Oral-lynTM: Generex Biotechnology Corporation (Toronto, Canada) is developing a buccal insulin formulation based on RapidMistTM, an advanced buccal drug delivery technology. Oral-lynTM is a liquid formulation of human regular insulin with a spray propellant for prandial insulin therapy. The formulation results in an aerosol with relatively large micelles where the majority of the particles have a mean size >10 μm and therefore cannot go into the lungs. Each puff is claimed to deliver 10 U of insulin. The absorption rate of administered insulin as a puff is 10%, and that corresponds to 1 U when 1 puff of 10 U is delivered, which means 10 puffs will deliver 10 U insulin for a meal. Clinical studies in healthy volunteers and subjects with type 1 and type 2 diabetes have shown that the oral insulin spray was absorbed in direct relation to the amount given, and it had a rapid onset and a shorter duration compared with regular insulin given subcutaneously. In all of the studies conducted, the oral insulin spray was generally well tolerated. The only side effects included mild episodes of transient dizziness in some healthy volunteers and subjects with type 1 diabetes. The product is on the market in a number of countries (e.g., Ecuador and India). Without appropriately designed and performed phase 3 trials at hand, it is not possible to make any clear statement about the benefits/risk ratio of the different buccal insulins.
Oral insulin: Oral insulin has benefits in terms of compliance among patients, as well as physiological advantages because oral insulin can mimic the physiological fate of insulin through first pass to the liver, directly and effectively inhibiting hepatic glucose production. Since the initial discovery of insulin by Banting and Best in 1922, the oral form of insulin has been the elusive goal. Difficulties encountered for oral insulin delivery, since it is a protein, include degradation by the low pH of the stomach and the digestive enzymes in the stomach and small intestine. The major barrier for insulin absorption is the intestinal epithelium. All these factors lead to low bioavailability, and that leads to significant inter- and intra-subject
variability.
Nanotechnologies have brought some hope for improved delivery of insulin. Nanotechnology applications for delivery of hydrophilic drugs such as insulin might be achieved using biodegradable polymers such as chitosan, which has been extensively exploited for the preparation of nanoparticles for oral controlled delivery of several therapeutic agents. In recent years, chitosan cross-linked to various hydrophobic polymers has been utilized for the preparation of orally delivered drugs because of improved permeation and sustained release characteristics.
The newer products that are being tried include water-soluble, long-acting insulin derivative, [(2-sulfo)-9-fluorenylmethoxycarbonyl]3-insulin, vitamin B12-dextran nano particles, lipid nanoparticles, and PEGylated calcium phosphate nanoparticles as oral carriers for insulin. Protection of insulin from the gastric environment has been achieved by coating the nanoparticles with a pH-sensitive polymer that dissolves in the intestine at mild alkaline pH. In rats, oral insulin nanoformulation significantly (P<0.05) reduced blood glucose in normal and diabetic rats. Biocon (Bangalore, India) is manufacturing IN-105, which is in late phase 3. IN-105 is a human recombinant insulin conjugated with polyethylene glycol via an acetyl chain. It is orally bioavailable and stable at ambient conditions. Preclinical studies in different species have shown acceptable efficacy and safety. Its maximal circulating insulin levels after oral administration of 5 mg were observed after 20 minutes, and the maximum drop in glucose occurred at 40 minutes after oral administration. Phase 1 and phase 2 trials demonstrated that the absorption of IN-105 and the reduction in blood glucose levels were proportional to the dose administered.
Inhaled insulin: The inhaled products fall into two main groups: the dry powder formulations and solution, which are delivered through different inhaler systems. Exubera®, containing rapid-acting insulin in powder form, was studied in patients with type 1 and type 2 diabetes mellitus. The results of a patient preference study, using a comparison of utility scores, showed a greater preference for the inhaled route over insulin injection. However, issues like cost, the bulkiness of the device, and the small number of studies in subjects with underlying respiratory disease prevented widespread use of this new mode of delivery. Exubera® was available for less than one year, and then Pfizer took it off the market in 2007 because the drug failed to gain market acceptance.
