The document discusses protein and peptide drug delivery systems. It begins by defining proteins and peptides, noting that proteins are molecules composed of over 50 amino acids, while peptides are molecules composed of less than 50 amino acids. It then discusses how scientific advances in molecular and cell biology have led to the development of recombinant DNA and hybridoma technology to produce protein products. The document provides examples of marketed protein and peptide drugs and discusses challenges with delivering these drugs orally due to their large molecular size and susceptibility to enzymatic degradation. It explores approaches to protein and peptide delivery including non-parenteral systemic delivery methods and various considerations for developing delivery systems for these pharmaceuticals.
Barriers to Protein and peptide drug delivery system JaskiranKaur72
Protein and peptide DDS are novel systems of drug delivery.
The successful delivery of peptide and protein-based pharmaceuticals is primarily determined by its ability to cross the various barriers presented to it in the biological milieu. Various barriers encountered are-
1 Physiological Barrier
2 Intestinal Epithelial barriers
3 Capillary Endothelial Barrier
4 Blood-Brain barrier (BBB)
Barriers to Protein and peptide drug delivery system JaskiranKaur72
Protein and peptide DDS are novel systems of drug delivery.
The successful delivery of peptide and protein-based pharmaceuticals is primarily determined by its ability to cross the various barriers presented to it in the biological milieu. Various barriers encountered are-
1 Physiological Barrier
2 Intestinal Epithelial barriers
3 Capillary Endothelial Barrier
4 Blood-Brain barrier (BBB)
Protein and Peptide drug delivery system are the Novel drug Delivery System. Proteins and peptides are the most abundant components of biological cells. They exist functioning such as enzymes, hormones, structural element and immunoglobulin. Proteins and peptides are therefore almost exclusively administered by the parenteral route. Although parenteral administration serves the purpose, it has several shortcomings. It encounters, many barriers affecting its stability, such as poor cellular membrane permeability at the GIT site, enzymatic degradation (various proteases), and first-pass hepatic metabolism.
Description about a type of activation modulated drug delivery system, which a type of control drug delivery system.
Also, give a detailed description about each subclassification.
CrDDS is one which delivers the drug at a predetermined rate, for locally or systematically, for a prolong period of time.
Protein and Peptide drug delivery system are the Novel drug Delivery System. Proteins and peptides are the most abundant components of biological cells. They exist functioning such as enzymes, hormones, structural element and immunoglobulin. Proteins and peptides are therefore almost exclusively administered by the parenteral route. Although parenteral administration serves the purpose, it has several shortcomings. It encounters, many barriers affecting its stability, such as poor cellular membrane permeability at the GIT site, enzymatic degradation (various proteases), and first-pass hepatic metabolism.
Description about a type of activation modulated drug delivery system, which a type of control drug delivery system.
Also, give a detailed description about each subclassification.
CrDDS is one which delivers the drug at a predetermined rate, for locally or systematically, for a prolong period of time.
Protein and peptide drug delivery systemSagar Savale
Protein and Peptide drug delivery system are the Novel drug Delivery System. Proteins and peptides are the most abundant components of biological cells. They exist functioning such as
enzymes, hormones, structural element and immunoglobulin. The distinction between peptides and proteins is having a peptide contains less than 20 amino acids, having a molecular weight less, while a protein possesses 50 or more amino acids and its molecular weight lies above this value. The most of pharmaceutical proteins and peptides are absorbed IM, IV and Subcutaneous route of Absorption, but the oral route is more convenient for absorption of protein as compared to other. Various problems associated with administration of protein and peptide drugs are needed to overcome by different pharmaceutical approaches. Several approaches available for
maximizing pharmacokinetic and pharmacodynamics properties are chemical modification,
formulation vehicles, mucoadhesive polymeric system, use of enzyme inhibitors, absorption
enhancers, penetration enhancers etc.
Liposomes are concentric bilayered vesicles in which an aqueous core is entirely enclosed by a membranous lipid bilayer mainly composed of natural or synthetic phospholipids.
