Shruti Bhat PhD, MBA, Operations Excellence Expert
  • Home
  • About Shruti
  • Books
  • Insights
  • Operational Excellence
  • Research
    • Innovation Management
    • Leading Research and Development
    • Developer's Diary
  • Case Studies
  • Tools
    • Whitepapers
    • Articles >
      • Business Transformation
      • Process Improvement
      • Business Continuity
      • Change Management
      • Digital Transformation
      • Quality Improvement
    • Checklists and Templates
    • Free eBook
    • Videos
  • Blog
  • Engage Shruti
    • Consulting >
      • Operational Excellence Consulting
      • Business Transformation Consulting
      • Innovation Management Consulting
    • Workshops
  • Contact

Analytical considerations of mucosal drug delivery systems:

5/29/2009

0 Comments

 
As is the case with classical chemical substances, drug and diagnostic products that have their origin in biotechnology must meet standards that define their identity, strength, quality and purity. Although the basic requirements that apply to biotechnology products are the same as these that apply to classical chemical substances, the analytical methods that are required for evaluating the two types of materials and the considerations for their quality control are quite different. 
analytical considerations of mucosal drug delivery systems
Potency of Proteins: 

Three very reliable techniques employed for peptide estimation include-
  1. RIA
  2. Chromatography.
  3. Fast atom bombardment mass spectrometry. 

Potency determinations for proteins can range from complex bioassays that often use cell culture procedures to enzyme immunoassays and radio immunoassays (RIA) as well as more classical methods of chromatography.  Major attention must be given to quantitating the biological activity of the intact molecule as well as to determining whether the protein has been denatured or inactivated during the manufacturing process.  Intact proteins can have a disturbed secondary or tertiary structure, which can render these proteins partially or completely inactive. The correlation of bioactivity with classical assay procedures much as HPLC or immunoassays should be adopted as a long term goal so that these more precise methods of assay can eventually replace tedious and less precise bioassay methods. 

RIA techniques- 

RIA techniques exploit the specific and tight association of antibody with a peptide / protein drug in a variety of complex matrices.  The ability of a protein antigen to combine with its corresponding antibody is a structurally and conformationally specific interaction. Thus, if the protein or the antibody were conformationally altered i.e. denatured, a less than optimal protein-antibody interaction would occur. A drop in the immunochemical assay does not necessarily imply a drop in bioactivity since the decomposition products or the conformationally altered protein may still be bioactive. On the other hand, decomposition of the protein may not be reflected in the immunochemical assay as long as the antigenic determinant part of the protein molecule is intact and capable of reacting with the antibody. 

Merit/ demerits of RIA in peptide analysis-

  1. Long development times.
  2. Specificity cannot be easily changed.
  3. Detection is independent of intrinsic properties or derivation.
  4. Sensitivity is better with RIA than with chromatography.
  5. Difficult to recover if present in low concentrations (during sample preparation).
  6. May need LCMS for method validation.

HPLC techniques-

HPLC on the other hand was found to differentiate among the insulin from cows, pigs and men and to be both reproducible and stability indicating.  For insulin and insulin injections subjected to accelerated stability tests, the HPLC method detects the decomposition that cannot be detected by either the mouse blood glucose assay or the immunoassay.  

Merits / demerits of HPLC / GC in peptide analysis- 

  1. Short development times.
  2. Specificity can be modified.
  3. Adaptable Matrix dependence.
  4. Detection is dependent on intrinsic properties or derivation.
  5. Good sensitivity
  6. Relatively low assay throughput.
  7. Method can be validated.

Fast atom bombardment mass spectrometry:

This technique is also very useful in peptide/protein analysis.  A radio receptor assay has been described for insulin. Enzyme assays also have very high specificity and sensitivity.  A method for determining the particle size of zinc-insulin and its distribution in suspension formulations, based on the measurement of absorbance in the high UV-Visible region has been reported. 

In view of the complex structure of proteins, the correlation of bioactivity with classical assay procedures such as HPLC or immunoassays should be adopted to gain a greater confidence in the data generated. 

Toxicity and safety: 

For proteins and polypeptides being developed as drugs, preclinical studies have two complementary aims:-  

  1. to demonstrate potential utility and
  2. To rule out useless or harmful compounds without efficiency and economical.

