1. 1
Presented by:-
Mr. Mane Avinash A.
M.Pharm sem.-ÍÍ
Dept. of Pharmaceutics
Guided by:-
Mr. Galgatte U.C.
Associate Professor
Dept. of Pharmaceutics
P. E. SOCIETY’S MODERN COLLEGE OF
PHARMACY NIGDI,PUNE,44
2015-16
2. Peptides are short polymers formed from the linking,
in a defined order, of α-amino acids. The link between
one amino acid residue and the next is known as an
amide bond or a peptide bond.
2
3. Proteins are large organic compounds made of amino
acids arranged in a linear chain and joined together by
peptide bonds between the carboxyl and amino groups
of adjacent amino acid residues
3
4. Primary structure- The amino acid sequence.
Secondary structure- Regularly repeating local structures
stabilized by hydrogen bond.
Tertiary structure- The three dimensional structure of the
polypeptide.
Quaternary structure-The structure formed by 2 or more
polypeptide chains associated by non covalent forces.
4
6. 1. Erythropoietin used for production of RBC.
2. Tissue plasminogen activator is used for Heart attack,
Stroke.
3. Oxytocin maintain labor pain.
4. Bradykinin increases the peripheral circulation.
5. Somatostatin decrease bleeding in gastric ulcer.
6. Gonadotropin induce ovulation.
7. Insulin maintain blood sugar level.
6
7. 1. Transport and storage of small molecules.
2. Coordinated motion via muscle contraction.
3. Mechanical support from fibrous protein.
4. Generation and transmission of nerve impulses.
5. Enzymatic catalysis.
6. Immune protection through antibodies.
7. Control of growth and differentiation via hormones.
7
8. 1. Elimination by B and T cells.
2. Proteolysis by endo/exo peptidases.
3. Small proteins filtered out by the kidneys very
quickly.
4. Unwanted allergic reactions may develop (even
toxicity).
5. Loss due to insolubility/adsorption.
8
9. Encapsulated peptides or proteins in amino acids with
microspheres of approximately 10 micron in diameter ,
used for oral delivery.
Example: Insulin and heparin.
Orally administered insulin produces hypoglycemic
effect .
9
10. The ease of administration and higher degree
of patient compliance with oral dosage forms
are the major reasons for preferring to deliver
proteins and peptides by mouth.
10
11. protection against the metabolic barrier in GIT
absence of a carrier system for absorption of peptides
with more than three amino acids
Proteins are labile due to susceptibility of the pepti
de backbone to proteolytic cleavage
Prodrug approach
olefenic substitution, d‐amino acid substitution,
dehydro amino acid substitution, carboxyl reduction
11
12. 1. Amino acid modifications
Metkephamid, an analog of methionine
encephalin with substitution of glycine₂ by l-alanine
and modified methionine, readily penetrated across
the nasal mucosa with 54% bioavailability relative
to subcutaneous administration but was orally
inactive
12
13. 2. Hydrophobization
Hydrophobization of peptides may be attempted by two
approaches. The first is peptide backbone modification
to include more of hydrophobic amino acids; the second
would be covalent conjugation of a hydrophobic
moiety—for example, a lipid or polymeric tail.
Increasing the hydrophobicity of a peptide or
protein by surface modification using lipophilic
moieties may be of particular benefit to trans
cellular passive or active absorption by
membrane penetration or attachment,
respectively; or it may simply aid in the increased
stability of the protein.
13
14. EXAMPLE
lipophilic modification of TRH by covalent
conjugation of lauric acid to this tripeptide
(Lau-TRH). The derivative was more stable in
rat plasma and was rapidly converted to TRH
in the intestinal mucosal homogenate.
14
15. Formulating for delivery through the
gastrointestinal (GI) tract requires a multitude
of strategies
To alter the environment for maximum
solubility and enzyme stability of protein by
using formulation excipients such as
buffers surfactants and protease inhibitors
To promote absorption through the
intestinal epithelium
15
17. Bonding of (PEG) and alkyl groups fatty acid
radicals to produce desired amphiphilic oligomers
oligomers are conjugated to proteins or peptides to
obtain desired amphiphilic products
can resist excessive degradation of protein or
peptide drugs
technology reduces self‐association, increases penetra
tion and increases compatibility with formulation i
ngredients than parent drug
17
19. Oral delivery is the most sought after route of
administration for most of the drugs and
pharmaceutical products, which depends on
the drug’s molecular structure or weight
Transport mechanism of macromolecules
19
21. (A) Transport mechanism of bio drug through
the intestinal epithelium membrane,
(B) Probable mechanism of penetration
enhancer,
C) enzyme inhibitors,
(D) Representative mechanism of prodrug
absorption and its activation.
