Different novel routes of insulin delivery

1. Presented By,
Mr. Chavan saurav Rajendra
Roll no. 102
First Year M. pharm (pharmaceutics)
Semester - I
STES’s Smt . Kashibai Navle College of Pharmacy Kondhwa
(BK) Pune -411048
Guided by,
Dr. (Mrs). Meera C. Singh
(M.pharm ,PHD)
Associate professor and HOD
Department of Pharmaceutics
TOPIC
Case study of marketed drug delivery systems of insulin
1

2. Content-
1) Introduction
2) Insulin therapy
3) Applications of insulin as a drug
4) Different types of insulin drug delivery systems
5) Different devices used in insulin drug delivery as injections
6) Marketed examples
7) Case study
8) Future prospects
9) References
2

3. Introduction:
What Is Insulin?
●Insulin is a hormone created by pancreas that controls the amount of
glucose in your bloodstream at any given moment. It also helps store glucose
in your liver, fat, and muscles. Finally, it regulates your body’s metabolism of
carbohydrates, fats, and proteins.
●It is made by the beta cells of the pancreas and
released into the blood when the glucose level
goes up, after eating.
●Insulin helps glucose to in enter the body's
cells, where it can be used for energy or stored
for future use.
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4. History of insulin:-
• In 1869, the German medical student Paul Langerhans discovered clusters of cells in
the pancreas that he called "islets of Langerhans”.
• In 1901, the American physiologist Eugene Opie observed that the islets of Langerhans
contained two distinct types of cells: alpha cells, which produced glucagon, and beta
cells, which produced an unknown substance that seemed to regulate glucose
metabolism.
• In 1920, the Canadian scientist Frederick Banting and his assistant Charles Best
conducted experiments in dogs that led them to discover insulin.
• They found that by extracting secretions from the pancreas of healthy dogs and
injecting them into dogs with diabetes
• In 1923, the pharmaceutical company Eli Lilly began producing insulin in the United
States.
• Banting and Macleod, who had provided laboratory space and scientific guidance, were
awarded the Nobel Prize in Physiology or Medicine in 1923 for their discovery of
insulin. 4

5. Limitation for oral insulin delivery:-
●When insulin is delivered orally, it is broken down by the digestive system before it can
reach the bloodstream.
●Insulin is a protein hormone, and like all proteins, it is broken down by the digestive
enzymes in the stomach and small intestine into smaller peptide fragments and amino
acids.
●As a result, oral delivery of insulin is not effective in controlling blood sugar levels in
people with diabetes.
Limitations:-
1) proteolytic degradation
2) Low bioavailability
3) Inconsistent absorption
4) Need of large Dosage
5) Safety concern
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6. Insulin Therapy:-
●Insulin was isolated in 1921 with its first clinical use in
1922. It was extracted by Banting & Best. Insulin is a two
chain polypeptide having 51 amino acids. The A-chain has
21 while B-chain has 30 amino acids joined together by
Disulfide brides.
● Insulin has an isoelectric point of 5.3,charge -2 to -6 in
pH range 7-11.The conventional form of insulin delivery is
through subcutaneous injections and average
hyperglycemic patient takes 3-4 times insulin injection per
day.
● Insulin is measured in IU. One international unit of
insulin (1 IU) is defined as the "biological equivalent" of
34.7 μg pure crystalline insulin.
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7. Applications of insulin as a drug:-
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8. • Different types of insulin drug delivery system:
1) Nasal delivery
2) Transdermal delivery
3) Buccal delivery
4) Ocular delivery
5) Rectal delivery
6) Inhaled delivery
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9. 9

