Inhaleables dispersible formulations

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. 

Sprays Medicated liquids prepared for dispersal by atomizers or nebulizers, usually on external surface or mucous membranes of the respiratory tract. In the United States Pharmacopoeia, sprays were called inhalatio the National Formulary referred to them as nebulae. Sprays of the early twentieth century were formulated with aromatics dissolved in light mineral oil. As injuries from inhaled oils became apparent, especially among children, these sprays were displaced by buffered aqueous solutions. ... 

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. 

In aerosols, other than those for inhalation, colloidal silicon dioxide is used to promote particulate suspension, eliminate hard settling, and minimize the clogging of spray nozzles. Colloidal silicon dioxide is also used as a tablet disintegrant and as an adsorbent dispersing agent for liquids in powders. Colloidal silicon dioxide is frequently added to suppository formulations containing lipophilic excipients to increase... 

Tetrafluoroethane is a hydrofluorocarbon (HFC) or hydro-fluoroalkane (HFA) aerosol propellant (contains hydrogen, fluorine, and carbon) as contrasted to a CFC (chlorine, fluorine, and carbon). The lack of chlorine in the molecule and the presence of hydrogen reduces the ozone depletion activity to practically zero. Hence tetrafluoroethane can be considered as an alternative to CFCs in the formulation of metered-dose inhalers (MDIs). It has replaced CFC-12 as a refrigerant since it has essentially the same vapor pressure. Its very low Kauri-butanol value and solubility parameter indicate that it is not a good solvent for the commonly used surfactants for MDIs. Sorbitan trioleate, sorbitan sesquioleate, oleic acid, and soya lecithin show limited solubility in tetrafluoroethane and the amount of surfactant that actually dissolves may not be sufficient to keep a drug readily dispersed. 

Key parameters are different for different routes of delivery and different formulations particle size is a key factor in inhalation products and in topical preparations where the dmg is dispersed rather than dissolved in the vehicle. 

In particular, the loose packing of particles promotes an open powder structure that is less adhesive and flows and disperses more readily. There is a strong correlation between the interaction parameters derived by IGC and the in vitro data that play an important role in the prediction of aerosol performance of dry powder inhalation formulations. Enhanced dispersibility is particularly important for DPI devices, where performance strongly depends on powder deaggregation at relatively low dispersion forces. Clearly, high turbulence is preferable for dispersion, but it inevitably leads to high pressure differentials, which may prevent many devices from functioning correctly. In addition, low dispersion forces for supercritically produced... 

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