Afrezza®: (MannKind Corporation, Valencia, CA, USA) is recombinant human insulin, using the Technosphere® concept and administered using a next-generation inhaler called Dreamboat ®. Technosphere® is a drug delivery system created by micro particles (2-3 μm) that form microspheres, which are then lyophilized into a dry powder for inhalation. Transdermal insulin: Transdermal insulin delivery is a needle-free alternative and avoids the disadvantages associated with other alternative routes such as the pulmonary and nasal routes. Permeation of compounds is limited to small, lipophilic molecules. The stratum corneum, the outermost layer of the skin, constitutes the major barrier for insulin permeation to reach useful levels. Several chemical and physical enhancement techniques such as iontophoresis, ultrasound/ sonophoresis, micro-needles, electroporation, laser ablation, and chemical enhancers have been explored to overcome the stratum corneum barrier to increase skin permeability.
Methods to improve transdermal delivery:
1. Chemical enhancers, which alter the lipid structure of the stratum.
2. Iontophoresis, which enhances the transdermal delivery of compounds via the use of a
small electric current.
3. Micro-needle technology, which involves the creation of micron-sized channels in the
skin, thereby disrupting the stratum corneum barrier and delivering the drug into the
epidermis without disruption of nerve endings.
4. Sonophoresis, which uses ultrasound and has been shown to increase skin permeability
of insulin. It is still being evaluated
insulin therapy
insulin therapy guidelines
insulin therapy simplification with insulin co-formulation
insulin therapy for type 2 diabetes
insulin therapy pdf
insulin therapy indication
insulin therapy ppt 2019
insulin therapy in hospital
insulin therapy ncbi
insulin therapy and hypoglycemia
insulin therapy algorithm
insulin therapy a valuable legacy and its future perspective
insulin therapy and hypokalemia
insulin therapy ada
insulin therapy ada guidelines
insulin therapy american diabetes association
insulin therapy and type 2 diabetes
insulin therapy benefits
insulin therapy book pdf
insulin therapy before surgery
insulin therapy brings about which electrolyte change
insulin therapy book
insulin therapy bnf
insulin therapy blood glucose levels
insulin therapy brain injury
insulin therapy contraindications
insulin therapy complications
insulin therapy coma
insulin therapy classification
insulin therapy compliance
insulin therapy can be administered by an oral medication or by injection
insulin therapy chart
insulin therapy calculation
insulin therapy diabetes
insulin therapy diabetes type 1
insulin therapy definition
insulin therapy dose
insulin therapy during pregnancy
insulin therapy diabetes type 2
diabetes melitus tipe 2 insulin therapy
insulin therapy diabetes mellitus
insulin therapy education
insulin therapy explanation
insulin therapy effects
insulin therapy example
insulin therapy edema
insulin therapy evolution
insulin therapy errors
insulin therapy emedicine
insulin therapy for hyperkalemia
insulin therapy for diabetes
insulin therapy for type 1 diabetes
insulin therapy for gestational diabetes
insulin therapy for type 1 diabetes pdf
insulin therapy for diabetes mellitus
insulin therapy for schizophrenia
insulin therapy guidelines 2021
insulin therapy guidelines pdf malaysia
insulin therapy guidelines 2020
insulin therapy gestational diabetes
insulin therapy gdm
insulin therapy guidelines ada
insulin therapy geriatrics
insulin therapy hypoglycemia
insulin therapy hypokalemia
insulin therapy health education
insulin therapy history
insulin therapy hospitalized patients
insulin therapy has all of the following effects except
insulin therapy hypocalcemia
insulin therapy hindi meaning
insulin therapy in diabetes
insulin therapy in critically ill patients
insulin therapy in hospitalized patients
insulin therapy in diabetes ppt
insulin therapy in gestational diabetes
insulin therapy in type 2 diabetes
insulin therapy journal
insulin therapy journal article
insulin therapy in juvenile diabetes
insulin therapy kya hota hai
insulin therapy knowledge
insulin therapy kya hai
insulin therapy in chronic kidney disease
insulin therapy for diabetic ketoacidosis results in
