Inhaled drug formulations

Norwood, D.L. Prime, D. Downey, B.P. Creasey, J. Satinder, S.K. Haywood, P. Analysis of polycyclic aromatic hydrocarbons in metered dose inhaler drug formulations by isotope dilution gas chromatography/ mass spectrometry. J. Pharm. Biomed. Anal. 1995, 13 (3), 293-304. 

Thus the prediction showed that FP (-11.5 kcal/mol) has the highest cohesive strength when compared to BUD (-9.9 kcal/mol) or SB (-7.8 kcal/mol) and this ranking correlated well to the laser diffraction measurements where the airflow pressure required for complete dispersion (CPP) was 3.5, 2.0 and 1.0 Bar for FP, BUD and SB, respectively. This case study demonstrates that the technologies also have the potential to be used as predictive tools for assessing the cohesive-adhesive strength balance for inhaled drug formulations. 

S. Onoue, et al. New treatments for chronic obstructive pulmonary disease and viable for-mulation/device options for inhalation therapy. Expert Opin DrugDeliv 6,793-811,2009. B.M. Ibrahim, et al. Challenges and advances in the development of inhalable drug formulations for cystic fibrosis lung disease. Expert Opin DrugDeliv 8, 451-466, 2011. 

Besides the inhalative use, the development of a drug formulation for A9-THC has to address other bioavailabihty questions. A major problem is the hpophiUcity and poor solubiUty in water, hmiting oral uptake when given orally. Because of this, other parenteral routes of apphcation are imder investigation like puhnonal uptake by vaporization, subUngual or intranasal administration, and apphcation by injection of A9-THC incorporated in hpo-somes. 

The following sections provide an overview of the application of the IPL for the study of drug absorption. Examples are provided to illustrate the use of the IPL to study drug permeability, absorption profiles, transport mechanisms and the effects of inhaled dose formulation on drug disposition. 

It is important to consider the impact of different formulations. The requirements for an inhaled drug, for example, will be quite different from the requirements for the same drug given orally. 

Several inhaled drugs are used for the relief and management of asthma. The drug, formulated into a solution which can be reduced to fine particles, is inhaled from an inhaler device and most patients over the age of about 6 years can be trained to use the device so as to get an effective dose into the bronchial tree. How far does the drug go Studies have shown... 

Labiris NR, Dolovich MB. Pulmonary drug delivery. Part II the role of inhalant delivery devices and drug formulations in therapeutic effectiveness of aerosolized medications. Br J Clin Pharmacol 2003 56(6) 600-12. 

Even when the appropriate inhaler is chosen, the influence of the disease state cannot be ignored. Disease states can influence the dimension and properties of the airways and hence the disposition of any inhaled drug. Thus, great care must be taken when extrapolating the findings based on intratracheal administration to different animal species in order to predict deposition profiles after inhalation of aerosol formulations by patients suffering from airway disease. DPIs are not appropriate in many diseases when the ability to have sufficient airflow is hindered. Since many diseases that we would like to treat via pulmonary administration of biomolecules cause a decrease in airflow, we must be careful in the decision of which type of inhalation mechanism to choose. 

Nebulizers are devices for converting aqueous solutions or micronized suspensions of drag into an aerosol for inhalation, although the drug formulations are, wherever possible, aqueous solutions. Selection of appropriate salts and pH adjustment will usually permit the desired concentration to be achieved. If this is... 

Parameters that most influence the behavior of a spray are the viscosity, the thixotropy, the surface tension, and the density. Modification of the swirl chamber and the inlet channels makes it possible to adjust the spray performance to the patient s requirements (Fig. 3). The particle size distribution can be altered by varying the dimensions and the geometry of the orifice, as well as the pressure build-up in the volume chamber prior to dispensing. One of the major criteria is to keep the fraction of extremely small particles very low to avoid partial inhalation of the drug formulation. 

Dry powder preparation and formulation are only part of the inhalation drug delivery system. Dispersion of these powders is closely linked to the performance of the inhaler device. 

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