Liposomes are spherical microscopic vesicles consisting phospholipids bilayers which enclose aqueous compartments.
The size of a liposome ranges from some 20 nm up to several micrometers.
Liposomes were first produced in England in 1961 by Alec D. Bangham, who was studying phospholipids and blood clotting.
Small unilamellar vesicles (SUV), 25 to 100 nm in size that consist of a single bilayer
Large unilamellar vesicle (LUV), 100 to 500 nm in size that consist of a single bilayer
Multilamellar vesicle (MLV), 200 nm to several microns, that consist of two or more concentric bilayer
USFDA Approval Process For Drug Products & Biological Product i.e NDA Vs. BLA
Comparison of NDA and BLA application process in USA. IND, NDA, ANDA & BLA dossier submission procedure.
PROTEIN AND PEPTIDE DELIVERY THROUGH ORAL ROUTEAkhila Anil
DRUG DELIVERY SYSTEM (DDS) : M.PHARM
INTRODUCTION
FUNCTIONS OF PROTEINS AND PEPTIDES
MAIN BARRIERS OF EFFECTIVE ORAL DELIVERY
APPROACHES FOR ORAL DELIVERY OF DRUGS
Introduction to Anticoagulants
Coagulants, Local agents, Systemic agents, Anticoagulants, Heparin, Low molecular weight heparins, Heparinoids, Oral anticoagulants (Warfarin), Therapeutic uses
Presented by
N. Ramya
Department of Pharmacology
Proteins are the large organic compounds made of amino acids arranged in a linear chain and joined together by peptide bonds.
Protein > 50 amino acids
PEPTIDES: These are short polymers formed from the linking, in a defined order of amino acids.
peptide < 50 amino acids
Ethnobotany and Ethnopharmacology:
Ethnobotany in herbal drug evaluation,
Impact of Ethnobotany in traditional medicine,
New development in herbals,
Bio-prospecting tools for drug discovery,
Role of Ethnopharmacology in drug evaluation,
Reverse Pharmacology.
Read| The latest issue of The Challenger is here! We are thrilled to announce that our school paper has qualified for the NATIONAL SCHOOLS PRESS CONFERENCE (NSPC) 2024. Thank you for your unwavering support and trust. Dive into the stories that made us stand out!
The Indian economy is classified into different sectors to simplify the analysis and understanding of economic activities. For Class 10, it's essential to grasp the sectors of the Indian economy, understand their characteristics, and recognize their importance. This guide will provide detailed notes on the Sectors of the Indian Economy Class 10, using specific long-tail keywords to enhance comprehension.
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Bills have a main role in point of sale procedure. It will help to track sales, handling payments and giving receipts to customers. Bill splitting also has an important role in POS. For example, If some friends come together for dinner and if they want to divide the bill then it is possible by POS bill splitting. This slide will show how to split bills in odoo 17 POS.
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2024.06.01 Introducing a competency framework for languag learning materials ...Sandy Millin
http://sandymillin.wordpress.com/iateflwebinar2024
Published classroom materials form the basis of syllabuses, drive teacher professional development, and have a potentially huge influence on learners, teachers and education systems. All teachers also create their own materials, whether a few sentences on a blackboard, a highly-structured fully-realised online course, or anything in between. Despite this, the knowledge and skills needed to create effective language learning materials are rarely part of teacher training, and are mostly learnt by trial and error.
Knowledge and skills frameworks, generally called competency frameworks, for ELT teachers, trainers and managers have existed for a few years now. However, until I created one for my MA dissertation, there wasn’t one drawing together what we need to know and do to be able to effectively produce language learning materials.
This webinar will introduce you to my framework, highlighting the key competencies I identified from my research. It will also show how anybody involved in language teaching (any language, not just English!), teacher training, managing schools or developing language learning materials can benefit from using the framework.
Model Attribute Check Company Auto PropertyCeline George
In Odoo, the multi-company feature allows you to manage multiple companies within a single Odoo database instance. Each company can have its own configurations while still sharing common resources such as products, customers, and suppliers.