insulin therapy and kidney disease
insulin therapy for diabetic ketoacidosis in dogs
practical guide to insulin therapy kkm
insulin therapy leaflet
insulin therapy leahy
insulin therapy literature
insulin therapy levels
insulin lipodystrophy therapy
insulin as first-line therapy
insulin as first line therapy in type 2 diabetes
insulin lowering therapy
insulin therapy mental health
insulin therapy meaning
insulin therapy made easy
insulin therapy mechanism of action
insulin therapy made easy pdf
insulin therapy medscape
insulin therapy malaysia
insulin therapy malayalam
insulin therapy nursing management
insulin therapy nhs
insulin therapy nice guidelines
insulin therapy nursing care plan
insulin therapy not working
insulin therapy notes
insulin therapy nondiabetic
insulin therapy of diabetes mellitus
insulin therapy of diabetes type 2
insulin therapy of gestational diabetes mellitus
insulin therapy onset and duration
insulin therapy of hyperkalemia
insulin therapy osce
insulin therapy overdose
insulin therapy other name
insulin therapy pdf free download
insulin therapy ppt for nurses
insulin therapy ppt 2020
insulin therapy ppt free download
insulin therapy ppt
insulin therapy protocol
insulin therapy qualitative study
insulin therapy regimen
insulin therapy review
insulin therapy review article
insulin therapy resistance
insulin therapy racgp
insulin therapy results
insulin therapy reaction
insulin therapy ratio
insulin therapy schizophrenia
insulin therapy side effects
insulin therapy sliding scale
insulin therapy strategies
insulin therapy side effect
insulin therapy surgery
insulin therapy shot
insulin therapy types
insulin therapy type 1 diabetes
insulin therapy type 2 diabetes
insulin therapy t2dm
insulin therapy target
insulin therapy type 2 diabetes guidelines
insulin therapy type 2
insulin therapy the discovery that shaped a century
insulin therapy uses
insulin therapy uptodate
insulin therapy unit
insulin therapy update
insulin potentiation therapy uk
insulin pump therapy uk
insulin therapy patient uk
diabetes insulin therapy uk
insulin therapy validity
early insulin therapy in very-low-birth-weight infants
insulin pump therapy vs mdi
intensive insulin therapy versus conventional
insulin pump therapy vs multiple daily injections
insulin shock therapy video
intensive insulin therapy versus conventional glucose control
voluntis insulin therapy manager
insulin therapy wikipedia
insulin therapy with insulin aspart (novolog®) that mimics the bodys basal insulin secretion
insulin therapy weight gain
insulin therapy when
insulin therapy with diabetes mellitus
insulin therapy with chemotherapy
insulin therapy withdrawal
insulin therapy when to take
insulin therapy youtube
insulin therapy in young adults
insulin therapy development beyond 100 years
insulin potentiation therapy new york
insulin therapy guidelines pdf
insulin therapy guidelines malaysia
insulin therapy guidelines 2019
insulin therapy guidelines 2018
insulin basal
insulin basal bolus
eadsg guidelines insulin therapy in diabetes
easd guidelines insulin therapy in diabetes
diabetes insulin therapy guidelines
guidelines for insulin therapy
guidelines for insulin therapy in type 2 diabetes
insulin therapy guidelines in pregnancy
intensive insulin therapy guidelines
initiating insulin therapy guidelines
insulin therapy guidelines 2017 malaysia
insulin pump therapy nice guidelines
insulin therapy in type 2 diabetes nice guidelines
guidelines of insulin therapy
insulin pump therapy guidelines
insulin therapy a pocket guide
starting insulin therapy guidelines
insulin intravena
insulin therapy for type 2 diabetes ppt
insulin therapy for type 2 diabetes guidelines
insulin therapy for type 2 diabetes mellitus pdf
insulin therapy for type 2 diabetes pdf
insulin regimen for type 2 diabetes
insulin pump therapy for type 2 diabetes
side effects of insulin therapy for type 2 diabetes
ada guidelines for insulin therapy in type 2 diabetes
conventional insulin therapy type 2 diabetes
insulin untuk dm tipe 2
insulin untuk dm tipe 1
insulin untuk diabetes tipe 2
insulin untuk diabetes melitus
terapi insulin untuk dm tipe 2
insulin untuk diabetes
what is insulin therapy for type 2 diabetes
insulin therapy in type 2 diabetes ppt
