TURBUHALERS

Introduction
The inhalation of medication through Dry powder inhalers (DPI) is becoming increasingly more popular amongst the pharmaceutical market. This is because this technique of drug administration is very effective in delivering the drug to the patient and the actual method of administration itself has a low incidence of side-effects. Furthermore, medication that directly enters the patients respiratory system in this technique pose fewer adverse effects compared to oral medication. The drug is also able to take its effect for the treatment of the condition that the inhaler is used for in a very short period of time which again is another advantage in comparison to oral medication (Kumaresan 2006). The Turbuhaler fits into the categories of the Dry powder inhaler which is specifically designed to accomplish this sort of drug administration. Its design and mechanism of use is more preferred by many users over the conventional aerosol metered-dose inhalers because patients find that Turbuhalers are easier to use. They do not contain potentially harmful carbon propellants, lubricants and surfactants which aspire to have ill consequences on the health of the patient unlike other inhalers (Bisgaard 2001). Turbuhalers are newly developed breath actuated devices which function by preloading them with around 200 doses of medication such as salbutamol (500 ). Each one of the doses is dispensed by rotating a plastic ring at the base of the inhaler, with the absence of carrier powders or propellants, allowing the drug to be inhaled in its purest form. However, many patients cannot encompass the full benefit of using a Turbuhalers even when first made to have careful tuition because of the poor techniques implemented during the procedure. The inability to correctly use this inhaler is most frequently encountered by patients who improperly synchronize inhaler actuation with inspiration. The efficiency of this device is directly dependent upon the generation of adequate inspiratory flow when breathing in. Many users, especially asthmatic users or users that have other severe respiratory illnesses can not produce a high enough force when inhaling to obtain the recommended inspiratory flow and find this difficult to achieve through no fault of their own due to their illness. There are several disadvantages that have been associated with the use of DPIs which require improvements to be made on the design of the device to further progress its function (Smith 2002). A typical Turbuhaler DPI contains medicine conditioned to be in powder form which is inhaled using this device so that it can enter the respiratory system. The inhalation is preceded either through the mouth or the nose. In this device, the powder comes from a prefilled container that is punctured before inhaling. The inhalation requires to be deep and fast to ensure a correct quantity of the administered drug comes out of the inhaler and enters deep within the lungs. There are many different types of Turbuhalers available in the market but they all use the same theory and mechanism in delivering the drug (The Ohio State University 2009).

Design and operation

The Turbuhaler fits into the category of a dry powder inhaler and is compacted with a high enough dosage of medication so that it can be used up to 300 times per instillation of the drug. The mechanism entailed that allows the delivery of the drug by this device to the patient is in the form of breath-actuated inhalation. Its design is compromised of 13 components and a metal spring. The medication contained within the Turbuhaler is in the form of a pure, fine, additive free, dry powder such as budesonide and turbutaline which are drugs commonly administered by patience through the use of this device. If the device is activated a second time either inadvertently or deliberately the patient would find that it would not be possible to inhale a double dose, as only a single dose capable of being aligned by the device at any time with the inhalation channel as shown by figure 1 (Daniella.B
2012).

The Turbuhaler relies upon the force of inspiration to elevate particles which are deposited on a dosing disc within the container of the device, which travels by these applied forces caused by suction into the patients respiratory system. When inhalation is preceded through suction on the mouthpiece of the Turbuhaler, the fine powder particles are forced to travel through the inhalation channel towards a disaggregation zone where the powder particles are disintegrated and separated. This part of the Turbuhaler consists of two spiral channels designed to create turbulent air flow hence the name Turbuhaler. This newly created flow of air breaks the powder particles into even smaller units thus creating a more therapeutically effective drug. This is because the size of the powder by this stage of the process are roughly less than 7 in diameter thus allowing the drug absorption by the respiratory system to be done at a faster rate (Daniella.B 2012). Studies that have been conducted show that the minimum required inspiratory flow rate to attain a therapeutic dosage is at least 30 L/min. This makes the effectiveness of the medication greater promoting the treatment of the condition. This is a low target flow rate in comparison to other inhalers that use a similar mechanism, therefore making this device increasingly more desirable in treating acute and severe asthmatic patience in the emergency department. However, a further increased inspiratory flow has increasing benefits as there would be a higher lung deposition of medication as both relationships are directly proportional. For this reason, it is important to teach and encourage patience to inhale forcefully when using this device (Daniella.B 2012).

