RECENT TRENDS IN INSULIN DRUG

DELIVERY SYSTEM
T. N. Saifullah Sulaiman
Laboratorium Teknologi Formulasi
Fakultas Farmasi UGM
Traditional insulin drug delivery:
 Insulin therapy via subcutaneous or other parenteral route in diabetic patient
is preferred but on continuous administration there may be chance of
peripheral hyperinsulinemia, formation of thrombus, inflammation &
irritation at the site.

 Also patient suffering from needle phobia hesitate to take it.

 Historical background of painless insulin drug delivery system: This

technology was first described in 19th century in France, when the company
H Galante-manufactured an ‘Apparatus for Aqua puncture’. Since then, the
demand had increases considerably. It was first commercialized in the US in
1960’s. Biojet had summed up the reason for it in their brochure stating”
Patients hate needles, healthcare professionals fear accidental needle stick
injuries ,drug companies are looking for new and innovative ways of
delivering their products”.
 NEEDLE FREE TECHNOLOGY:
Needle free insulin injection provides following advantages:

i. Improve concordance with insulin regiment.

ii. Improve the patient health/well-being.
iii. Eliminates the need for sharp disposal and avoids needle stick injuries.
IV .Emotional benefits of using a needle free devices.
v. Fast injection, insulin is delivered in less than 0.3 seconds, regardless of
dose.
vi. No additional pressure required to delivered large doses.

 Additional benefits: Very fast injection compared with conventional needle

and no needle disposal issue.
 Organisations such as W.H.O. and C.D.C. (center for disease control)
support the development of needle free insulin drug delivery.
Jet injectors:
 A jet injector is a type of medical injecting syringe that uses a
high-pressure narrow jet of the injection liquid instead of a
hypodermic needle to penetrate the epidermis.
 It is powered by compressed air or gas, either by a pressure hose
from a large cylinder, or from a built-in gas cartridge or small
cylinder.
 Some are multi-shot, and some are one-shot. They are used by
diabetics to inject insulin as an alternative to needle syringes,
though they are still not very common.
Inhalable insulin
 Inhalable insulin was available from September 2006 to October 2007
in the United States as a new method of delivering insulin, a drug used
in the treatment of diabetes to the body.

 Insulin has poor oral absorption it can be better absorbed through

nasal mucosa

 Inhaled insulin appears to be a non-invasive, well-tolerated and liked

modality of treatment with potential for both type 1 and type 2
diabetes.
Exubera® insulin inhaler with insulin blisters and the inhaler's insulin
release unit (bottom left). The device is closed (left) for portability and
extended (right) before use (Pfizer).
AERx® insulin diabetes management system is an electromechanical device that delivers
insulin from solution at correct rate and depth of breathing (Novo Nordisk). The device has
capabilities of dosing increments by single-unit and data capture
 Insulin spray
 The buccal route is another promising alternative for insulin delivery. With the buccal
area having an abundant blood supply, it offers some advantages such as a means to
deliver the acid labile insulin, and elimination of insulin destruction by first pass
metabolism.

 The buccal spray formulation being developed by Generex Biotechnology, based in

Toronto, delivers insulin to the buccal cavity as a fine spray using company's 'rapidmist'
device.

 The patient does not inhale with the buccal spray device; instead, the drug is sprayed
onto the buccal mucosa.

 The high-speed spray allows the drug to be rapidly absorbed into the bloodstream.
 Other Buccal Insulin
 Gels
 Films
 Patches
 Buccoadhesive tablets
 Vesicles/Transferosomes
 nanopartices (pelleted bioadhesive nanoparticles)
 Sponges: are highly porous, flexible mucoadhesive devices
 Insulin Pen
In using insulin pens, the patient must attach a needle, prime the pain, set
the dose by a dial and depress the plunger to administer the selected dose.

There are two pen systems:

1. A replaceable cartridge pen reuses the pen portion. When the insulin is
empty, the vial is replaced by inserting a new one.
2. A prefilled pen is entirely disposable. When the insulin is gone, the
entire unit is discarded.
Pens with Replaceable Cartridges
 A replaceable cartridge pen reuses the pen portion. When the
insulin is empty, the vial is replaced by inserting a new one.