10. 1) Nasal Delivery:-
• Nasal cavity has large surface area (150
Sq. cm.)
• Epithelial surface is covered with
numerous microvilli, hence absorption is
greater and also avoiding loss of insulin
from first pass hepatic metabolism.
• Examples of Preparations-A)Nasulin™
by CPEX Pharmaceuticals & by Nastech
Pharmaceuticals.
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11. 2)Transdermal Delivery:-
●A transdermal patch is a medicated adhesive patch that is
placed on the skin to deliver a specific dose of medication
through the skin and into the bloodstream.
● Microneedles (MNS) have been widely studied for
transdermal delivery of insulin as minimally invasive and
painless in human subjects.
●Examples of Preparations- A)Pectin insulin containing
dermal patches-prepared by dissolving pectin/insulin in
deionised water & solidified with CaCl2.
B)U-Strip-contain up to 100 units of insulin.
C)Transferosomal gels
D) Insulin emulgel
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12. 3)Buccal Delivery:-
●The drug is delivered through an aerosol spray into the
oral cavity.
●The molecules absorbed via. The buccal route enter
the internal jugular vein and reaches the systemic
circulation by passing hepatic first pass metabolism.
●Absorption enhancers-surfactants, bile salts, chelators,
SLS, HPMC, Carbopol 934 Polysorbate 80, Sorbitol.
●Examples of Formulation-A)Oral-lyn-developed by
Generex Biotechnology Corporation(Toronto, Canada).
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13. 4)Ocular Delivery:-
●The rate of absorption was seen fast in the ocular route than the injection.
●ocular insulin delivery system is a method of delivering insulin directly to the eye to treat
diabetic retinopathy, a complication of diabetes that affects the eyes.
●ocular insulin delivery involves the use of specialized techniques to transport insulin
molecules across the BRB and target specific cells within the retina, where insulin can
activate its receptor and exert its therapeutic effects.
●Delivered by the use of nanoparticles ,liposomes ,ocular inserts & gels.
●Advantages: less side effects & avoidance of hepatic first pass metabolism.
●Limitations: low bioavailability and irritation & loss of drug molecules via. blinking,
tearing
● Enhancers:saponin,dodecylmaltoside,tetradecylmaltoside,fusidicacid.
●GELFOAM an absorbable gelatin sponge ocular devices have been developed as insulin
carriers for systemic administration of insulin.
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14. 5) Rectal delivery:-
●This system involves inserting a suppository or an enema
containing insulin into the rectum, where it is absorbed through the
rectal mucosa.
●The technique to improve rectal absorption is by creating an
adhesive interaction between, the delivery system & rectal mucosa
,increasing drug residence time at the absorption sites.
●Suppositories containing 100 U insulin & 200 mg Sodium
Salicylate as an absorption enhancer were tested in humans.
Hypoglycemic effects were achieved in 15 mins. & lasted upto 90
mins. Post administration.
●Also available Rectal Gels (Pluronic F-127 gel).
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15. 6) Inhaled Delivery:-
● Inhaled drugs are absorbed into the alveolar capillary
network, which has advantage of having large surface area(100
Sq. In.) and thin diffusion barrier.
●Advantages: Vast and well perfused absorptive surface,
absence of certain peptidases that are present in GIT ,Faster
onset of action.
●Absorption Enhancers: Cyclodextrin(CD) derivatives
liketetradecyl-ß-maltoside (TDM), dimethyl-B-
cyclodextrin(DMBCD) & hydroxypropyl-B-cyclodextrin
(HPBCD).
●Examples of Preparations:a) Exubera-first USFDA approved
human insulin in powder form, developed by Pfizer pharma &
Sanofi Aventis. b)Afrezza- by Mankind & Sanofi.c)AERx- by
Novo Nordisk, a world leader in insulin manufacture and
diabetes care. 15