Figure 1: Image showing the design and internal layout of a Turbuhaler (Nesbitt 2006)

Step by step instructions on how to use a Turbuhaler

Table 1: Step-by-step instructions on how to use a Turbuhaler (Nesbitt 2006)
Steps required to follow (Suggested demonstration and detailed guidance) 1) Remove outer plastic cover Explanation to reference procedures with Included photos for clearer justification Cover used to keep inhaler clean and free from contamination. Also provides protection against humidity and other liquids

2) When placing the powdered medication into the inhaler ensure that the Turbuhaler is in an upright position so that the mouthpiece is directed upwards.

3) When loading the device what requires to be done is to rotate the coloured handle in one direction as far as possible; then it is required to rotate it back into the opposite direction until a click noise is heard. This is an indication by the device that it has prepared a correct dose. It is not possible to load the device more than one dose at a time without having to undergo this procedure once medicine has been inhaled as the measuring device is not compactable to hold more than one does at a time

The Turbuhaler must be held upright at a angle between 45o-90o otherwise the measuring device will not fill correctly and you either over load or under load the device with the powder. This will mean a proper dose will not be administered if under loaded or the medication may go to waste if over loaded What has been noticed when patience carry out this step is that they shake the inhaler as they have adapted this habit when associating with the use of PMSIs. This step is not required as there is nothing to mix and could in fact have a negative consequence as it could potentially cause some of the loaded dose to be lost.

4) It is important to ensure that when inhaling it is done forcefully and deeply by placing mouth piece between the teeth and closing lips around it, so that all the air entering goes first through the inhaler. Many times patients are not able to feel or even taste any of the medication as it is being supplied at a very low dosage and is in very fine powder form.

Another noticeable mistake made by many patience is that they at times actuate the device twice or even three times before loading. Any dosages loaded after the second time would be returned to the reservoir which means that it would go to waste. This occurs because the dosing indicator wheel will still advance each time the handle is rotated. It is important that the patient is aware of the openings found on the side of the Turbuhaler. When using the device, air must enter here first before medication can be inhaled and is also important for turbulent conditions to be created. Many of the devices are designed to signal a successful administration. This occurs as some Turbuhalers are designed to have auditory indicators whilst others have light indicators. By using these types of Turbuhalers the patient would become increasingly more motivated to exercise correct techniques as Patients may be unable to smell, taste or even feel the sensation

of the fine ( Continuous....) Particles as there is such a small quantity of medication given in each dose. These indicators would reassure patients that they have received their medication in a correct manner and quantity.

5) When exhaling once device has been used it must be ensured that the exhaled air does not enter the inhaler. This is because the powder inside could be blown away and also humidity cannot be introduced to the inhalers

Humidity introduced into the inhaler would cause aggregation of the powder particles forming clumps and ultimately block the air from travelling through the inhaler. This humidity is commonly caused by exhaling air into the inhaler which has devastating consequences to the device. This may cause small holes in the dosing disk to form and could also cause other parts of the device to become partially or fully blocked due to the contact between liquid caused by the humid air and powder particles. This would result in doses being administered at unspecified quantities or even make the drug unobtainable.

6) Once medication has been inhaled the patient can breathe normally without the need to worry if drug is being absorbed by the body. Again exhaling needs to be done away from the inhaler.

7) In case the first dose does not seem effective enough in relieving the illness, or if a qualified professional prescribed a higher dosage, the steps 1-6 need to be repeated to have a successful second administration. 8) The protective cap requires to be screwed back on 9) Clean the outside of the mouthpiece once a week

Recent studies have shown that it is not necessary to hold the breath or change breathing patterns after inhalation of the medication. As the powder dissolves as soon as there is contact made with the membrane which happens instantly on the first breath of inhalation. Many patients require a higher concentration of the medicine as that prescribed by the device in one dosage. These instructions must be completed in a correct manner to ensure that the medication is delivered in the most effective approach possible. It is important when carrying out this stage that the patient does not accidently reload the device by turning the bottom plastic handle. It is important to ensure that no liquid is used to carry out this procedure

Lung delivery of medication using a dry powder inhaler (Turbuhaler)