Operation “Blue Star” is the only event in the history of Independent India where the state went into war with its own people. Even after about 40 years it is not clear if it was culmination of states anger over people of the region, a political game of power or start of dictatorial chapter in the democratic setup.
The people of Punjab felt alienated from main stream due to denial of their just demands during a long democratic struggle since independence. As it happen all over the word, it led to militant struggle with great loss of lives of military, police and civilian personnel. Killing of Indira Gandhi and massacre of innocent Sikhs in Delhi and other India cities was also associated with this movement.
2. 2 INTRODUCTION
Proteins are the most abundant macromolecules
in the living cells, occurring in all cells and all parts
of cells.
Cells can produce proteins that have strikingly
different properties and activities, by joining same
20 amino acids in many different combinations and
sequences.
The term protein is used for molecules composed
of over 50 amino acids, and peptide for molecules
composed of less than 50 amino acids.
BY VISHAL SHARMA
3. 3
Scientific advances in molecular and cell biology have
resulted in the development of two new biotechnologies.
The first utilizes RECOMBINANT DNA to produce protein
products.
The second technology is HYBRIDOMA TECHNOLOGY.
Various proteins and peptides drugs are epidermal
growth factor, tissue plasminogen activator.
BY VISHAL SHARMA
4. 4 PROTEIN AND PEPTIDE DRUGS
Management of illness through medication is
entering a new era in which a growing number of
biotechnology produced peptide and protein drugs
are available for therapeutic use.
Ailments that can be treated effectively by this new
class of therapeutic agents include cancers, memory
impairment, mental disorders, hypertension.
BY VISHAL SHARMA
6. 6
MARKETED PEPTIDES IN READY TO USE
FORMULATIONS
Product Formulation Route Indication
Pitressin 8-Arginine i.m. s.c. Post operative
Vasopressin abdominal
distension
Lupron Leuprolide s.c. Prostatic cancer
Syntocinon Oxytocin i.m. i.v. Labour
induction
Sandostatin Octreotide s.c. Intestinal
tumour
Calcimar Salmon s.c. hypercalcemia
BY VISHAL calcitonin
SHARMA
7. 7
SUSTAINED RELEASE
DOSAGE FORMS
Product Formulation Route Indication
Lupron Leuprolide i.m. Prostatic
cancer
H.P.Acthar gel ACTH i.m. s.c. Antidiureti
c
Pitrressin tannate Vasopressin i.m. Endocrine
in oil tannate cancer
BY VISHAL SHARMA
8. 8 PROTEIN AND PEPTIDE DRUGS
They are therapeutically effective only by
parenteral route.
Repeated injections are required.
Therapeutic applications of these drugs rely on
successful development of viable delivery systems
to improve their stability and bioavailability.
BY VISHAL SHARMA
10. 10
NON PARENTERAL SYSTEMIC
DELIVERY / NON INVASIVE
These routes are useful for long term therapy.
Higher patience compliance (oral)
Reduction in administration cost
Without permeation enhancers lower bioavailability
is achieved when these routes are used.
Lower bioavailability is due to poor mucosal
permeability.
BY VISHAL SHARMA
12. 12 CHALLENGES
Large molecular size
Susceptibility to enz. Degradation
Short plasma half life
Ion permeability
Immunogenicity
Aggregation
Denaturation etc
BY VISHAL SHARMA
13. 13
ABSORPTION OF PROTIENS
FOLLOW
BY VISHAL SHARMA
14. 14 ABSORPTION MECHANISM
90% of nutrient absorb in small intestine.
P & P absorption is limited by acidic
environment , action of enz. ,non absorptive
nature of epithelial.
Through paracellular and transcellular mech.