16. Different devices used in insulin delivery as injections :-
1) Insulin pen device
2) insulin jet injector
3) insulin prefilled syringes
4) insulin pump
5)vial and syringe
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17. 1) Insulin Pen Device:-
• The first insulin pen (NOVOPEN®) was introduced
byNova Nor Disk in 1987.
• Two types of insulin pens: Prefilled insulin pen
device & Reusable insulin pen device.
• In using insulin pens, the patient must attach a
needle,prime the pen, set the dose by a dial and
depresses the plunger to administer the selected dose.
• The needles for pens are available in varying lenghts
(from 8mm to 12.7mm) and varying gauges (from 29
to 31 guages).
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18. 2) Insulin Jet Injectors:-
• Jet injectors (introduced in 1980) are designed
to deliver a fine stream of insulin
transcutaneously at high speed & high
pressure to penetrate the skin without a
needle.
• The available jet injectors allow a dose range
of 2 to 50 units of insulin.
• Insulin jet injectors decrease the chance of
subcutaneous infection.It is mainly used in
patients with Needle Phobia.
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19. 3) Insulin Prefilled syringes:-
●Prefilled disposal syringes Contain specific type or
Mixture Of regular and Modified Insulin.
4) Insulin Pumps:-
●An insulin pump is a small computerized device.
It delivers insulin through a thin tube that goes
under your skin Subcutaneously.
●The first pump was introduced in market in
1974. .
The insulin pumps has three parts i.e. a reservoir
filled with insulin, pump operated on battery and
computer chip that allows the patient in
controlling insulin delivery.
●The insulin reservoir is connected
subcutaneously and changed every 2 or 3 days. 19

20. 5)Vial and syringe:-
• In 1924, 2 years after the discovery of insulin,
Becton, Dickinson and Company (BD) made
a syringe specifically designed for the insulin
injection.
• Initial syringes were made of metals and/or
glass, reusable and required boiling after each
use to sterilize
• Despite all these advances, many patients do
not feel to inject insulin 3-4 times a day as a
result of needle phobia.
• Insulin syringes with three different needle
lengths 6, 8 and 12.7 mm are available.
• Also, three gauge sizes, 31, 30 and 29 are
available
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21. Marketed examples :-
Sr no Types of insulin delivery Marketed examples
1 Nasal delivery Nasulin
2 Transdermal delivery U-strip
3 Buccal delivery Oral-lyn
4 Ocular delivery Gelfoam (pfizer)
5 Rectal delivery Pluronic f127 gel (allvei)
6 Inhaled delivery Afrezza Insulin inhaler (Mankind
and sanofi)
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22. Sr no Device’s of insulin
delivery
Marketed examples
1) Insulin pen device Novopen
2) Insulin jet injectors Insujet
3) Insulin prefilled syringe Semglee
4) Insulin pump Medtronic
5) Vial and syringe Humulin
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23. Case study Of Recosulin R
• Product name :- Recosulin R
• Manufacturer/marketer:- Shreya life
sciences pvt.Ltd
• Recosulin R 40IU/ml Injection is a short-
acting insulin used to treat type 1 and type 2
diabetes mellitus. It is used together with a
healthy diet and regular exercise to control
blood sugar levels after meals.
• This helps to prevent serious complications
of diabetes like kidney damage and
blindness
• Dosage: 40 IU/ML
• Route of administration- Injection
(subcutaneously).
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24. ●Mechanism of action:-
short-acting insulin, which starts working within 30
minutes after injection. It works similar to the insulin
produced by the body. Insulin facilitates reuptake of
sugar in muscle and fat cells and also suppresses the
production of sugar in the liver.
●This product contains recombinant human mono-
component Insulin
●The most common side effect of this Medicine Is
hypoglycemia, To prevent this always inject correct
dose.
●Storage condition :- Store in a refrigerator (2 - 8°C).
Do not freeze.
●Direction:- shake gently before use
●price:-₹140
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25. Case study of Afrezza®
• Product name:- Afrezza®
• Manufacturer/marketer:- MannKind Corporation
• Unlike traditional insulin injections, Afrezza is a
powder that is inhaled into the lungs before meals
using a small, handheld inhaler device.
• It works by delivering insulin directly to the
bloodstream through the lungs, which allows for
more rapid and efficient absorption into the body.
• Storage condition:- stored at 36° F to 77° F (2° C
to 25°) and protect from heat and light
• Dosage:-Available as single-use cartridges, 4
units/cartridge,8 units/cartridge,12units/cartridges.
• Route of administration:- nasal route(via inhaler)
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26. • Mechanism of action:-
• insulin in the powder is absorbed into the
bloodstream through the lungs. .
• Once in the bloodstream, the insulin binds to
insulin receptors on the surface of cells
throughout the body
• The binding of insulin to its receptors triggers a
series of molecular signals inside the cell that
leads lowers the level of glucose in the
bloodstream
• The most common side effects of Afrezza Is
hypoglycemia, This happens on overdosing.
• Afrezza is firstly launched in united States in
year 2015
• Price.:-₹155/cartridge (₹27964 for 180 cartridge
box) 26

