الفهرس 
Aim of the work and objectivesOnly 14 pages are availabe for public view
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Abstract
5. Summary
The present thesis is generally divided into three parts :
Part 1: in-vitro study for comparing the efficacy of three different spacers and two types of nebulizers during oxygen therapy .
Part 2: in-vivo study for determining the drug delivering efficacy of the tested devices to the lungs.
Part 3: ex-vivo study to identify the total emitted dose that a patient would have received by the tested devices
Salbutamol is a potent short acting β2-agonist which is recommended for the management of COPD by the GOLD guideline to be administered as needed to relieve symptoms. Nowadays, measurement of pulmonary drug deposition has gained a great importance in the contex of drug development. The available methods used for this purpose are simulated in-vitro studies and in-vivo pharmacokinetic methods which can together reflect the amount of inhaled drug.
In-vitro studies include the determination of aerodynamic particle distrubtion and total emitted dose are commonly used for quality control testing of inhaled products. While pharmacokinetic methods using either plasma or urine samples can predict the relative pulmonary drug delivery (the effective lung dose) and also the total systemic delivery.
While in pharmacokinetic studies, urinary salbutamol concentration is measured 30 minutes after dose inhalaton during the absorption lag time of swallowed drug portion so this measured concentration and the calculated amount would account for the drug fraction absorbed mainly from lungs and can be used as a meaningful measure of pulmonary deposition. (Hindle et al. 1992)
Hence the objectives were:
a)To compare the total emitted dose (TED) from different inhalation devices (nebulizers and spacers) during oxgen therapy.
b)To determine the aerodynamic characteristics of the emitted dose of salbutamol from inhalation devices (nebulizers and spacers) (Fine particle dose FPD, Fine particle fraction FPF and Mass median aerodynamic diameter MMAD)
c)To evaluate the effect of inhalation techniques on the lung and systemic bioavailability in patients receiving oxygen therapy following inhalation from different devices.
d)To compare the in-vivo (linked to ex-vivo) fate of nebulized salbutamol from different inhalation devices in patients receiving oxygen therapy.
In the invitro part of the study, the main focus was comparing the total emitted dose delivered by three different spacers (AeroChamber mini (MC ), AeroChamber vent (VC ) and Combihaler )and two different nebulizers ( Aerogon Solo (SOLO) and jet nebulizer (JN)) during oxygen delivery at a selected flow rate 5 L/min. And then providing a meaningful particle size characterization of the dose emitted by each tested device using Anderson cascade Impactor.
Looking at the total emitted dose (TED), the results of our study demonstrated that SOLO has delivered the highest salbutamol amount when compared to JN and three spacers tested (p<0.05). While both MC and VC deliver negligible amount of salbutamol. Shifting to particle size characterization , there is no significant difference between all tested devices concerning fine particle fraction (FPF ) and mean median aerodynamic diameter (MMAD) but SOLO shows the highest fine particle dose (FPD) (p<0.05) followed by Combihaler then JN while MC and VC have the lowest FPD but the difference between Combihaler, JN , MC and VC is not significant .
In the in-vivo part of the study, three devices were selected to be tested in this part based on their encouraging invitro results : SOLO , JN and Combihaler. Twelve patients ( range 40 -70 years , mean age of 53.7 years) with chronic obstructive pulmonary disease receiving oxygen therapy were enrolled in this study from the Beni-Suef Teaching Hospital, Faculty of Medicine, Beni-Suef University and the Hospital of Chest Diseases. Patient with moderate or severe renal impairement or those with systolic blood pressure less than 100 mmHg were excluded from the study.Each patient had received 1 ml of farcolin respiratory solution containing 5 mg salbutamol with each of three different devices except with Combihaler 2 puffs (100µg salbutamol/puff ) perceded nebulization of 1ml as these puffs thought to have preliminary bronchodilator effect, all during oxygen therapy through nasal cannula. Two urine samples are taken from each patient: the first one is the urine voided 30 minute from dose inhalation and the other one is the urine pooled to 24 hour after dose inhalation.
Filters interposed between the spacer and facemasks trapped any drug likely to be inhaled. The amount of salbutamol deposited on the filter was assayed by high performance liquid chromatography in ex-vivo study.