The novel approach provides a fundamental insight into the cohesive-adhesive balances in dry powder formulations and further understanding of powder behavior.

No abstract

The use of the colloid Atomic Force Microscrope (AFM) technique in combination with the cohesive-adhesive balance (CAB) system provides a novel preformulation tool for investigating the likely behavior of a dry powder formulation and a possible means of interpreting the possible de-aggregation and dispersion mechanisms of carrier-based formulations.

The aim of the study was to investigate the specific inf luence of force control agents (FCAs) (leucine, lecithin and magnesium stearate) on the interfacial properties of a salbutamol sulphatelactose dry powder inhaler formulation. The inf luence of FCAs on the cohesive and adhesive force balance was directly assessed via an atomic force microscopy (AFM) colloid probe technique, with a recently developed cohesive-adhesive balance (CAB) graphical analysis procedure. Coprocessing of constituent particles was conducted by a novel dry mechanical fusion method (Mechanofusion). The in vitro deposition profile of the model salbutamol sulphate formulations was investigated using a Monohaler ® DPI device with a next generation impactor (NGI) apparatus. The CAB-graph analysis of a salbutamol sulphate-lactose binary system suggested a predisposition for an interactive mixture. However, the reduced intermixing coefficient (F drug-lactose /F drug-drug ) suggested that a significant amount of energy would be required to overcome the strong adhesive interaction for efficient dispersion of the drug from a lactose surface. The processing of lactose with leucine, lecithin or magnesium stearate, prior to formulating with the drug, significantly reduced the adhesive interactions of the salbutamol with modified lactose samples. The CAB analyses indicated that the reduced intermixing coefficients shifted to such an extent that cohesive drug interactions dominated. These dramatic shifts in the balance of forces were shown to lead to poor blend homogeneity and potential for significant segregation between drug and carrier particles. Conversely, the conditioning of salbutamol sulphate with leucine, lecithin and magnesium stearate, which modified both the adhesive and cohesive interactions, formed homogenous interactive blends with advantageously weaker drug-lactose interactions. Formulations with pre-conditioned drug, in contrast to conditioned lactose, offered the best drug delivery performances. The use of the colloid AFM technique in combination with the cohesive-adhesive balance (CAB) approach provided a very accurate means of predicting dry powder formulation behaviour and the specific inf luence of particulate interactions on aerosol performance.

Allergen-induced inhibition of pulmonary surfactant in asthma may promote airway oedema and consequently potentiate the severity of the asthmatic response. A randomised, single-blind, cross-over study of an inhaled synthetic phospholipid dry-powder surfactant (Pumactant) was conducted in atopic, asthmatic subjects with previously documented early and late asthmatic responses (EAR and LAR) to an inhaled allergen. This was conducted to evaluate the role of exogenous surfactant administration on EAR and LAR. A total of seven subjects had complete evaluable data and received the full dose of Pumactant.Asthmatic subjects inhaled two separate doses of 400 mg Pumactant prior to an allergen exposure. The first dose was administered 8 h in advance and the second dose 30 min in advance. The dosage occurred through a purpose-built administration device. This was followed by a standard bronchial-provocation test, and forced expiratory volume in one second (FEV1) was measured at regular intervals over a 10-h period.Pumactant was well tolerated and, surprisingly, abolished the EAR but not the LAR in all seven subjects. The mean area under the curve between 0-2 h (EAR) following bronchial provocation test was 0.08 for the Pumactant treatment group (PT) and 13.29 for the no treatment (NT) group. The maximum drop in FEV1 for EAR was 4.19% and 23.98% in the PT and the NT group, respectively.The demonstration of inhibition of the early asthmatic response by exogenous surfactant, provides the first evidence that pulmonary surfactant dysfunction may also contribute to the very early asthmatic response to allergen. Exogenous surfactant administration could serve as a useful adjunct in controlling the early allergen-induced symptoms in patients with allergic asthma.