Pharmacodynamics of dry powder formulations of salbutamol for delivery by inhalation.

Background: Salbutamol is a β2-selective adrenoceptor agonist used as a bronchodilator. Delivery by inhalation has many advantages over oral dosage for the treatment of asthma. It offers rapid onset of action with low systemic side effects. Objective: Evaluate the relationship of in vitro particle size characteristics and pharmacodynamics of formulations of inhaled salbutamol dry powder. Methods: Three formulations contained micronized salbutamol and a lactose carrier with different size ranges (40-80, 20-40, and 10-20 μm for formulations 1, 2, and 3, respectively). Following formulation of the drug, resultant powders were characterized using scanning electron microscopy and the aerosolization performance determined using an Andersen Cascade Impactor analysis. A high-performance liquid chromatography method was used for measuring the salbutamol drug content. The in vivo pharmacodynamics of the formulations was monitored in 12 healthy and 12 asthmatic volunteers. Results: The percentage of the fine particle fractions (FPF) for formulations 1, 2, and 3 were 24.87±0.52%, 33.82±3.80%, and 41.50±2.86%, respectively. The mass median aerodynamic diameters (MMAD) were around 3 μm for all formulations. The pharmacodynamic parameters, forced vital capacity (FVC), forced expiratory volume in one second (FEV1) and mid expiratory flow (FEF25-75), were indices for evaluation of the bioavailability of the bronchodilatory drug. All formulations improved the FEF25-75 value in asthmatics, while FVC and FEV1 were not altered. Conclusion: The formulations of salbutamol dry powder aerosols with a fine lactose carrier produced a high deposition in the lower regions of the respiratory tract. Although the FEF25-75 value in asthmatics was improved, the value did not correlate well with the FPF of the salbutamol dry powder.

Stabilization of luteinizing hormone-releasing hormone in a dry powder formulation and its bioactivity.

Background: Luteinizing hormone-releasing hormone (LHRH) is a naturally occurring hormone that controls sexhormones in both men and women. In general, LHRH is poorly absorbed through the gastrointestinal tract due to its large molecular size, high polarity, and loss from enzymatic degradation. Objective: Prepare and develop LHRH in a dry power formulation with stability and biological activity. Methods: Mannitol (M) and glycine (G) were chosen as ingredients to stabilize and protect LHRH during the freeze drying processes and during storage. The physicochemical properties of LHRH dry powders were examined by capillary electrophoresis, fluorescence spectrophotometry, scanning electron microscopy, and photon correlation spectroscopy. The release of LHRH from the dry powder was carried out in dissolution apparatus. In addition, a rat model was employed to study the bioactivity of LHRH in the dry powder form. Results: The LHRH dry powder formulations using M and G in the ratios of 6:4 and 7:3 were more stable than other formulations. LHRH colloids containing M:G showed no aggregation after storage at 4°C for one month. The concentration of LHRH in the dry powder form was more stable than that of LHRH in solution form. All the LHRH dry powder formulations were instantly dissolved within 10 seconds in an aqueous medium. After the LHRH dry powder (13 mg) was reconstituted and administered intraperitoneally to male rats during a one-month period, the testosterone level in the plasma was significantly decreased compared with an untreated group (15.0±1.0 ng/mL, 15.0±1.0 ng/mL and 20.0±2.0 ng/mL for LHRH containing M:G; 6:4, 7:3, and 8:2, respectively, compared to the control of 35±2 ng/mL, p<0.05). Conclusion: The LHRH dry powder formulations had good physicochemical properties and bioactivity.