Fine particles dose

Many studies present and discuss in vitro and in vivo drug deposition resnlts obtained with inhalation systems. It is often difficult to compare in vitro results from different studies, because different testing equipment and different definitions for the fine particle dose may have been used. 

Wilkes W, Fink J, Dhand R. Selecting an accessory device with a metered-dose inhaler variable influence of accessory devices on fine particle dose, throat deposition, and drug delivery with asynchronous actuation from a metered-dose inhaler. J Aerosol Med 2001 14(3)251-360. 

Fine particle dose The amount of drug with particle diameter less than 5.0 pm, which is a portion of the inhaled dose... 

Figure 2 Relationship between deposition of a radiolabeled DPI aerosol and the measured fine particle dose of the labeled powder inhaled for each subject. Both variables are expressed as the percent of nominal dose. The correlation is higher for the lower flow rate used to inhale the powder, possibly due to the more consistent amount of drug deposited in the oropharynx. (From Ref. 88.)...

Olsson B, Asking L, Borgstrom L, Bondesson E. Effect of inlet throat on the correlation between measured fine particle dose and lung deposition. In Dalby RN, Byron PR, Farr SJ, eds. Respiratory Drug Delivery V. Buffalo Grove, IL Interpharm Press, 1996 273-281. 

Device design often commences with the aerosolisation mechanism, since the fine particle dose reaching the lung is the critical therapeutic dose. This is often a crude mechanism to show proof of principle. However, for regulatory constraints, the metering system is more important, and this is often given insufficient attention in the early stages of a project. 

In optimising the product, both device and formulation are modified, and the normal product release tests are evaluated. Extra investigations are also carried out, such as a standard drop test to ensure that the device is robust. Other major areas for investigation are the dependence of fine particle dose on airflow rate (Srichana et al. 1998), the effect of humidity both on storage (Naini et al. 1998), Maggi et al. 1999) and in-use, drug retention within the device, the effect of orientation and electrostatics (Carter et al. 1998). 

Fine Particle Fraction and Fine Particle Dose... 

Incorrect handling affects the efficacy of the treatment to a lesser extent than noncompliance. For example, in vitro studies have shown that omission to shake the pMDI before use reduced total and fine particle dose by 25 and 36%, respectively, while two actuations separated by 1 s decreased fine particle dose by 16% (13). The same authors also demonstrated that storing the pMDI stem... 

Nominal dose Metered dose Delivered dose Fine particle dose Retained amount Inhaled dose Exhaled amount Recovered amount ... 

Impaction accounts for most of the large particle trap effect of the spacer. This is illustrated in Fig. 4, which shows the fine and coarse particle doses obtained from a budesonide pMDI (Pulmicort, AstraZeneca, Sweden) actuated into a metal spacer. The spacer was initially 23 cm long, and subsequent reduction in the length of the spacer caused a reduction in both the coarse- and eventually also the fine-particle doses. Even the initial shortening of the spacer reduced the coarse particle dose, whereas the fine-particle dose was unaffected thus, the total particle dose was reduced, but the ratio between fine and coarse particles was improved by shortening the spacer. Thus, the spacer length is critical for the fine-particle dose and the ratio of fine to coarse particles. Different pMDIs have different vapor pressures and therefore different aerosol velocities and volumes as a result, the optimal spacer length is specific to a particular pMDI. Moreover, the spacer should be adapted to the particular aerosol jet. For this reason, the op-... 

Similar differences have been described among other spacers. The fine particle dose varied by twofold between commonly used universal plastic spacers (45). 

Another aspect is the humidity of the air at inhalation. Humidity at inhalation may lead to an increase in the adhesion between the dry-powder particles. In general it can be stated that inhalation at a very high relative humidity will tend to decrease the fine particle dose from a DPI (61,62), although there was no difference in clinical effect between a salbutamol DPI (Turbuhaler) and pMDI in hot, humid regions (63). 

Asking L, L66f T, Pettersson G. Flutide Diskus less consistent than Pulmicort Tur-buhaler with respect to in vitro fine particle dose proportionality. Am 1 Respir Grit Care Med 2001 Accepted. 

Detection with MS is particularly important for the isolation of compounds that lack useful chromophores or are found only in complicated mixtures such as lactose [56]. The lack of a UV-absorbing chromophore in the saccharide structure limits the mode of detection. Refractive index detection requires precise control of the mobile phase and often does not meet the demands of trace-level analysis needed concerning sensitivity and selectivity. Even chemical derivatization, for example, postcolumn derivatization and enzymatic derivatization, which greatly improves the selectivity and sensitivity of a chromatographic detection systan, does not meet the needed trace levels for the detection of the fine particle dose of lactose. The reason... 

The two main determinants for medicine deposition in the respiratory tract are the aerodynamic size distribution of the aerosol and the manoeuvre with which the aerosol is inhaled. They govern the mechanisms that are respraisible for particle deposition in the lungs. By varying the inhalation manoeuvre, not only the distribution in the airways for the same aerosol is changed in many cases also the amount and properties of the delivered fine particle dose are affected. The complex interplay between inhalation manoeuvre, aerosol properties and site of deposition has led to many misconceptions regarding the best inhaler choice for individual patients and the way these inhalers need to be operated to achieve optimal therapy for the patient. In this chapter the medicine deposition mechanisms for inhaled aerosols are explained as functions of the variables involved. In addition, the working principles of different inhaler types are described and it is discussed how their performance depends on many inhalation variables. Finally, some persistent misconceptions in the literature about the most preferable dry powder inhaler properties and performance are umaveUed. 

Important for aU different preparations and delivery devices is that they meet the requirements for uniformity of the delivered dose and the number of deliveries per inhaler for multidose inhalers. Also the fine particle dose has to be tested and calculated, but there are no... 

Fine Particle Dose (FPD) and Fine Particle Fraction (FPF)... 

The MMAD is a parameter frequently used to characterise therapeutic aerosols. MMAD alone is not very useful however, as it provides no information about the size distribution in the aerosol and the mass fraction of the dose (label claim) processed into a suitable aerosol. Fine particle dose and fraction are more meaningful parameters, particularly for DPIs (see definitions). 

---