Formulation and characterization of liposomal spray dried powders intended for inhalation

Abstract

This master thesis has evaluated the possible use of a spray dryer to produce powders suitable for use as inhalants and whether the addition of liposomes to the solution to be spray dried would improve the properties of the powder. The powders created consisted of Lysozyme as model drug, Lactose as filler and stabilizer, and different types of phospholipids to create liposomes using an ethanol injection method.
It was shown that powders suitable for use as inhalants were possible to create. By adjusting the parameters of both the spray dryer and by changing the proportions of the ingredients it was possible to achieve various powders, some of which displayed strong signs of having the proper parameters for use for inhalation.
The quality parameter deemed most important for the powders was the fine particle fraction, which corresponds to the fraction of powder that reaches the target area of the lungs. The fine particle fraction was tested using a cascade impactor and it was discovered that this fraction was dependent on the concentration of both lysozyme and liposomes as well as the inlet temperature and feed flow rate of the spray dryer.
The detected fine particle fraction varied between just a few percent for some of the powders without liposomes up to more than 50 % for one of the powders created using liposomes.
Other investigated parameters were the water activity (important for the stability of the powder), the liposome size distribution (to see how this affected the particles), the yield and the outlet temperature from the spray dryer.

Popular Abstract

Creating a fat powder for inhalation
By using tiny fat bubbles, is it possible to improve a protein powder intended for inhalation? This question was the basis of this thesis, and the answer seems to be in the positive.
So how do you get a protein medicine, such as insulin or a vaccine, into the body? The usual answer is to inject it, as it doesn’t survive the stomach, but a recent trend is to try to breath it in instead. This would be an improvement for many reasons, as first of all no one likes needles, let alone having to use one on yourself several times a day. But for it to be breathed in, there are several problems. How does one make the protein become absorbed by the lungs and enter the blood? One answer is to make sure the medicine is in particles small enough to be breathed in to the very bottom of the lungs, where it can easily pass through the thin boundary between the air and the blood. These small particles are often called fine particles, and obviously it is better for more of the medicine to consist of these fine particles, but in reality many medicines only have half of the medicine in this size range.
To create such small particles special equipment is needed. One such device is the spray dryer, which is a device for turning a liquid into a fine powder. By tweaking the settings, it is possible to create a powder with particles small enough to reach the bottom of the lungs.
The powder we produced consisted of lysozyme, a protein, lactose, used mainly as something to take up space and make the powder cheaper, and different types of fat in the form of liposomes. The powers were created both with and without these liposomes to test what effect their presence had. It was tested for not only its size, but also for its water activity and the yield of the spray dryer that created the powder. Water activity is a term for the humidity of the powder, which is important as it affects how long the powder can be stored before it is destroyed.
An effect of most protein medicines is that when the protein has reached the blood, it quickly has its effect and is then quickly removed. This is sometimes great when you need a quick effect, but sometimes you want something with a lasting effect instead. For these occasions, one tactic is to have the protein kept inside of a tiny fat bubbles called a liposome. By having the protein inside of the liposome it takes a longer time for it to be released into the blood and in consequence makes it last longer. This effect was not studied in this project, but instead it was studied if the liposome had any other effect on the powder.
It was discovered that when you added liposomes to the powder, a lot of things happened. The powder became stickier and the yield became lower. On the other hand, the amount of fine particles became larger; in fact, it more than tripled for one of the powders with liposomes when compared with a powder created the same way but without the liposomes. All powders created with liposomes had more fine particles than any created without them, leading to the conclusion that the addition of liposomes were indeed a step forward.
This discovery, that there is not only a potential increase in effective time of the medicine in the body, but also a significant effect on the amount of fine particles in the powder could be used to improve the powders created for inhalation purposes after further studies.

• author: Kullenberg, Fredrik
• supervisor: Ingegerd Sjöholm; Mårten Svensson; Ian Harwigsson
• organization: Food Technology and Nutrition (M.Sc.)
• course: KLG920 20161
• year: 2016
• type: H2 - Master's Degree (Two Years)
• subject: Medicine and Health Sciences; Technology and Engineering
• keywords: Impactor, Phospholipid, Liposome, Spray Drying, Inhalation, Fine Particle Fraction, Pharmaceutical Technology, läkemedelsteknologi
• language: English
• id: 8875260
• date added to LUP: 2016-06-10 10:17:09
• date last changed: 2016-06-10 10:17:09