Dry powder antibiotics for inhaled anti-tuberculosis therapy

textThe aim of this research was to develop and fully investigate a novel method of antibiotic drug delivery to the lung that will address problems with current therapeutic regimens for treatment of airway infections. To demonstrate the performance of prepared formulations, the design of suitable characterization methods were also aimed. A novel dissolution method for evaluating the in vitro dissolution behavior of inhalation formulations was developed. The membrane holder was designed to enclose previously air-classified formulations so that they could be uniformly tested in the dissolution apparatus. Dissolution procedures, the apparatus, the dose collection, the medium, and test conditions were developed and the dissolution behaviors of test compounds were evaluated by experimental and mathematical analysis. It was proved that the aerodynamic separation of formulation prior to dissolution assessment have a significant influence on the dissolution profiles. The optimized test method using the membrane holder was applied to evaluate in vitro dissolution profiles of the manufactured formulations of rifampicin (RF). The carrier/excipient-free RF dry powder formulation was investigated. The rifampicin dihydrate (RFDH) powders having MMAD of 2.2 um were prepared using a simple recrystallization process. The RFDH powders have a thin flaky structure, and this unique morphology provides improved aerosolization properties at maximal API loading. The manufactured RFDH formulation showed 80% drug release within 2 hours. To retard the release rate of RF, the prepared RFDH crystals were coated with hydrophobic polymer, PLA or PLGA, using spray-dryer equipped with multi-channel spray nozzles. The multi-channel spray nozzle used in this study has two separate nozzles for aqueous solution and one for gas fluid. The RFDH crystals and the coating solutions were sprayed through the two separate liquid nozzles at the same time. The coated RFDH formulations were prepared using multi-channel spray nozzles. The coated formulations contained at least 50% w/w of RF with no change of their flaky morphology. The initial RF release was lowered by coating; the lowest initial RF release was observed from the coated powders with PLA polymer as 32% among the coated formulations. Overall, the 80% of RF was released within 8 hours. The RFDH and coated RFDH formulations delivered via the pulmonary route would be anticipated to provide higher local (lung) drug concentrations than that of orally delivered powders. Particularly, the coated RFDH powders deposited in the alveolar region may prolong the drug residence time in the site of infections. Additionally, it was proved that the RFDH and coated RFDH formulations provided much better stability than the amorphous RF.Pharmac

Optimizing Spray-Dried Porous Particles for High Dose Delivery with a Portable Dry Powder Inhaler

This manuscript critically reviews the design and delivery of spray-dried particles for the achievement of high total lung doses (TLD) with a portable dry powder inhaler. We introduce a new metric termed the product density, which is simply the TLD of a drug divided by the volume of the receptacle it is contained within. The product density is given by the product of three terms: the packing density (the mass of powder divided by the volume of the receptacle), the drug loading (the mass of drug divided by the mass of powder), and the aerosol performance (the TLD divided by the mass of drug). This manuscript discusses strategies for maximizing each of these terms. Spray drying at low drying rates with small amounts of a shell-forming excipient (low Peclet number) leads to the formation of higher density particles with high packing densities. This enables ultrahigh TLD (>100 mg of drug) to be achieved from a single receptacle. The emptying of powder from capsules is directly proportional to the mass of powder in the receptacle, requiring an inhaled volume of about 1 L for fill masses between 40 and 50 mg and up to 3.2 L for a fill mass of 150 mg

Organometallic Iridium(III) Complex Sensitized Ternary Hybrid Photocatalyst for CO2 to CO Conversion

A series of heteroleptic iridium(III) complexes functionalized with two phosphonic acid (-PO3H2) groups ((IrP)-Ir-dfppy, (IrP)-Ir-ppy, (IrP)-Ir-btp, and (IrP)-Ir-piq) were prepared and anchored onto rhenium(I) catalyst (ReP)-loaded TiO2 particles (TiO2/ReP) to build up a new IrP-sensitized TiO2 photocatalyst system (IrP/TiO2/ReP). The photosensitizing behavior of the IrP series was examined within the IrP/TiO2/ReP platform for the photocatalytic conversion of CO2 into CO. The four IrP-based ternary hybrids showed increased conversion activity and durability than that of the corresponding homo- (IrP+ReP) and heterogeneous (IrP+TiO2/ReP) mixed systems. Among the four IrP/TiO2/ReP photocatalysts, the low-energy-light (>500 nm) activated (IrP)-Ir-piq immobilized ternary system ((IrP)-Ir-piq/TiO2/ReP) exhibited the most durable conversion activity, giving a turnover number of >= 730 for 170 h. A similar kinetic feature observed through time-resolved photoluminescence measurements of both (IrP)-Ir-btp/TiO2 and TiO2-free (IrP)-Ir-btp films suggests that the net electron flow in the ternary hybrid proceeds dominantly through a reductive quenching mechanism, unlike the oxidative quenching route of typical dye/TiO2-based photolysis.11Nsciescopu