They absorbed into blood or lymph (in villi)
BY VISHAL SHARMA
15. DEVELOPMENT OF DELIVERY
SYSTEMS FOR PEPTIDE AND
15
PROTEIN BASED
PHARMACEUTICALS
Considerations are to be given for following
aspects :
barriers to oral absorption
Preformulation and Formulation
considerations
Pharmacokinetic considerations
Analytical considerations
Regulatory considerations
BY VISHAL SHARMA
16. DEVELOPMENT OF DELIVERY
16 SYSTEMS FOR PEPTIDE AND
PROTEIN BASED
PHARMACEUTICALS
Considerations are to be given for following
aspects :
barriers to oral absorption
Preformulation and Formulation
considerations
Pharmacokinetic considerations
Analytical considerations
Regulatory considerations
BY VISHAL SHARMA
17. 17 BARRIERS TO ORAL ABSORPTION
Age related development of macromolecule permeability
barrier
Physical barrier - Size , charge ,solubility
Chemical barriers- pH solubility profile
Enz. Barriers
Interplay b/w P-glycoprotien & CYP3A4
BY VISHAL SHARMA
18. AGE RELATED DEVELOPMENT OF
MACROMOLECULE PERMEABILITY
18
BARRIER
It was found out that permeability of the
neonates intestine is good for the
macromolecules and as the age increases the
permeability was reduce for macro. Mol. & inc
for small molecules.
BY VISHAL SHARMA
19. 19 PHYSICAL BARRIER
Size ,charge and solubility is in our hand to change by
formulation and chemistry change.
For ex. Sustained release human insulin by attaching
with lipophilic molecule.
BY VISHAL SHARMA
20. 20
Surface adsorption :
Glass and plastic surfaces adsorbs proteins and
peptides.
To avoid surface adsorption albumin, gelatin, sodium
chloride can be used.
Aggregation behaviour :
To prevent aggregation additives are used such as :
urea, glycerol, EDTA, lysine, poloxamer 188.
BY VISHAL SHARMA
21. 21 CHEMICAL BARRIERS
pH :
Solution pH is important for stability
purpose. For simple peptides pH of minimum
degradation should be identified. Peptides
are usually formulated at slightly acidic pH
(3-5). For proteins pH is set away from
isoelectric pH to avoid aggregation.
Insulin is more stable at pH 5.4. However for
solubility reasons insulin injection pH are
2.5-3.5 or 7-7.8.
BY VISHAL SHARMA
22. 22
ENZ. BARRIERS/PROTEIN
INSTABILITIES
The degradation of proteins and peptides can
be divided into two main categories :
1. Those that involve a covalent bond.
2. Those involving a conformational change. This
process is often referred to as denaturation.
BY VISHAL SHARMA
23. 23 PEPTIDE FRAGMENTATION
The peptide bond (RNH-CO-R) is succeptible to
hydrolysis.
Peptide bonds are considered stable unless hydrolysis
is assisted by neighbouring group. Hydrolysis rate is
affected by solution pH.
DEAMIDATION
It means removal of ammonia from amide moiety.
Deamidation is the major factor for instability of insulin,
ACTH, Human Growth Hormone. In acidic media
peptides deamidate by direct hydrolysis.
BY VISHAL SHARMA
24. 24
OXIDATION
Sulphur containing amino acids are prone to oxidation.
MAILLARD REACTION
In the maillard reaction the carbonyl group (RCH=O) from
glucose can react with the free amino group in a pepide to
form a Schiff base. This reaction is acid catalysed.
DIMERISATION AND POLYMERIZATION
Insulin forms a small amount (about 1%) of covalent
dimer and polymer during two years cold storage.
Production of these species increases as temperature
increases.
BY VISHAL SHARMA
26. 26
PROTEASE INHIBITORS
Coadministration of protease inhibitors provides a
viable means to circumvent the enzymatic barrier in
achieving the delivery of peptide and protein drugs.
Th e choice of protease inhibitors will depend on the
structure of these therapeutic drugs, and the
information on the specifi city of proteases is essential
to guarantee the stability of the drugs in the GI tract.