27. Future prospect’s:-
• several promising future prospects for insulin drug delivery. Here are some of the
potential developments
1)Smart Insulin Delivery Devices:
Smart insulin delivery devices use glucose-responsive materials that release insulin
in response to changes in blood sugar levels. These devices could provide a more
precise and convenient way of delivering insulin, reducing the risk of hypoglycemia
and improving overall diabetes management.
2)Implantable Insulin Pumps: Insulin drug delivery has undergone significant
advancements in recent years.
• Implantable insulin pumps are small devices that can be surgically implanted
under the skin and deliver insulin directly into the bloodstream. These pumps offer
a more discreet and convenient way of delivering insulin, eliminating the need for
frequent injections.
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28. 3)Nanotechnology:
• Nanoparticle-based insulin delivery systems could offer more targeted and
efficient delivery of insulin. These systems use tiny particles to deliver insulin
directly to the cells that need it, reducing the risk of insulin resistance and
improving overall diabetes management.
4)Oral Insulin:
• Oral insulin is a type of insulin that can be taken as a pill rather than through
injection. While this technology is still in the early stages of development, it has
the potential to revolutionize insulin delivery and make diabetes management
easier and more convenient for millions of people.
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29. References:-
1) Rima B. shah, Manhar Patel, David M. Maahs, Viral M. shah. Insulin delivery
Methods: past, Present and future. 2016 Jan 2016 International. Journal of
pharmaceutical investigation, Jan 2016, Vol 6, page no 2-6.
2) Varshney H.M., Rajnish kumar, shailendra Mohan,Novel approches for insulin
delivery: current Status. International Journal of therapeutic Applications, volt
2012, Vo17, page Mo 26-30.
3) Amish Panchal, viral shah, U.M. Upadhyay. insulin drug delivery systems: A
review. International Journal of Research in pharmaceutical Sciences, 2011, vol 4
page No:- 486-490.
4) Garima sharma, Ashish Ranjan sharma, Ju-suk Nam, George panja priya C.Doss,
Sang-Soo Lee. Manoparticle based insulin delivery system: the next generation
based efficient therapy for Type 1 diabetes. Journal of nanobiotehnology, 2015,
page No 4-6.
5) Daniel A. Domingo-lopez, Giulia lattanzi, Lucien H.J. Eimear J. Wallace, Robert
Wylie, Janice o'sullivant- Eimear B. Dolah, Garry P. Duffy. Medical devices, smart
drug delivery, wearables & technology for treatment of Diabetes Melitus,
ELSEVIER advance drug delivery review,2022,page no:-5-9
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30. 6) Yung-chiles, Pahala simmamora, sivat pinsuwan, Samuel H yalkowsky. Review
on the systemic delivery of insulin via the ocular route. International Journal of
pharmaceutics, Feb 2002,vol 233, Page no 1-9
7) Al-Tabakha Mm and Arida Ai, Indian Journal of Pharmaceutical Science, “Recent
challenges in insulin delivery systems: A review” Volume 70, Issue 3, 2008, page no
278-286
8) KD Tripathi;Essentials of Medical Pharmacology; Ed. 7th 2013; Jaypee Brothers
Medical Publishers (P) Ltd; p.269-270.
9) M.Frier and Mark W. J Strachan. Insulin therapy: A Pocket Guide, london
Springer,2013. Page no:-51-57
10) https://www.shreya.co.in/
11) https://afrezza.com/about-afrezza/
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