21
23. Sr.
no
.
Approach Examples Effects on
bioavailability
Drawbacks
1 Absorption
enhancers
Bile salts,
fatty acids,
Surfactants
(anionic,
cationic)
Enhanced
bioavailability by
increased
membrane
permeation
Available transport
systems of both
proteins/peptides and
undesirable molecules in
GIT
2 Enzyme
inhibitors
Sodium
glycocholate
, camostate
mesilate
Resisted enzymes
degradation in
stomach and
intestines
Produced severe side
effects in the treatment of
chronic diseases such as
diabetes, etc.
3 Mucoadhesi
ve
polymeric
systems
Thiolated
polymer
Site–specific
delivery and
improved
membrane
permeation
Limitation due to the
mucus turnover in
absorption sites
(intestine)
4 Prodrug
strategies
Phenyl
propionic
acid
Prodrug
permeability
improved 1608fold
than parent drug
Lack of methodology,
structural
complexity, stability
problem of protein 23
24. Desmopressin acetate (DDAVP) is a synthetic
analogue of 8 arginine vasopressin: ant
diuretic hormone. Marketed by Aventis
pharmaceutical and is approved for diabetes
insipidus.0.16 % bioavailable
Novartis and Roche pharmaceutical market
cyclosporine (small lyophilic mol. For graft
rej.) 30% bioavailability
24
25. Aim:
Design and In Vitro Characterization of
Buccoadhesive Drug Delivery System of Insulin
Preparation Method:
A buccoadhesive drug delivery system of
Insulin was prepared by solvent casting
technique and characterized in vitro by surface
pH, bio adhesive strength, drug release and skin
permeation studies. Sodium carboxymethyl
cellulose-DVP was chosen as the controlled
release matrix polymer.
25
26. Result:
it is concluded that the system is a
success as compared to the conventional
formulations with respect to invasiveness,
requirement of trained persons for
administration and most importantly, the first
pass metabolism.
26
27. Company Product
name
Formulation Development
phase
Product
Apollo Life
Science
Oradell Tablet Clinical
phase I b
Insulin, TNF-
blocker
Emisphere Eligen Tablet Phase II Calcitonin,
insulin, PTH,
heparin
Nobex/Bioco
n
HIM2 Liquid Abandoned Insulin,
enkephalin,
calcitonin
27
28. Company Product name Formulation Development
phase
Product
Oramed ORMD-0801
ORMD-0901
Capsule Phase I Insulin/Exena
tide
Diasome
pharmaceutic
als
Hepatic-
directed
vesicles-
insulin
(HDV-1)
Tablet Phase II/III Insulin
Diabetology Capsulin Capsule Phase II Insulin
Merrion
pharma
(Ireland)
with Novo-
Nordisk
Vetsulin Matrix tablet Phase I Insulin and
GLP-1
analogues
Chiasma
(Israel)
Octreolin Suspension Phase I
(phase I
completed,
phase III
enrolling
Octreotide
28
29. NAME OF
PUBLICATIO
N
PUBLICATIO
N NO.
TYPE DATE INVENTOR
Oral delivery
of modified
transferrin
fusion
proteins
US8129504
B2
Grant 6 march
2012
Christopher
p.Prior ,
Homoyoun
sodeghi,And
rew turner.
Peptide
library and
screening
systems
US5432018
A
Grant Jul 11, 1995 William J.
Dower,
Steren
E.cwirla,
Ronald
W.barrett
Peptide
conjugate
US5442043 Grant Aug 15,1995 Takeda
chemical
industries
29
30. 1. McNally Ej. protein formulation and delivery. In: Drug and
the pharmaceutical sciences.2nd ed. New York: Marcel
Dekker; 2000.p.99-125
2. Novel drug delivery system by Dr. D. K. Jain and Dr. D. T.
Baviskar Nirali prakashan Page no.14.1-14.7
3. Agarwal, V., Khan, M.A., 2001. Current status of the oral
delivery of insulin. Pharm. Tech. 25 (10), 76–90.
4. Antunes, F., Andrade, F., Ferreira, D., Morck, N.H.,
Sarmento, B., 2013. Models to predict intestinal
absorption of therapeutic peptides and proteins. Curr.
Drug Metab. 14 (1), 4–20.
5. Aoki, Y., Morishita, M., Asai, K., Akikusa, B., Hosoda, S.,
Takayama, K., 2005. Region dependent role of the
mucous/ glycocalyx layers in insulin permeation across
rat small intestinal membrane. Pharm. Res. 22 (11),
1854–1862.
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