A number of inhibitors including aprotinin (trypsin
/chymotrypsin inhibitor), amastatin, bestatin,
boroleucine, and puromycin (aminopeptidase
inhibitors) have been reported for this purpose
BY VISHAL SHARMA
27. 27
INTERPLAY B/W P-
GLYCOPROTIEN AND CYP3A4
P-gp is ABC transporter associated with MDR
CYP3A4 are enz.
BY VISHAL SHARMA
29. 29 PERMEATION ENHANCER
Without permeation enhancers lower
bioavailability is achieved when these routes are
used.
Lower bioavailability is due to poor mucosal
permeability.
Sodium tauroglycocholate is commonly used
penetration enhancer.
BY VISHAL SHARMA
30. DEVELOPMENT OF DELIVERY
30 SYSTEMS FOR PEPTIDE AND
PROTEIN BASED
PHARMACEUTICALS
Considerations are to be given for following
aspects :
barriers to oral absorption
Preformulation and Formulation
considerations
Pharmacokinetic considerations
Analytical considerations
Regulatory considerations
BY VISHAL SHARMA
31. PREFORMULATION AND
31 FORMULATION
CONSIDERATIONS
Denaturation stabilizers
Maximising oral protein and peptide absorption
Chemical Modifications
Amino acid Modification
Hydrophobization
Conjugation with polymers
BY VISHAL SHARMA
32. 32
DENATURATION
o Specific confirmation is required for proteins to exert
pharmacological and physiological activities.
Denaturation is a process of altering protein
confirmation. Heat, organic solvents, high salt
concentration, lyophilization can denature proteins.
Protein confirmation refers to the specific tertiary
structure, which is determined by the primary and
secondary structures and the disulfide bonds and is held
together by three forces : hydrogen bonding, salt
bridges, and hydrophobic interactions.
BY VISHAL SHARMA
33. 33 COMMON STABILIZERS
SERUM ALBUMIN :
It can withstand heating to 60o C for 10 hours.
At pH 2 albumin molecule expands and elongates but
can return to native confirmation reversibly. Also, it
shows good solubility.
BY VISHAL SHARMA
34. 34
AMINO ACIDS
Glycine is most commonly used stabilizer.
Mechanism of action of amino acids as stabilizers may
be one of the following :
Reduce surface adsorption.
Inhibit aggregate formation.
Stabilize proteins against heat denaturation.
BY VISHAL SHARMA
35. 35
SURFACTANTS
They cause denaturation of proteins by hydrophobic
disruption. However judicious use of surfactants can
protect proteins from other denaturants. Proteins have
tendency to concentrate at liquid/liquid or liquid/air
interface. Due to this proteins may adopt non native
confirmation and such confirmation is having less
solubility.
Optimal concentration of surfactants for stabilization
should be greater than cmc. Ionic surfactants are more
effective stabilizers than non ionic surfactants.
Various surfactants used are : poloxamer 188,
polysorbate.
BY VISHAL SHARMA
36. 36
POLYHYDRIC ALCOHOLS AND
CARBOHYDRATES :
They contain –CHOH-CHOH- groups which are
responsible for stabilizing proteins. They stabilize
proteins against denaturation caused by elevated
temperature or by freeze drying or by freeze thaw
cycles.
Many important therapeutic proteins and peptides are
derived from blood such as immune globulin,
coagulation factors. For viral destruction
pasteurization at 60o C for 10 hours is needed. Hence
thermal stability is needed. Long chain polyhydric
alcohols are more effective as stabilizers. e.g. sorbitol,
xylitol.
BY VISHAL SHARMA
37. 37
Mechanism of action as stabilizers for polyhydric
alcohols is that they have effect on structure of
surrounding water molecules which strengthens
hydrophobic interactions in protein molecules.
Mechanism of action as stabilizers for carbohydrates is
that they provide dry network that provides significant
support for protection.
Polyhydric alcohols used are sorbitol, mannitol, glycerol,
PEG.
Carbohydrates used are glucose, mannose, sucrose,
ribose.
BY VISHAL SHARMA
38. 38
ANTI-OXIDANTS
Thiol compounds such as thioacetic acid, triethanolamine, reduced
glutathione and metal chelants such as EDTA are used as
antioxidants.