insulin regimen in type 2 diabetes
insulin treat type 2 diabetes icd 10
initial insulin therapy for type 2 diabetes
insulin therapy in type 2 diabetes mellitus pdf
insulin therapy for type 2 diabetes mellitus
insulin therapy in type 2 diabetes mellitus uptodate
insulin treat type 2 diabetes mellitus
insulin treat type 2 diabetes mellitus icd 10
insulin therapy in patients type 2 diabetes mellitus
the role of insulin pump therapy for type 2 diabetes mellitus
non-insulin therapies for type 2 diabetes
types of insulin therapy for type 2 diabetes
oral insulin therapy type 2 diabetes
resource utilization with insulin pump therapy for type 2 diabetes mellitus
insulin replacement therapy type 2 diabetes
support for insulin therapy in type 2 diabetes
typical insulin regimen for type 2 diabetes
insulin suntik diabetes
icd 10 code for type 2 diabetes mellitus with insulin therapy
insulin pump therapy pdf
insulin therapy in diabetes pdf
sliding scale insulin therapy pdf
basal bolus insulin therapy pdf
terapi insulin adalah pdf
complications of insulin therapy pdf
insulin pdf
terapi insulin pdf
insulin kerja pendek
indikasi terapi insulin
types of insulin therapy pdf
terapi insulin perkeni pdf
practical guide to insulin therapy pdf
insulin basal contoh
insulin therapy indications
intensive insulin therapy indication
insulin glargine therapeutic indication
insulin aspart therapeutic indication
insulin lispro therapeutic indication
insulin basal adalah
insulin short acting contoh
insulin short acting
indication for insulin therapy
indication of insulin therapy in type 2 diabetes
insulin iv
indication of insulin therapy
insulin ppt
insulin therapy in hospitalized
insulin therapy for the management of hyperglycemia in hospitalized patients
intensive insulin therapy in hospitalized patients a systematic review
insulin pump therapy in the hospital setting
insulin therapy and pen use in hospitalized patients
insulin pump therapy in the hospital
insulin therapy in type 2 diabetes pdf
insulin dose in type 2 diabetes
insulin dosing in type 2 diabetes
insulin dosage in type 2 diabetes
early insulin therapy in type 2 diabetes
starting insulin dose in type 2 diabetes
icd 10 insulin treat type 2 diabetes mellitus
icd 10 code for insulin treat type 2 diabetes mellitus
insulin treats type 2 diabetes mellitus quizlet
insulin treat type two diabetes mellitus
patients with insulin-treat type 2 diabetes mellitus
insulin treatment of type 2 diabetes mellitus
targeting insulin-degrading enzyme to treat type 2 diabetes mellitus
non-insulin prescription treatments for type 2 diabetes
insulin therapy for type ii diabetes in not effective because this condition is characterized by
harga suntik insulin diabetes
efek suntik insulin diabetes
biaya suntik insulin diabetes
cara suntik insulin diabetes
suntik insulin obat diabetes
icd 10 code for uncontrolled type 2 diabetes mellitus with insulin therapy
basal-bolus insulin regimen pdf
insulin pdf 2020
insulin pdf slideshare
insulin pdf 2019
pdf insulin resistance
pdf insulin sliding scale
pdf insulin hormon
jenis insulin pdf
sop terapi insulin pdf
indikasi terapi insulin pdf
contoh insulin kerja pendek
insulin basal contohnya
contoh insulin basal dan prandial
insulin glargine clinical indications
insulin lispro clinical indications
insulin basal adalah pdf
insulin basal bolus adalah
contoh insulin basal adalah
insulin basal dan prandial adalah
insulin short acting and long acting
insulin short acting intermediate long acting
insulin short acting brands
insulin short acting pen
insulin lispro short acting
regular insulin short acting
actrapid insulin short acting
indications for insulin therapy
insulin treatment in type 2 diabetes
indications for insulin therapy in type 2 diabetes
benefits of insulin therapy in type 2 diabetes
insulin iv bolus
insulin iv vs subcutaneous
insulin iv dose
insulin iv drip
insulin iv vs sc
insulin iv to subcutaneous
insulin iv push for hyperglycemia
insulin iv injection
indications of insulin therapy
contraindication of insulin therapy
insulin ppt pharmacology
insulin ppt download
insulin ppt for nurses
insulin ppt 2019
insulin ppt 2018
insulin ppt in hindi
insulin ppt background
insulin ppt indonesia
guidelines for the safe management of insulin pump therapy in hospital