A Turbuhaler can be used to treat conditions such as Asthma and Severe chronic obstructed lung disease. Acute asthma is a condition which is associated with considerable inspiratory and expiratory airflow limitations. One drug that could be extracted and stored by loading it in a Turbuhaler and thus inhaled by the mechanism it entails is salbutamol which is a very effective drug in treating the mentioned conditions. A traditional device that was employed to be used as an inhaler for this medication was a chlorofluorocarbon containing inhaler device such as the aerosol metered-dose inhaler. However, these inhalers containing this chemical have shown to pose great danger to the consumers health and therefore are being banned on an international scale. Instead, Turbuhalers are replacing these devices as they are much more effective and contribute to no serious side effects which is another reason to why they are becoming increasingly more popular. Another point worth noting is that a Turbuhaler overcomes a lot of the poor inhaler techniques used by other inhalers, as its much easier to use and requires reasonably less effort to inhale which is especially important for people who have respiratory illnesses such as asthma (Prat 2008). However, people with severe conditions may not be able to generate an adequate inspiratory flow and therefore extract enough medication to prevent or provide relieve for their illness. Not enough research has been conducted regarding this topic, like for people who have acute asthma; it is not yet clear if they are able to generate adequate flow especially when the condition is taking its effect in the severest form. To make things more clear regarding this issue research was conducted in which 99 hospital patients were investigated who had acute exacerbation of asthma. Several variables were measured during the investigation such as Peak inspiratory flow through an empty Turbuhaler, while the same was measured again without this device present. To make this investigation more unambiguous and more reliable the patients that took part were studied prior to nebulised bronchodilator therapy. Several parameters were determined by conducting this investigation which included the average forced expiratory volume of the 99 patients in one second and was measured to be 1.2L while the mean forced vital capacity, which is the maximum amount air that can be inhaled or exhaled by the lungs at one time, again measured over a period of 1 second was 2.1L. The peak expiratory flow was measured as being on average 199L/min whereas the peak inspiratory flow was measured to be 152L/min, both measurements were taken in the absence of the Turbuhaler (Brown 1995). It is not unusual that the forced exhaled air has been measured to be greater than the forced inhaled air. This is because the lungs always have a certain amount of air present even when the patients believe that they have fully exhaled. Forcing this air out does decrease the amount of air already present but does not eliminate it fully. So when forcefully exhaling air, not only does the air that was inhaled exit but additionally, also some of the reserved air that is always present in the lungs. Also once breathing is continued as normal, the quantity of air that is always present returns back to its normal quantity which remains constant as long as

breathing is carried out in a normal manner. Due to the presence of this air that always exists in the lungs, when inhaling not as much air can enter the lungs (ehow 2008). The mean peak inspiratory air when inhaling through a Turbuhaler was measured to be 60L/min while the Peak expiratory air subsequent to breathing through a Turbuhaler was found to be 89L/min. After carrying out this investigation and analysing the data collected it was found that two patients failed to produce the minimum inspiratory flow that is required for a successful administration of medicine through the employment of a Turbuhaler which is 30L/min. Both these patients recorded an intake of air through a Turbuhaler of 26L/min which if practiced in an actual situation where the drug was loaded into the device would not be sufficient enough to intake a correct quantity of the medication. From the research carried out 98% of patients with acute asthma generated a high enough inspiratory flow when inhaling through a Turbuhaler which would therapeutically activate a correct amount of bronchodilator medication such as salbutamol to be delivered to the airways relieving the sufferer of the condition. Nevertheless, due to the severity of the conditions a Turbuhaler is generally used to treat, it is very important that especially in times of emergencies a Turbuhaler can be used safely and effectively by all patients. As not everyone was able to seek the full benefits of this device, and even though it is only a very small percentage of people, there could still be improvements made to the inhaler design such as installing a assisted air flow component to the device for the weaker population to further reduce the minimum amount of inspiratory air flow required (Brown 1995).

Advantages of using Turbuhalers

By this stage the reader should be aware of the many benefits when using this type of inhaler. A summary of all the benifits will be given in this section of the report which have already been mentioned together with additional benefits that have not yet been considered. Below is a list of all the benefits patients have found when using this device (UHN 2011): Patients have generally found that a Turbuhaler is easy to use The inhaler is of convenient size so making it portable Little or no taste of medication due to the very small amount of dose the inhaler dispenses in each loading. Also there is very little or no sensation of the drug when inhaling it making it a more comfortable experience when administrating Inhaled medication itself has many benefits as its much more fast acting and has a considerably reduced amount of side effects Compatible for a wide variety of medication Can store a large enough quantity of medication so has multiple dose capacity of up to 200-250 inhalations at a time so there is no need to constantly re-fill the inhaler device with medication Grip attachment for patients who have arthritic or restricted finger movement when turning device to load dose

