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Stage 3 Case 4 > Insulin formulations > Flashcards

Insulin formulations Flashcards

1
Q

3 principles of insulin formulation

A

Insulin
Excipients
Device

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2
Q

What would call each insulin molecule?

A

Monomer

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3
Q

What would call 2 insulin molecules?

A

Dimer

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4
Q

What would call 6 insulin molecules (3 dimers)?

A

Hexamer

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5
Q

How are dimers stabilized?

A

Hydrophobic interactions between GluB21 and GlyB23 of one monomer and ProB28 on another monomer.

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6
Q

How are hexamer formulation stabilized?

A

By Zn2+ and phenol

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7
Q

Faster acting insulin

A

Bolus
Stabilized monomeric form (easily break off from multimeric form)
Increased absorption rate (more soluble)

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8
Q

Longer acting insulin

A

Basal
Stabilized multimeric form (takes longer to break off)
Reduced absorption rate. (Chunkier and less soluble)

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9
Q

More soluble insulin analogues (rapid)

A

Lispro
Aspart
Glulisine

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10
Q

Less soluble insulin analogues (Intermediate/long)

A

Degludec
Detemir
Glargine

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11
Q

What was changes in Insulin lispro (Humalog)?

A

ProB28 and LysB29 are swapped

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12
Q

What is the effect of the changes in insulin lispro?

A

Proab28 is responsible for stabilizing the insulin dimer. So the swap is enough to destabilase the dimer and less likely to bind to zinc.
Most stable in monomer form and more soluble than native insulin.

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13
Q

What was changes in Insulin Aspart (NovoRapid)?

A

ProB28 switched with Asp

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14
Q

What is the effect of the changes in Insulin Aspart?

A

Proab28 is responsible for stabilizing the insulin dimer. So the swap is enough to destabilase the dimer and less likely to bind to zinc.
Most stable in monomer form and more soluble than native insulin.

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15
Q

What was changes in Insulin glulisine?

A

AsnB3 to Lys

LysB29 to Glu

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16
Q

What is the effect of the changes in Insulin glulisine?

A

Decreased hexamer formation
Monomer stabilization
Enhance solubility.

17
Q

What was changes in Insulin glargine?

A

AsnA21 to Gly

Add ArgB31 and 32

18
Q

What is the effect of the changes in Insulin glargine?

A

Less soluble at physiological pH

19
Q

What was changes in Insulin dugledec?

A

Remove ThrB30 and attach a longer chain molecule at LysB29.

20
Q

What is the effect of the changes in Insulin deugledec?

A

The long chain attachment helps to stabilize the insulin in hexametric structure. Once the zinc diffuses out, the hexamers disassemble releasing monomer. Monomers diffuse into circulation from depot.

21
Q

What was changes in Insulin detemir?

A

ThrB30 removed

Add myristic acid at LysB29.

22
Q

What is the effect of the changes in Insulin detemir?

A

Long hydrocarbon chain reduces solubility of the insulin analogue. But its main action is to help it bind to albumin in the blood.

23
Q

Two types of inulin formulations

A

Solutions

Suspensions

24
Q

Insulin Solutions action

A

Rapid onset

Shorter acting

25
Q

Insulin Suspensions action

A

Slower onset

Longer acting

26
Q

NPH (isophane) insulin

A

Neutral protamine hagedorn

27
Q

What is Neutral protamine Hagedorn (NPH)

A

Protamine complexes with insulin to form aggregates through ionic
interactions – suspension.
Prolongs insulin release – Intermediate-acting formulations.

Stage 3 Case 4 (11 decks)

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