​The tests include:

1. Efficacy testing:

The range of substances and potential action is so extensive that only a general account can be given of the principles underlying efficacy testing. The first need is to define the specific biological activity that is considered or believed to represent the mechanism of the therapeutic goal. This might be perceived as a change in a receptor or in an intracellular effector, a clear-cut biological response in cells, in vitro a more complex response in an animal. It is necessary to explore the principal effect of the candidate drug and the mechanism of that action in whatever test systems are available.

2. Toxicity testing:

This covers at least as broad an area of biological assessment of efficacy test. The need is to detect and characterize potentially harmful actions in such a way that an informed judgment can eventually be made between the likely therapeutic benefit and risk of treatment in deciding whether and how to undertake clinical trials or to apply for a product license. 

3. Program of toxicity testing: 

The tests included are: general pharmacology, acute toxicity, pharmacokinetics, 2-4 weeks repeat dose toxicity test in one or two species, local irritancy, antibody formation, second species multi-dose test, complete kinetics and metabolism, mutagenecity, reproduction toxicity, pharmacodynamics, endocrine effects, state of immune system and metabolism toxicity.

4. Pyrogens:

Pyrogen and bacterial endotoxins are detected by the conventional rabbit test, LAL testing or pyrogen evoked depression of plasma testing.

In the next post we shall discuss different routes available for administration of peptide / protein molecules.
Follow Shruti on Twitter, Facebook, YouTube, LinkedIn
0 Comments

Your comment will be posted after it is approved.


Leave a Reply.

    Shruti Bhat, global leader in business turnaround, operational excellence and continuous improvement
    To contact Dr. Shruti Bhat text or WhatsApp at 1.403.969.6219

    New Book Released!

    Revolutionizing Industries with Lean Six Sigma

    Shruti's YouTube Channel ...

    Picture

    Blog Categories

    All
    3D Printing
    Agile
    Artificial Intelligence
    Automation
    Biotechnology
    Books
    Business Continuity
    Business Turnaround
    Case Studies
    Change Management
    Checklists
    Chemical Industry
    Continuous Improvement
    Design Thinking
    Digitalization
    Drug Delivery
    External News Links
    Hall Of Fame
    Healthcare
    Hoshin Kanri
    HR Development
    Innovation
    Insights
    ISO
    Just In Time
    Kaizen
    Leadership
    LEAN
    Lean Six Sigma
    Life Sciences
    Machine Learning
    Manufacturing
    Medical Devices
    Mistake Proofing
    Motivational Cards
    MSMEs
    Nanotechnology
    Operational Excellence
    Packaging
    Patents
    Personal Products
    Process Improvement
    Product Development
    Productivity Increase
    QbD
    Quality Management
    R&D Leadership
    Robotics
    Service Industry
    Six Sigma
    Strategy
    Supply Chain Logistics
    Telecom Industry
    Templates
    TQM
    Videos
    Voice Of Customer
    Whitepaper
    Workshops

    Shruti's books...

    Picture
    top ten strategic decision-making tools for operational excellence
    shruti bhat, business process management, continuous improvement
    kaizen for pharmaceutcials, medical devices and biotech industry book by Dr Shruti Bhat
    Book on Continuous improvement tools by Dr Shruti Bhat
    kaizen for leaders, continuous process improvement tool to increase profit and organizational excellence by shruti bhat
    kaizen, shruti bhat, continuous improvement, quality, operations management
    how to lead a successful business transformation
    leading organizations through crisis
    emotional intelligence
    how to overcome challenges of creating effective teams
    modular kaizen Vs Blitz kaizen
    How to increase employee engagement as a new boss

Connect with Dr. Shruti Bhat at- ​Twitter, YouTube, LinkedIn​

© Copyright 1992- 2025 Dr. Shruti Bhat ALL RIGHTS RESERVED.
See Terms and Conditions for details on this site usage.
Subscribe to Operational Excellence Academy YouTube Channel
​Subscribe to Operational Excellence Academy YouTube Channel
SHRUTI BHAT, CONTACT
Click to connect.
Created by Macro2Micro Media