. RxEd.org-Insulin Therapy-Mixing Precautions
  24. Insulin-InChem
  25. Insulin-InChem
  26. Insulin-InChem

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