MISCELLANEOUS
Certain enzymes can be stabilized by using compounds having
similar structures of enzymes. e.g. Glucose stabilizes
glucoamylase while aspargine stabilizes asparginase.
Compounds forming stable complex through ionic interaction
with proteins can stabilize proteins.
Calcium is essential for thermal stability of certain amylases or
proteases. SHARMA
BY VISHAL
39. MAXIMISING ORAL PROTEIN
39 AND PEPTIDE ABSORPTION
1. Amino acid modifications
Metkephamid, an analog of methionine
enkephalinwith 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.
BY VISHAL SHARMA
40. 40
2. Hydrophobization
Hydrophobization of peptides may be attempted by
two approaches. The first ispeptide backbone
modification to include more of hydrophobic amino
acids; the second would be covalent conjugation of a
hydrophobic moiety—for example, a lipid
orpolymeric tail.
Increasing the hydrophobicity of a peptide or protein by
surface modification using lipophilic moieties may be of
particular benefit to transcellular passive or active
absorption by membrane penetration or attachment,
respectively; or it may simply aid in the increased
stability of the protein.
BY VISHAL SHARMA
41. 41
EXAMPLE
lipophilic modificationof 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.
BY VISHAL SHARMA
42. 42 CONJUGATION WITH POLYMER
One of the most commenly used technique is
(PEG)-ylation technology.
Enlarges the active molecule by attaching a
web like shield of hydrated PEG polymer chain
around the molecule.
BY VISHAL SHARMA
43. 43
BENEFITS
increase clearance half life
Provide possibility of drug to stay more in the
circulation.
Increase molecular stability
Change the vol. of distribution
Reduce immune response
BY VISHAL SHARMA
44. DEVELOPMENT OF DELIVERY
44 SYSTEMS FOR PEPTIDE AND
PROTEIN BASED
PHARMACEUTICALS
Considerations are to be given for following
aspects :
barriers to oral absorption
Preformulation and Formulation
considerations
Pharmacokinetic considerations
Analytical considerations
Regulatory considerations
BY VISHAL SHARMA
45. 45
PHARMACOKINETIC
CONSIDERATIONS
Basal insulin secretion in healthy subjects
shows circadian rhythm with peak time at
15:00 hrs.
It has been suggested that larger amount of
insulin is needed in afternoon and night.
Hence delivery systems could be designed by
considering such aspects.
BY VISHAL SHARMA
46. DEVELOPMENT OF DELIVERY
46 SYSTEMS FOR PEPTIDE AND
PROTEIN BASED
PHARMACEUTICALS
Considerations are to be given for following
aspects :
barriers to oral absorption
Preformulation and Formulation
considerations
Pharmacokinetic considerations
Analytical considerations
Regulatory considerations
BY VISHAL SHARMA
47. 47 ANALYTICAL CONSIDERATIONS
Many tests are required for stability of protein
products to assure identity, purity, potency and
stability of formulation.
Due to complexity of proteins bioassay are
required to assess potency of the formulation.
Bioassay are of two types : in vitro and in vivo.
In case of in vitro bioassays response of cells to
hormones and growth factors is monitored. In case
of in vivo bioassay pharmacological response of
animals to proteins is monitored : e.g., post
injection blood sugar in rabbits is monitored for
bioassay of insulin.
BY VISHAL SHARMA
48. 48 U.V. SPECTROSCOPY
Proteins containing aromatic amino acid residues
such as phenyl alanine, tyrosine, tryptophan can be
detected by u.v. spectroscopy.
Ultraviolet spectroscopy can be used for in process
quality control.
Protein aggregates scatter u.v. light and absorbance
increases. Hence u.v. spectroscopy can be used to
monitor protein aggregation.
BY VISHAL SHARMA
49. 49
BRADFORD ASSAY :
This assay employs the principle that in the presence of
proteins absorption maximum of coomassie brilliant blue dye
changes from 465nm to 595nm.
