Polymer coating of carrier excipients modify aerosol performance of adhered drugs used in dry powder inhalation therapy.

The potential of excipient coating to enhance aerosol performance of micronized drugs in carrier excipient-drug blends, used in dry powder inhalers, was investigated. Both EC (ethyl cellulose) and PVP (polyvinylpyrrolidone) were used as coating agents. Carriers were prepared via sieve fractioning followed by spray drying, with and without polymer additive.

Preparation and evaluation of single and co-engineered combination inhalation carrier formulations for the treatment of asthma.

Two combination dry powder inhalation formulations were engineered via spray drying and co-spray drying salbutamol base (SB) and beclomethasone dipropionate (BDP). The aerosol performances of the individual drugs, a physical mix and the co-spray-dried particle systems were investigated after blending with conventional lactose carrier, under realistic dose regimes. Furthermore, each system was evaluated in terms of the physicochemical properties and via high-throughput Raman microscopy (to study co-association and deposition patterns after in vitro aerosolisation studies).

Co-deposition of a triple therapy drug formulation for the treatment of chronic obstructive pulmonary disease using solution-based pressurised metered dose inhalers.

Objectives: The formulation of multi-drug pressurised metered dose inhalers (pMDIs) opens up exciting therapeutic opportunities for the treatment of asthma and chronic obstructive pulmonary disease (COPD). We have investigated the formulation of a solution-based triple therapy pMDI containing ipratropium, formoterol, budesonide and ethanol as co-solvent.

Methods: This system was characterised for in-vitro performance and compared with marketed pMDIs (Atrovent and Symbicort).

Co-spray-dried mannitol-ciprofloxacin dry powder inhaler formulation for cystic fibrosis and chronic obstructive pulmonary disease.

The aim of this study was to assess the potential of delivering a combination therapy, containing mannitol (a sugar alcohol with osmotic characteristics), and ciprofloxacin hydrochloride (an antibacterial fluoroquinolone), as a dry powder inhaler (DPI) formulation for inhalation. Single and combination powders were produced by spray drying ciprofloxacin and mannitol, from aqueous solution, at different ratios and under controlled conditions, as to obtain similar particle size distributions. Each formulation was characterised using laser diffraction, scanning electron microscopy, differential scanning calorimetry, dynamic vapour sorption, X-ray powder diffraction, and colloidal force microscopy.

Can low-dose combination products for inhalation be formulated in single crystalline particles?

This study aims to produce and test the performance of novel crystalline respirable particles containing two low-dose active ingredients and mannitol. This technique overcomes the usual requirement of blending with lactose carriers in formulating combination inhalation products. Ternary powders were produced by co-spray drying solutions containing an inhaled corticosteroid (ICS), a long-acting beta2-agonist (LABA), and mannitol as a crystalline excipient.

A novel method for the production of crystalline micronised particles.

The aim of this study was to develop a method for converting an amorphous drug to a crystalline form to enhance its stability and inhalation performance. Spray-dried amorphous salbutamol sulphate powder was conditioned with supercritical carbon dioxide (scCO(2)) modified with menthol. The effect of menthol concentration, pressure, temperature and time on the characteristics of the resulting salbutamol sulphate powder was investigated.

Does electrostatic charge affect powder aerosolisation?

To study if electrostatic charge initially present in mannitol powder plays a role in the generation of aerosols, mannitol was unipolarly charged to varying magnitudes by tumbling the powder inside containers of different materials. The resulting charge in the powder was consistent with predictions from the triboelectric charging theories, based on the work function values from literature and electron transfer tendencies from measurement of contact angle. The latter generated a parameter, gamma(-)/gamma+, which is a measure of the electron-donating capacity relative to the electron-accepting tendency of material.

Controlled release antibiotics for dry powder lung delivery.

Introduction: Two controlled release (CR) antibiotics intended for inhalation therapy were evaluated.

Material And Methods: Ciprofloxacin and doxycycline (both hydrochlorides) were selected as model drugs. Microparticles containing 90:10 ratio of polyvinyl alcohol (PVA) and single antibiotics or combinations were obtained via spray drying.

Pulmonary spray dried powders of tobramycin containing sodium stearate to improve aerosolization efficiency.

Purpose: Tobramycin microparticulate powders containing the hydrophobic adjunct sodium stearate were studied for their use as pulmonary formulations in dry powder inhalers.

Methods: Spray-dried powders were characterized in terms of particle size distribution, morphology, crystallinity, drug dissolution rate, toxicity on epithelial lung cells and aerosol efficiency.

