Will buccal insulin succeed in the market…..?

Oral Recosulin is a rapid mist technology which allows precise insulin dose delivered via simple, cosmetically acceptable metered dose inhaler in form of fine aerosolized droplets directly into the mouth. This technology utilizes the formation of micro fine thin membranes to encapsulate and protect the insulin molecule. The system introduces fine particulate aerosol at high velocity (100 miles per hour) into the patient’s breath. The mouth deposition is dramatically increased compared with conventional technology. This oral aerosol formulation is rapidly absorbed through the bucal mucosal lining and in the oropharynx region. It provides the plasma insulin levels necessary to control postprandial glucose rise in diabetic patients.

This novel, pain free, oral insulin formulation has a critical series of attributes:
1. Rapid absorption
2. Simple (user-friendly) administration technique
3. Precise dosing control
4. Bolus delivery of drug

Dosage and administration:
One puff of oral-recosulin delivers 10 units of regular insulin. Approximately 1 unit of regular insulin is absorbed into systemic circulation of patient after taking 1 puff of oral-recosulin.
The patient should be relaxed and breathing normally. The mouth piece of the device placed in mouth at the end of normal exhalation. The patient sprays oral-recosulin into the mouth. Patient is asked to hold breath for 5 second (by counting slowly to 5)
This procedure is repeated until correct numbers of puffs are administered.
It is recommended that oral-recosulin be given in divided doses with 50% of the dose before the meal and remaining after the meal.

The indications of oral-recosulin are:
1. Oral-recosulin is indicated depending on the type of diabetes.
2. It is recommended as bolus insulin for use with basal insulin for better compliance and control of postprandial glucose rise.
3. It can be used in combination with sulfonylureas, metformin and pioglitazone and other anti-diabetic agents for glycemic control in patients who do not achieve satisfactory glycemic control with oral therapy alone.
4. It can be used for insulin initiation in patients needing insulin for diabetes control.
5. It can be used for control of postprandial hyperglycemia in igt patients not adequately managed with standard treatment protocol.
6. It can be used for achieving glycemic control in ifg patients not adequately managed with standard treatment protocol.

Unique features:
It has been shown to be fast, flexible, safe and simple. Most important it is well accepted by both patients as well as doctors
1. Needle free, pain free therapy: intensive diabetes therapy requires at least 3-4 injections per day. Oral-recosulin provides needle free administration of insulin for treatment of diabetes
2. Rapid insulin absorption: oral-recosulin is absorbed in blood stream faster than injected insulin
3. Short duration of action: acts similar to rapid acting insulin analogue for control of postprandial glucose rise.
4. No risk of hypoglycemia: rapid absorption avoids prolonged tail exceeding postprandial state as common with subcutaneous insulin.
5. Higher patient compliance: needle free, pain free insulin therapy should increase compliance
6. Better quality of life: the small size of device makes it convenient to carry anywhere and to use comfortably in public. Since dosing time before meal is greatly reduced this offers a more flexible lifestyle. The improved compliance, which leads to a better quality of life.

The Debate
--> Though the main advantage of Oral Buccal insulin is to avoid injection prick, a long acting/intermediate insulin has to be injected anyway. So injection cannot be completely avoided.
--> Moreover when only 1 unit of insulin is systemically absorbed with 1 puff, it will be cumbersome for a patient requiring >10 units of insulin. So its difficult for patients who need >20 units of insulin
--> The droplets may not be deposited in the lung parenchyma but there is no literature to explain their deposition elsewhere in the respiratory tract during accidental inhalation.
--> As insulin treatment has to be continued for years together, the long term effect particularly carcinogenic effect on the buccal mucosa is unknown.
--> It’s bioavailability while taking hot or cold food is not known
--> The cost of a single puff is more than rs.1000. A patient may need at least 20-25 puffs/day minimum. So the daily expenditure for insulin is very high
--> In a country like USA where insurance covers a patient’s expenditure on hospitalization & medicine, exubera (nasal insulin) was not affordable. Similarly buccal insulin which carries same disadvantages like exubera may have to struggle in the market to establish its place
--> Probably the time will give us the result.

Onset of action - 10 minutes
Peak level - 50 minutes
Duration of action - 150 minutes
Bioeffectiveness - 7-10% of s.c. injected insulin when given in same dose