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Peptides and Proteins Formulation

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Pharmaceutical excipients in the formulation of peptides and proteins. Polyhydric alcohols ... Formulation of peptides and proteins as lyophilized dosage form ... – PowerPoint PPT presentation

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Title: Peptides and Proteins Formulation


1
Peptides and Proteins Formulation
  • Mahmoud R. Jaafari, PhD
  • Prof. of Pharmaceutics

2
Introduction
3
Overview
  • Structure of peptide and protein
  • Solubility of peptides and proteins
  • The stability of peptides and proteins
  • Formulation of therapeutic peptides and proteins
    as parenteral solutions
  • Formulation of therapeutic peptides and proteins
    as lyophilized powder
  • Formulation of therapeutic peptides and proteins
    as parenteral suspensions

4
Protein structure
5
Protein Folding
  • Highly simplified schematic representation of the
    folding of a polypeptide chain in water, In the
    unfolded chain, side-chain and main-chain groups
    interact primarily with water, even if they are
    hydrophobic and the interaction is unfavorable.
    Burying the hydrophobic groups in the interior of
    a compact structure enables them to interact with
    each other (blue line), which is favorable, and
    leaves polar side chains on the surface where
    they can interact with water (red lines). The
    polar backbone groups that are buried along with
    the hydrophobic side chains must make hydrogen
    bonds to each other, as bulk water is no longer
    available.

6
Bonds that stabilize folded proteins
7
Solubility of peptides and proteins
  • 1) Nature of peptides and proteins
    (Hydrophobicity of peptides and proteins)

8
Solubility of peptides and proteins
  • 2) Effects of salt concentration

9
Solubility of peptides and proteins
  • 3) Effects of pH
  • Solubility of beta-lactoglobulin as a function of
    pH at several NaCl concentrations

10
Solubility of peptides and proteins
  • 4) Effects of organic solvents
  • 5) Effects of temperature

11
The stability of Peptides and Proteins
12
Physical Instability
  • 1) Denaturation
  • Heat Reversible and irreversible
  • The optical rotation at 366 nm as a function of
    temperature of bovine pancreatic ribonuclease A

13
Physical Instability
14
Physical Instability Denaturation
  • Changes of pH
  • Detergents
  • Water soluble organic compound
  • Salts Hofmeister series

15
Physical Instability aggregation
  • Aggregation vs self-association

16
Physical Instability
  • Precipitation

17
Physical Instability
  • Surface adsorption

18
Chemical Instability Deamidation
  • pHlt4

19
Chemical Instability Deamidation
  • pHgt6

20
Chemical Instability
  • Prevention of deamidation

21
Chemical Instability Protein Oxidation
22
Chemical Instability
  • Prevention of Protein Oxidation

23
Chemical Instability Racemisation
  • Alkaline Media

24
Chemical Instability Proteolysis
25
Chemical Instability Beta elimination
26
Chemical Instability Disulphid formation
(Exchange)
27
Formulation of peptides and proteins as
parenteral solutions
  • Introduction
  • Preformulation studies
  • Formulation development

28
Formulation of peptides and proteins as
parenteral solutions
  • Buffer system

29
Formulation of peptides and proteins as
parenteral solutions
  • pH of vehicle
  • Solubility of peptides and proteins

30
Selection of solvent system (Cosolvents)
31
Antimicrobial preservation
32
Choice of container
33
Pharmaceutical excipients in the formulation of
peptides and proteins
  • Albumin
  • Amino acids
  • Carbohydrates

34
Pharmaceutical excipients in the formulation of
peptides and proteins
  • Chelating agents and antioxidants

35
Pharmaceutical excipients in the formulation of
peptides and proteins
  • Cyclodextrins

36
Pharmaceutical excipients in the formulation of
peptides and proteins
  • Surfactants

37
Pharmaceutical excipients in the formulation of
peptides and proteins
  • Polyhydric alcohols
  • Polyethylene glycol

38
Selection of excipients DSC
39
Selection of excipients DSC
40
Accelerated stability studies
  • Gel Filtration Column Chromatography

41
Accelerated stability studies GPC
42
Accelerated stability studies GPC
43
Formulation of peptides and proteins as
lyophilized dosage form
  • Introduction
  • Process Details

44
Formulation of peptides and proteins as
lyophilized dosage form
45
Formulation of peptides and proteins as
lyophilized dosage form
  • Protein denaturation during lyophilization
  • Freeze- Thaw stability
  • Stability during drying

46
Formulation components for lyophilization
  • Buffers
  • Bulking agents
  • Tonicity modifiers
  • Stabilizer

47
Formulation components for lyophilization
  • Cryoprotectives

48
Formulation components for lyophilization
  • Lyoprotectives

49
Formulation of peptides and proteins as
parenteral suspensions
  • Introduction

50
Types of suspensions and particle formation
  • In situ particle formation
  • Crystalline suspensions
  • Amorphous suspensions
  • Crystalline and amorphous mixture
  • Crystalline and solution mixture
  • Combination of particle and vehicle

51
In situ particle formation Crystalline
suspensions
52
In situ particle formation Crystalline
suspensions
53
In situ particle formation Crystalline
suspensions
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