 Insulin cartridges for pens come in 3.0 ml and 1.5 ml sizes, with
3.0 being the predominant size.
Prefilled Pens
 A prefilled pen is entirely disposable. When the insulin is gone, the
entire unit is discarded

A Pen with Memory

In February, 2007, Eli Lilly announced a new concept to the US
market: “HumaPen MEMOIR is the first and only insulin pen with a
memory.
HumaPen MEMOIR records the date, time, and amount of your last
16 doses (including priming doses).
Insulin Micro Pumps
 The insulin pump delivers a single type of fast-acting insulin
in two ways:
i. Bolus dose that is pumped to cover food eaten or to correct a
high blood glucose level.
ii. Basal dose that is pumped continuously at an adjustable basal
rate to deliver insulin needed between meals and at night.
 Insulin Port
 An insulin port functions as a medication delivery channel directly into the
subcutaneous tissue.

 When applying the injection port, an insertion needle guides a soft cannula
(a small, flexible tube) under the skin. Once applied, the insertion needle is
removed and only the soft cannula remains below the skin, acting as the
gateway into the subcutaneous tissue.

 To inject through insulin port the needle of a syringe or insulin pen is used.
The needle remains above the surface of the skin, while the medication is
immediately delivered through the soft cannula and into the subcutaneous
tissue.
Transdermal Patch
 The Altea Therapeutics Passport System was the first product in development
shown in US FDA clinical trials to provide a non-invasive, controllable and
efficient way to deliver insulin via a patch on the skin.

 The insulin transdermal patch maintains constant basal levels while avoiding
skin depots of insulin common with subcutaneous injections.

 As a safety feature, if a patient begins to experience the hypoglycemia

associated with an inadvertent overdose of insulin, they may simply remove the
insulin transdermal patch, thus immediately ending the influx of insulin.
Insulin Pill
 Azopolymer coated pellets to deliver insulin to the colon region were
studied earlier.

 The azopolymer protects the entrapped therapeutic agent till the pellets
reach the colon. As only the bacteria inhabiting the colon secrete enzymes
that can breakdown the azopolymer, insu lin release will be initiated once the
pellets reach the large intestine.

 Microencapsulation of insulin in polymeric microspheres coated with pH

responsive polymers such as alginate is also known. Alginate coating protects
the spheres in the acidic pH of the stomach but dissolves in the intestine
where the pH increases to above 7 and liberates the entrapped insulin.
Insulin Capsule ?
Rectal gels

The rectal gels consisted of emulsion systems prepared from

pH 8 buffer solution containing insulin, an oleaginous phase,
a surface active agent and a viscosity increasing agent

rectal gel was tested in rabbits both in a parallel and a

crossover design in nondiabetic and diabetic animals
Insulin Suppositories
 Oramed pharmaceuticals, a developer of alternative drug
delivery system are conducting phase IA trials on eight healthy
human volunteer for ORMD 0802, companys newly developed
suppository

 Phase IA trials on its insulin suppositories mark an important

step in history of insulin delivery as it will provide a painless
option for diabetic who seek an alternative to current delivery
methods
Insulin Toothpastes
 GenoMed Inc. filed for a patent on insulin-laced toothpaste
which could replace the use of insulin shots for some diabetics.
 Flossing, which often causes some bleeding of the gums, could
help to speed the drug’s delivery to the bloodstream.
 Insulin Analogues
 Protein engineering has been used to produce variant forms of insulin,
known as insulin analogues with modified amino-acid sequences and
improved pharmacokinetic properties.

 Rapid acting analogues: Insulin lispro and insulin aspart are rapid-acting
analogues that have reduced self-association as a result of protein
engineering.

 Both are absorbed more rapidly than regular insulin and reduce post-
prandial glucose excursions more efficiently. Because of their short-lived
action, adjustments in basal insulin levels are required to achieve
improvements in overall glycemic control.
 Insulin complement
 One new drug Symylin is ready to be launched by Amylin Pharma, San
Diego.

 Symylin is a synthetic vergion of human hormone Amylin, which moderates

the glucose lowering effect of insulin. It is design to complement insulin
action and has been shown to reduce blood glucose without causing an
increase in hypoglycemic episodes.

 It could provide a potential adjunct to insulin therapy in both type I and type
II diabetes.
Vaccine Against Diabetes

 A world-leading medical trial conducted in Melbourne suggests

that the onset of type I diabetes could be prevented in many at-
risk people by a new nasal insulin vaccine.

 The phase II trial at The Royal Melbourne Hospital in children at

high risk of developing type I diabetes.