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 or Novolog/NovoRapid.

The long-acting analog insulins Lantus and Levemir don't have the "traditional" types of suspension but they are prolonged by other means. Lantus doesn't form crystals until it's under the skin; the crystals are slow to absorb. Levemir uses a binding to albumin in the bloodstream to prolong its action.

Contents 1 R/Neutral insulins-no suspension 2 Isophane suspension insulins 3 Protamine zinc suspension insulins 4 Zinc suspension insulins 5 References

R/Neutral insulins-no suspensionEdit

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 short-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. ^[4]

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. ^[4][7] 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 [8] Mixed insulins, biphasic[8]
Brand Names: Non-analog, non-mixed Human:	Actrapid, Humulin I,Humulin N, Insuman Basal, Insulatard, Novolin N Protaphane, ReliOn/Novolin NPH, Winthrop Basal, Huminsulin Basal, Humulina NPH, Humuline NPH, Umuline NPH, Insuhuman Basal
Brand Names: Non-analog, non-mixed Bovine:	Hypurin Bovine Isophane, Iletin NPH Betasint Bovine NPH
Brand Names: Non-analog, non-mixed Bovine/Porcine:	Iletin I NPH
Brand Names: Non-analog, non-mixed Porcine:	Hypurin Porcine Isophane Iletin II NPH, Pork Insulatard Betasint Porcine NPH
Brand Names: Non-analog, Mixed Human:	Actraphane 10/90, Actraphane 20/80 Actraphane 30/70, Actraphane 40/60 Actraphane 50/50, Humulin 10/90, Humulin 20/80,Humulin 40/60, Humulin 50/50, Humulin 70/30, Humulin M2, Humulin M3 Humulin M5, Insuman Comb 15, Winthrop Comb 15, Insuman Comb 25 Winthrop Comb 25,Insuman Comb 30 Winthrop Comb 30, Insuman Comb 50, Winthrop Comb 50, Mixtard 10, Mixtard 20, Mixtard 30, Mixtard 40, Mixtard 50 Novolin 70/30, ReliOn/Novolin 70/30, Penmix 10, Penmix 20, Penmix 30, Penmix 40, Penmix 50 Huminsulin Profil I, Huminsulin Profil II, Huminsulin Profil III, Huminsulin Profil IV, Humulina 10/90, Humulina 20/80, Humulina 30/70, Humulina 40/60, Humulina 50/50, Humuline 10/90, Humuline 20/80, Humuline 30/70, Humuline 40/60, Humuline 50/50, Umuline Profil 30, Umuline Profil 20, Isuhuman Comb 25, Insuhuman Comb 15, Insuhuman Comb 25, Insuhuman Comb 50 Humulin M, Humulin M1, Humulin M4, Novolin 30R
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.^[9] 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. ^[4] 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. ^[4][7]

Protamine Zinc suspension [8]
	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
Brand Names: Human:	ProZinc

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. ^[4]

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. ^[4][7]

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 as well ^[7]

Zinc suspension
	Short-acting:
Generic Names:	semilente Insulin Zinc Suspension (amorphous) [8]
Brand Names: Porcine:	Novo Semilente MC Insulinum semilente CHO
Brand Names: Bovine/Porcine:	Iletin I Semilente
	Intermediate-acting
Generic Names:	Lente, Insulin Zinc Suspension [8]
Brand Names: Human:	Humulin L, Novolin L, Monotard Humulina L, Humuline Long Umuline Zinc Compose
Brand Names: Bovine:	Insuvet Lente, Hypurin Bovine Lente Iletin Lente, Betasint Bovine Lente
Brand Names: Porcine:	Caninsulin, Vetsulin Monotard Pork, Iletin II Lente Betasint Porcine Lente, Lente CHO
Brand Names: Bovine/Porcine:	Iletin I Lente
	Long-acting
Generic Names:	ultralente Insulin Zinc Suspension (crystalline) [8]
Brand Names: Human:	Humulin U, Humulin Zn Novolin U, Ultratard Humulina Ultralenta, Humuline Ultralong, Umuline Zinc
Brand Names: Bovine/Porcine:	Iletin I Ultralente

ReferencesEdit

1. ↑ Diabetes Forecast-page 5. American Diabetes Association (2006).
2. ↑ Insulin-Pharmacology, Types of Regimens & Adjustments. Endotext.org.
3. ↑ Humulin R. Eli Lilly.
4. ↑ ^{4.0 4.1 4.2 4.3 4.4 4.5 4.6} DeRuiter, Jack. Insulin Preparations-Regular Insulin. Auburn University.
5. ↑ ^{5.0 5.1} Deckert, T. (1980). Intermediate-Acting Insulin Preparations: NPH (Isophane) & Lente. Diabetes Care.
   Note--in 1980, there was only beef Lente-type insulin--no pork or r-DNA/GE/GMLente insulins
6. ↑ ^{6.0 6.1} Resource Guide. American Diabetes Association (2005).
7. ↑ ^{7.0 7.1 7.2 7.3 7.4} Insulin Therapy-Mixing Precautions. RxEd.org.
8. ↑ ^{8.0 8.1 8.2 8.3 8.4 8.5 8.6} Insulin. InChem.
9. ↑ Greco, Deborah (2010). Treating Diabetes Mellitus in Dogs and Cats. Western Veterinary Conference.