Results: The presence of the sodium stearate had a direct influence on the aerosol performance of tobramycin spray-dried powders.

Lactose composite carriers for respiratory delivery.

Purpose: Lactose dry powder inhaler (DPI) carriers, constructed of smaller sub units (composite carriers), were evaluated to assess their potential for minimising drug-carrier adhesion, variability in drug-carrier forces and influence on drug aerosol performance from carrier-drug blends.

Methods: Lactose carrier particles were prepared by fusing sub units of lactose (either 2, 6 or 10 microm) in saturated lactose slurry. The resultant composite particles, as well as supplied lactose, were sieve fractioned to obtain a 63-90 microm carriers.

Influence of the polydispersity of the added fine lactose on the dispersion of salmeterol xinafoate from mixtures for inhalation.

The purpose of this study was to determine and understand the effect of the polydispersity of fine lactose (FL) on the dispersion of salmeterol xinafoate (SX) from SX-coarse lactose mixtures for inhalation. SX mixtures were prepared using validated laboratory mixing. The in vitro deposition of SX was measured using a twin-stage impinger and SX analysed using high performance liquid chromatography.

Scanning white-light interferometry as a novel technique to quantify the surface roughness of micron-sized particles for inhalation.

A novel approach of measuring the surface roughness of spherical and flat micron-sized drug particles using scanning white-light interferometry was applied to investigate the surface morphology of micron-sized active pharmaceutical ingredients (APIs) and excipient particles used for inhalation aerosols. Bovine serum albumin (BSA) and alpha-lactose monohydrate particles were chosen as model API and excipient particles, respectively. Both BSA and lactose particles were prepared with different degrees of surface corrugation using either controlled spray drying (four samples of BSA) or decantation (two samples of lactose).

Micro-particle corrugation, adhesion and inhalation aerosol efficiency.

Atomic force microscopy (AFM) was used to evaluate the particle adhesion and surface morphology of engineered particles for dry powder inhaler (DPI) respiratory therapy to gain a greater understanding of interparticle forces and the aerosolisation process. A series of spherical model drug particles of bovine serum albumin (BSA) was prepared with different degrees of surface corrugation. The particles were evaluated in terms of particle size (laser diffraction) and microscopic morphology (scanning electron microscopy).

Role of agglomeration in the dispersion of salmeterol xinafoate from mixtures for inhalation with differing drug to fine lactose ratios.

The purpose of this study was to characterise the role of agglomeration on salmeterol xinafoate (SX) dispersion from mixtures for inhalation by varying the SX concentration and the proportion of fine lactose (FL). SX concentrations and SX:FL ratios ranged from 1.0% to 5.

Cospray dried antibiotics for dry powder lung delivery.

The aim of this study was to assess the potential of delivering a combination antibiotic therapy, containing doxycycline and ciprofloxacin (both hydrochloride) as a dry powder (DPI) formulation for inhalation. Single and combination antibiotics were produced by spray drying. Particle size distributions were characterized by laser diffraction and imaging conducted by scanning electron microscopy.

The influence of drug morphology on aerosolisation efficiency of dry powder inhaler formulations.

The physicochemical properties of two forms of spray dried bovine serum albumin (BSA) have been investigated using particle sizing, surface energy measurement, atomic force microscopy (AFM) and colloid probe microscopy. The BSA powder had similar particle size distributions and surface energy but significantly different morphologies and roughness, classified as smooth and corrugated BSA. Adhesion forces between the corrugated BSA and alpha-lactose monohydrate indicated median adhesion forces were significantly less than for smooth/carrier interaction forces.

Adhesion and redistribution of salmeterol xinafoate particles in sugar-based mixtures for inhalation.

The aim of this study was to evaluate coarse and fine sugars as potential alternative excipients in dry powder inhalation formulations and to develop a greater understanding of the key interactions between the particulate species in these mixtures. Interactive mixtures composed of salmeterol xinafoate (SX) and different type of sugars (lactose, glucose, mannitol and sorbitol) were prepared using validated laboratory scale mixing. The sugars and SX were characterised by laser diffraction, scanning electron microscopy, atomic force microscopy and loss on drying method.

Agglomerate strength and dispersion of salmeterol xinafoate from powder mixtures for inhalation.

Purpose: The study investigated the role of agglomeration and the effect of fine lactose size on the dispersion of salmeterol xinafoate (SX) from SX-lactose mixtures for inhalation.

Methods: Particle size distributions were characterised by Malvern Mastersizer S, Aerosizer and Spraytec, and imaging conducted by scanning electron microscopy (SEM). Inter-particulate adhesion was quantified by atomic force microscopy.