Non-invasive formulation approaches to pharmaceutical proteins and peptides

1. Non-injectable formulation approaches
to pharmaceutical proteins and
peptides
Nawin Pudasaini
Study number: L11012

2. Buccal Pulmonary
Oral
Non- invasive
route
Sublingual
Rectal
Occular
Intranasal Transdermal

3. Rationale for oral administration
 Simple, convenient, preferred by the patients
 Prevent pain, discomfort, infections & improve
patients’ compliance.
 Cheap manufacturing.

4. Challenges
Dosage form stability issues
Enzymatic degradation
Poor intestinal absorption Oral bioavailability < 1%
Advantage
Mimics the physiological insulin
Patient compliance

5. Formulation approaches
API Chemical modification
Absorption enhancer
Excipeint
Enzyme inhibitors
Mucoadhesive polymer
Liposomes
Nanoparticles
Formulation vehicles Microspheres
Microemulsions
Mucoadhesive polymeric systems

6. Proposed formulation hypothesis
• Two strategies to protect insulin from protease digestion.
Stomach: enteric coating
Intestine: enzyme inhibitors
Other tablet ingredients
Insulin
Absorption enhancer
Enzyme inhibitor
Mucoadhesive polymer

7. Proposed tablet formulation
Ingredients Amount per tab.
Recombinant DNA insulin(modified) 2.75 mg
Zonula Occludens Toxin 1 mg
Chitosan TBA 5 mg
Soybean 0.75 mg
Povidone 5 mg
Cross-linked povidone 5 mg
Magnesium stearate 1 mg
Talc powder 9 mg
Micro Crystalline Cellulose 70.5 mg
Total = 100 mg

8. Manufacturing
• Dry mixing
• Direct compression
• Enteric coating
Eudragit S 100

9. Zona occluden How it works?? Soybean
improve protects from
permeability enzymatic
degradation
Chitosan
increase
mucoadhesion

10. Problems…….
• Insulin-Excipient compatibility
• Stability of insulin in the formulation

11. Conclusion……
• Clinical trials (I &II) suggests bioavailability ~5% may
result in an acceptable glucose-lowering effect.
• Enhancement of bioavailability further, possibly by
combining with other formulation approach will
result in use of very low amount of insulin in
controlling glucose levels orally.