BIURET TEST :
Structure of biuret and proteins are similar. Biuret in presence
of proteins or peptides reduces copper to cuprous ions in
alkaline solutions and colour complex is developed.
BY VISHAL SHARMA
50. 50 THERMAL ANALYSIS
Differential scanning calorimetry (DSC) is
gaining widespread use as a tool for
investigating transitions of confirmation as a
function of temperature and, more
importantly, the effect of potential stabilizing
excipients in a protein solution. The apex of
the endothermic peak is the transition
temperature between native and partially
unfolded confirmations.
BY VISHAL SHARMA
51. 51 ELECTROPHORESIS
Most often used technique for protein products is
sodium dodecyl sulphate polyacrylamide gel
electrophoresis (SDS-PAGE).
Proteins are denatured by boiling in the SDS solution.
All charges of protein are masked by negative charge
of dodecyl sulphate.
Thus protein moves on polyacrylamide gel strictly on
basis of size of protein molecule.
This technique is useful for determining molecular
weight of proteins.
For visualization of proteins on the gel reagents used
areBYsilver nitrate, coomassie brilliant blue dye.
VISHAL SHARMA
52. 52
LIQUID CHROMATOGRAPHY
To study stability of proteins and peptides HPLC
is useful technique. Various modes used are
Normal Phase HPLC
Reverse Phase HPLC
Ion Exchange
Chromatofocusing
BY VISHAL SHARMA
53. DEVELOPMENT OF DELIVERY
53 SYSTEMS FOR PEPTIDE AND
PROTEIN BASED
PHARMACEUTICALS
Considerations are to be given for following
aspects :
barriers to oral absorption
Preformulation and Formulation
considerations
Pharmacokinetic considerations
Analytical considerations
Regulatory considerations
BY VISHAL SHARMA
54. 54 REGULATORY CONSIDERATIONS
Four federal agencies regulates biotechnology
products :
1. US Food and drugs administration (USFDA)
2. Environmental protection agency (EPA)
3. Occupational safety and health administration
(OSHA)
4. US Department of agriculture (USDA)
BY VISHAL SHARMA
55. 55
Nasal route :
Poor permeability is common problem.
Proteolytic enzymes in nasal mucosa degrades the
administered drugs.
Pulmonary route :
Monodisperse aerosol with a mass median aerodynamic
diameter of 3 µm was reported to achieve alveolar
deposition of 50% or more drug.
BY VISHAL SHARMA
56. 56
Ocular route :
Ocular absorption can be enhanced by use of
nanoparticles, liposomes, gels, ocular inserts.
Buccal route :
Mucoadhesive dosage forms can be used.
Rectal route :
solid dispersion of insulin with mannitol can produce
rapid release of insulin from suppositories.
BY VISHAL SHARMA
57. 57
Transdermal route :
Skin has very low proteolytic activity.
Two types of iontophoresis are used :
DIRECT CURRENT MODE
PULSE CURRENT MODE
Vaginal route :
Especially useful to deliver hormones.
Not much accepted in developing countries.
BY VISHAL SHARMA
58. 58 PARENTERAL ROUTE
Most efficient route.
Extremely short duration of action.
Hence, viable drug delivery techniques are to
be developed such as controlled drug delivery
systems for prolongation of biological activity.
Complications arising from this route are :
Thrombophlebitis
Tissue necrosis
immunogenicity
BY VISHAL SHARMA
59. 59 PARENTERAL ROUTE
BIO DEGRADABLE POLYMERS BASED DRUG
DELIVERY SYSTEMS :
Microspheres are used as drug carriers which
are made of natural or synthetic polymers.
Natural polymers have advantage that they are
biocompatible and inexpensive. But they are
lacking purity. Synthetic polymers are PLA,
PGA, PLGA.
Mechanism of degradation are : firstly random
chain scission occurs. Then soluble oligomeric
products are formed which then gets
converted to soluble monomers.
BY VISHAL SHARMA
60. 60 Cont……………
PLGA biodegrades into lactic and glycolic
acids. These acids enter into TCA cycle and
then eliminated as carbon dioxide and water.