Low inspiratory flow rate required of 30-60L/min which is easily achieved even by weaker patients that have severe conditions thus allowing most patients to use it Installation of whistle or light on device to give indication of a successful and adequate inspiratory flow Can generally be used for a wide variety of people even if the severity of the condition required to be treated is high Only requires one forceful inhalation by breath-actuation so requires no breath coordination unlike other inhalers such as metered-dose inhalers making them more efficient to use CFC free so imposes no serious risks to the user and therefore has a very minimum amount of adverse side effects Allows medication to directly target the lungs therefore medication has a rapid onset. This method of administration has lower side effects. As nothing in the actual device is being used up it therefore can be re-used even when first batch of medication has been used by just simply replacing the medication that has been administered Inhaler is set to extract a set quantity of medication in each dose making the extraction procedure easier as the patient does not need to worry about the quantity of medication needed to extract thus making it also easier to keep a record of quantity of drug taken Relatively cheap to purchase

Problems Associated with the use of Turbuhalers

As with any device there are some disadvantages and even flaws found in the actual design and operation process which have been established by patients who are using this inhaler. A study conducted by the institute of national medical research in Canada which involved a large multicenter survey being filled out by patients who have been appointed Turbuhalers by hospitals all across Canada. This survey was conducted in order to see what errors and limitations are associated with the use of Turbuhalers from the patients perspectives. The results are mostly a reflection of poor technique. It is also important to note that before the survey was conducted the patients were taught and reminded on how to correctly use the inhaler. This meant that patients were able to detect errors in their own techniques while filling out the survey (Joseph 1999). From the survey it was found that only 72% of the patients held the Turbuhaler upright during loading while the remainder loaded the device incorrectly. Furthermore, it was found that 24% of Patients have been found not to inhale into the device forcefully enough thus are not able to acquire the full benefit of the medication as there is not enough concentration of it being extracted from the inhaler and breathed in. This is mostly due to confusion caused during the operation process both during loading and actual use as its not a simple procedure. Lack of provider knowledge adds to this problem (Joseph 1999).

A big concern by many users is the lack of tolerance Turbuhalers and DPIs in general have towards liquids. The humidity normally enters the inhaler via ambient air or more directly from patients exhaling into the mouth piece. It was established from the results of the survey that on average 20% of patients exhale into the mouthpiece. The design of Turbuhalers influences the effect of humidity, as it contains multi dose reservoirs which are more vulnerable as there is no protection around the powdered drug such as that in capsules or blister packs which adds to the problem. It has been found that the effects of ambient air on the Turbuhaler within 2hours after exposure to this air reduced the amount of drug released to 40% of its normal quantity. This reduction lasted for a period of 4 days starting from the time of initial exposure and it was ensured that there was no further exposure. The graph in figure x gives a visual representation of results obtained during a similar procedure conducted but the difference here was continuous exposure to high ambient humidity at 30oC and 75% relative humidity over a period of 8 weeks. Humidity conditions were designed to match conditions when using a Turbuhaler in a Bathroom. The measurement made in this scenario is the percentage decrease of fine particle mass due to the effects of the introduced humidity (Joseph 1999).

Figure 2: Effects of Humidity on the fine particle mass over a period of 8 weeks

The graph clearly indicates a gradual decrease in fine particle mass over the period of 8 weeks. It is essential for optimum function that the drug located within the Turbuhaler consists of pure fine powder. This is because only powder particles are small enough to travel through the inhaler without causing blockages. Therefore if fluid enters the inhaler the patient may find it difficult to inhale through the device and would ultimately result in the inhaler not functioning properly. The type of drug used also influances the effect umidity would have if introduced into the inhaler. This is because some powder react differently when exposed to humidity. Some drugs have shown greater adhesion between powder particles and therfore reduced particle mass as humidity increases. While some drugs show decreased adhesion with higher

humidity due to having electro static forces. For this reason humidity has the effect in causing a varaince in delivery from DPIs with different drugs (Joseph 1999). Other disadvantges associated with the use of turbuhalers is that there is no definate guide as to when the inhaler is empty. As there is not taste of the drug some patients continue to use the inhaler in the abscence of the medication without realsiing this. Additionally, some patients are not able to produce required flow rate so are unable to use device (UHN 2011)

