In diabetology, oral insulin spray is a fascinating area for research and development. Numerous lives have been saved by insulin since its discovery in 1922. However, many doctors (and their patients!) requested non-injectable insulin delivery methods due to the challenges of subcutaneous administration, frequent self-monitoring of glucose, and the non-physiological action profiles of insulin.

Joslin tried the first oral insulin preparations in 1922 and 1923, but the results were not good. Numerous researchers have explored this idea since then but to no avail. However, a few insulin molecules intended for oral administration are undergoing clinical trials and should soon be used in clinical settings. 

This article examines the current state of oral insulin. It does not address approaches for which work has ceased; instead, it concentrates only on those preparations that are currently under development. The paucity of clinical data on this subject accounts for the review’s brief length. 

Current methods of Insulin delivery and their limitations  

1. Syringe 

Insulin is administered by needle with syringes and insulin pens. In comparison to syringes, pens might be more practical and more comfortable for kids.

The doctor will determine the amount of insulin required for each dose. Syringes with smaller capacities are more accurate and more straightforward to use. If the dosage changes, purchase the next size if the most significant dose is almost at the syringe’s maximum capacity. Select a syringe with half-unit markings if you require doses in those increments.

The drawbacks are that they are heavy and that mastering the ideal syringe technique takes time and practice. Moreover, there may be disadvantages to the necessary syringe manipulations in social settings, such as the workplace, classroom, and public areas like department stores, playgrounds, and restaurants.

2. Insulin Pen

Certain pens require inserted cartridges to function. Once the insulin has been used, the others are pre-filled and thrown away. Insulin is injected using a needle after calibrating the dose on the pen.

The gadgets may improve glycemic control and provide greater flexibility to lifestyle choices.37–38. Although insulin dosage accuracy varies amongst pens, it is still superior to results from conventional syringe studies.

3. Insulin Pump 

The size of an insulin pump is comparable to a tiny cell phone. It provides an hourly basal dose of either short- or rapid-acting insulin. You determine the dosage when you eat or when your blood sugar is elevated, and the insulin in the pump administers the bolus.

A thin plastic tube semi-permanently inserted into the fatty layer beneath your skin—typically in the stomach region or the back of the upper arm—delivers insulin via the pump. You will be shown by your physician or a health education specialist where to put the tube.

When compared to the use of conventional syringes and vials, insulin pump therapy is significantly more expensive. In a clinical trial, patients who were at risk of hypoglycemia regularly were the only ones for whom the cost/benefit ratio was considered favourable.

4. Insulin Inhaler 

To provide ultra-rapid-acting insulin at the start of meals, inhaled insulin is administered orally using an inhaler. Long-acting injectable insulin is used in conjunction with inhaled insulin.

Discuss your needs or lifestyle change with your diabetes educator and doctor. They will be knowledgeable about the newest gadgets and offer advice on managing diabetes in all its forms, including insulin administration. 

How does the new oral insulin spray work? 

Insulin injections are necessary for diabetics, particularly those with type 1 diabetes, to control their blood sugar levels daily. However, giving insulin injections can be uncomfortable and painful, mainly outside the home or office.

The announcement by the Hyderabad-based company NiedlFree of an insulin oral spray, Ozulin, a needle-free substitute, can potentially revolutionize diabetes treatment if approved. The fact that the dosages can be sprayed straight into the mouth makes it a practical choice.

The oral insulin spray’s tasteless liquid aerosol mist formulation is applied to the buccal mucosa through a patented delivery system. However, the formulation functions more like synthetic fast-acting insulin analogues; the active pharmaceutical ingredient is recombinant human insulin.

Researchers have demonstrated that, compared to regular insulin administered subcutaneously, the oral insulin spray had a quicker onset and shorter duration of action and was directly absorbed in proportion to the amount administered in clinical studies involving healthy participants and those with T1DM and T2DM.

Research published in the Nature journal Scientific Reports suggests that spray drying can produce dry insulin nanoparticles, which could lead to the development of bioadhesive films or oral tablets as dosage forms.

Oral Insulin Spray – Clinical trial Results 

Large-scale clinical trials have demonstrated that in both type 1 (T1DM) and type 2 (T2DM) diabetes, achieving better glycaemic control significantly lowers the risk of microvascular complications over the long term. A novel insulin spray formulation and delivery system is an alternative to injectable and inhaled insulin. The apparatus facilitates the aerosolized spray delivery of a liquid oral insulin formulation into the oral cavity. 

The oral insulin spray was generally well tolerated in every study. During the dosing process, a small amount of mild dizziness occurred in a few healthy and T1DM subjects; these symptoms were mild and self-limited. No modifications were observed in the vital signs, laboratory values, or physical examination outcomes. 

Numerous biological barriers, whether anatomical or physiological, have long been viewed by pharmaceutical researchers as hindering the development of an effective non-penetrative insulin drug delivery system. The amount of insulin that can enter is restricted by these barriers.