Injectable controlled release formulations of
certain drugs are formulated using
lactide/glycolide copolymers. Such drugs are
LHRH, calcitonin, insulin.
Nanoparticles made of PLGA, albumin
polystyrene have potential for targeted drug
delivery.
BY VISHAL SHARMA
61. 61
LIPOSOMES BASED DRUG
DELIVERY SYSTEMS
Liposomes are microscopic vesicles composed
of one or more lipid layers that enclose
aqueous compartments. Liposome membranes
are semi permeable and can thus be used as
controlled release systems. Liver is natural
target for liposomes.
Disadvantage is low stability of liposomes.
BY VISHAL SHARMA
62. 62
HYDROGEL BASED DRUG
DELIVERY SYSTEMS
Hydrogels have advantage of biocompatibility.
Insulin has been incorporated into hydrogels and
widely investigated.
Emulsions , multiple emulsions, micro emulsions,
resealed erythrocytes can also be used to deliver
protein and peptide drugs.
BY VISHAL SHARMA
63. 63 APPLICATIONS
Oral peptides today
Nasal delivery of proteins
Pulmonary delivery of proteins
Polymeric protein delivery to increaser half life
Sustained release peptide systems
Chemical altered protiens
BY VISHAL SHARMA
64. 64 ORAL PEPTIDES TODAY
Desmopressin acetate (DDAVP) is a synthetic analogue of
8 arginine vasopressin: ant diuretic hormone. Marketd by
aventis pharmaceutical and is approved for diabetes
insipidus.0.16 % bioavilable
Novartis and roche pharmaceutical market cyclosporin
(small lyophilic mol. For graft rej.) 30% bioavailibilty
BY VISHAL SHARMA
65. 65 NASAL DELIVERY OF PROTIEN
Brand company drug Used for bioavailibi
name lity
Miacalcin® Novartis Calcitonin osteoporosi 3%
analogue s
Synarel® Hoffman la- LHRH endometros 2.8%
roche agonist is
naferlin
DDAVP Vasopressi Diabetes 3%
n analogue insipidus
BY VISHAL SHARMA
66. 66
PULMONARY DELIVERY OF
PEPTIDE
Various companies like Nektar , Alkermes ,
Aradigm have developed arosolised insulin
showing about 10% bio available as compared to
SC.
Particle size in important in transfer of molecule
from pulmonary.
Size of insulin should be 0.5-3 micron.
See figure back side
BY VISHAL SHARMA
68. 68 POLYMERIC PROTEINS
Sustained release protien
LHRH agonist goserelin with PLGA marketd by
AstraZeneca : administer SC 14-16 gauge needle.
Octreotide LAR (long acting release) by novartis
for gastroentopancreatic endocrine tumors.
Neutropin Depot® by Alkermes and Genetech ;
human growth hormones.
BY VISHAL SHARMA
69. 69
CHEMICALLY ALTERED
PROTEINS
Prepared by PEGylation
First PGA product FDA approved was Enzon’s Adagen®
(bovine enx. Adenosine deaminase) For ADA def. severe
combined disease.
Another its product was Oncasper® (l-as.paragenase)
AMINO ACID SUBSTITUTION
Rapid insulin Eli-Lilly ; lys pro insulin is an ex.
BY VISHAL SHARMA
70. 70 CONCLUSION
Protein and peptide based pharmaceuticals are
rapidly becoming a very important class of
therapeutic agents and are likely to replace many
existing organic based pharmaceuticals in the very
near future.
Peptide and protein drugs will be produced on a
large scale by biotechnology processes and will
become commercially available for therapeutic use.
BY VISHAL SHARMA
71. 71
REFERENCES
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pharmaceutical chemistry. 11 th ed. Philadelphia : Lippincott Williams and
wilkins; 2005.p.851-852.
BY VISHAL SHARMA
72. 72
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livingstone; 2003.p.386-388.
BY VISHAL SHARMA
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BY VISHAL SHARMA