Ways to overcome problems

By obtaining knowledge with regards to the problems associated with the use of Turbuhalers, this makes it easier to recognise different techniques that can be used to overcome these problems. Research conducted in this matter shows that in many cases that its not the actual device that influances errors from occuring rather the problems and erros that happen is by the handler of the device. This is mostly due to poor technique implemented caused mainly by lack of knoweldge on how the device functions. For this reason, a way to overcome this problem is through careful tution by the prescriber of the drug. Extra resources should be given such as videos to help remind the patient on how to use the device correctly even after tution. Instructions that come with the device, usually found in the packaging, should be in a format were the patient can easily understand and follow the procedure. It is also important to inform the patient of the potential problems that are associated with the incorrecte use of the inhaler to further encourage user to implement correct techniques (Andrew 2012). A major error related to the actual design of the Turbuhaler is that some turbuhalers do not indicate when the device has no more medication present. This problem can be overcome by using a different type of turbuhaler that has a dose indicator present. The way it works is that a red mark appears once there is approximately 20 doses remaininng. This would allow time to either replace the inhaler or refill the inhaler with the drug (Andrew 2012). Futhermore, it is important that no liquid enters the turbuhaler as this would considerably reduce the efficieny of the device to such an extent were it would required to replace. To prevent this from happening patients need to be taught to ensure that they do not exhale into the device or even use liquieds in a close viscinity from the device unless the plastic cover is placed onto the device.

Conclusion
Turbuhalers have benifited in helping to treat many individual regardless of how severe their conditions may be. This is because a very low flow rate is required to be produced during inhalation to deliver the drug to the patient. Through research conducted it was foud that only a very small percentage of people would find it difficult to use this inhaler as they were unable to produce the required flow rate during inhalation while 98% still managed to produce the required flow rate even while suffering from accute asthma. The simplicity of the

design and the procedure required to load the device is a reason to why many choose to use this inhaler. Its also a much safer option to use this device and most importantly it has no side effects. The instructions required to follow to have a successfull delivery of the medication are not complicated and are easy to achieve. Nevertheless, studies have shown that people still are using this device in a incorrect manner and therfore can not fully benefit by using the device. Therfore, more information needs to be provided to the patients to ensure they do not make erros while operating the device. A major problem associated with the use of this device is the lack of tolerance it has towards liquids as it causes blockages within the system. Extra care must therfore be taken to ensure no liquid enters the Turbuhaler.

Referances
C.Kumaresan. (2006). Dry Powder Inhaler - Formulation aspects. Inhalers. 2 (1), p15-19. H. Bisgaard. (2001). Fine particle mass from the Diskus inhaler and Turbuhaler inhaler in children with asthma. European Respiratory journal. 3 (3), p4 The Ohio State University. (2009). Turbuhaler Dry Powder Inhaler (DPI).Available: https://patienteducation.osumc.edu/Documents/turbuhaler-dpi.pdf. Last accessed 15/04/2013 Smith.A. (2002). Turbuhalers and their application. Inhalers. 5 (2), p5-7 Daniella.B (2012). USING INHALATION DEVICES. Cambridge: McGraw-Hill. p80-140. Nesbitt.S. (2006). Medication Devices. Available: http://www.bcdecker.com/SampleOfChapter/1-009-174-3.pdf. Last accessed 24/04/2013 Prat.B. (2008). Lung delivery of salbutamol by dry powder inhaler (Turbuhaler) and small volume antistatic metal spacer (Airomir CFC-free MDI plus NebuChamber). Inhaler Devices. 3 (1), p11-12 Brown.PH. (1995). Peak inspiratory flow through Turbuhaler in acute asthma.. Treating Asthma. 1 (2), p3-9. ehow. (2008). How Much Air Can Your Lungs http://www.ehow.com/about_5466024_much-air-can-lungs-hold.html. 30/04/2013 Hold?. Available: Last accessed

UHN. (2011). Asthma and Airway Centre Medication. Available: http://www.uhn.ca/Clinics_&_Services/services/asthma/medication/common_advantages.asp. Last accessed 30/04/2013 Joseph L Rau (1999). Practical Problems With Inhalers. London: FAARC. p200-260. Andrew.P. (2012). Turbuhalers application: Advantages and Disadvantages. Turbuhalers DPI. 1 (5), p3-8