Biomedical subjects

Daniela Traini

Publications and source records attributed to Daniela Traini.

8 recordsLinked to original sources

PubMed2007

The use of organic vapor sorption to determine low levels of amorphous content in processed pharmaceutical powders.

Organic dynamic vapor sorption (organic-DVS) was used to characterize amorphous content in known amorphous-crystalline mixtures of lactose and salbutamol sulfate. N-octane was chosen as an apolar probe and measurements were carried out by exposing mixtures of each sample to partial pressures 0-90% p/p(0). A linear relationship between amorphous content and n-octane partial pressure was observed for both lactose and salbutamol sulfate with R(2) values of 0.992 and 0.999, respectively. In addition, the influence of sequential mechanical processing in a ball mill on the amorphous content in crystalline lactose was investigated. Cumulative milling times resulted in an exponential increase in amorphous content (using the linear relationship obtained for lactose), with a maximum amorphous content of 14% being induced after 60 min milling. In comparison, analysis of the 60 min mill time samples after exposure to 85% relative humidity suggested 0.00% amorphous content.

Albuterol↗

PubMed2006

In vitro investigation of drug particulates interactions and aerosol performance of pressurised metered dose inhalers.

PURPOSE: To determine a relationship between adhesive and cohesive inter-particulate forces of interactions and in vitro performance in pressurised metered dose inhalers (pMDIs) suspension formulations. METHODS: Interparticulate forces of salbutamol sulphate (SS), budesonide (BUD) and formoterol fumarate dihydrate (FFD) were investigated by in situ atomic force microscopy (AFM) in a model propellant 2H, 3H perfluoropentane (HPFP). Experimental data were analysed using the recently developed cohesive/adhesive analysis method (CAB) and compared with in vitro deposition performances in pMDIs systems using Andersen cascade impactor (ACI). RESULTS: The in vitro investigation suggested that the micronised drug materials had significantly different aerosolisation profiles when manufactured as single or combination formulations. In general, the greatest significant differences were observed between SS single drug and SS-BUD and SS-FFD combinations. Analysis of the in vitro performance for the SS only formulation suggested that the cohesive nature of SS (as predicted by the CAB and observed with AFM) led to tightly bound flocs that did not fully deaggregate upon aerosolisation. CONCLUSIONS: It is suggested that the relationship between interparticulate interactions and in vitro performance of pMDIs suspension systems, when compared to direct measurement of the adhesion/cohesion forces, indicated good correlation. This approach may be useful in expediting the development of pMDI formulation and predicting performance.

Adhesiveness↗

PubMed2006

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. Deposition of SX was measured using a twin stage impinger. SX was analysed using validated high-performance liquid chromatography method (r(2)=1.0, CV=0.4-1.0%). RESULTS: Addition of fine lactose with a volume median diameter (VMD) of 7.9 microm to a SX-lactose carrier and carrier-free mixture resulted in significantly better dispersion (16.8% for 20% added fine lactose) than fractions with VMD of 3.0, 17.7 and 33.3 microm (less than 9.1% for 20% fine lactose). Using the carrier-free mixtures, particle sizing of the aerosol cloud using the Spraytec, coupled with the application of the Aerosizer using differing dispersion energies and SEMs of the samples, indicated that an open packed, agglomerate structure improved SX dispersion. The highest extent of SX dispersion occurred when SX and fine lactose were detached from the surface, usually in the form of loose agglomerates. CONCLUSIONS: The outcomes of this research demonstrated how agglomerate structure influenced dispersion and the key role of fine lactose particle size in SX dispersion from mixtures for inhalation.

Administration, Inhalation↗

PubMed2005

Comparative study of erythritol and lactose monohydrate as carriers for inhalation: atomic force microscopy and in vitro correlation.

The adhesion of micronised salbutamol sulphate to two carrier excipients, lactose monohydrate and erythritol, was investigated using the atomic force microscope (AFM) colloid probe technique and correlated with their respective physico-mechanical properties and aerosolisation performance. The particle size, morphology and moisture sorption properties of the carriers were similar thereby allowing direct comparison of functionality. AFM force measurements (n = 1024 force curves) were obtained between salbutamol sulphate drug probes (n = 4) and the excipients, as 63-90 microm sieve fractions and atomically smooth crystals. In general, significant differences in drug adhesion to lactose monohydrate and erythritol were observed (ANOVA, p<0.05), with erythritol exhibiting relatively greater adhesiveness. A linear relationship between drug probe adhesion to lactose monohydrate and drug probe adhesion to erythritol was established with salbutamol sulphate-lactose monohydrate adhesion being 60-70% of that of the erythritol system. In vitro analysis suggested good correlation with the adhesion measurements. The aerosolisation of salbutamol sulphate from erythritol carrier particles was significantly less (ANOVA, p<0.05) than from lactose monohydrate, with a fine particle dose (<6.4 microm) of 41.9 +/- 7.4 microg and 24.9 +/- 3.1 microg for the lactose monohydrate and erythritol carriers, respectively (n = 3).

Administration, Inhalation↗

PubMed2005

Surface energy and interparticle forces correlations in model pMDI formulations.

PURPOSE: To compare experimental measurements of particle cohesion and adhesion forces in a model propellant with theoretical measurements of the interfacial free energy of particulate interactions; with the aim of characterizing suspension stability of pressurized metered dose inhalers (pMDIs). METHODS: Interparticulate forces of salbutamol sulfate, budesonide, and formoterol fumarate dihydrate were investigated by in situ atomic force microscopy (AFM) in a model propellant 2H,3H perfluoropentane. The surface thermodynamic properties were determined by contact angle (CA) and inverse gas chromatography (IGC). Experimental data were compared with theoretical work of adhesion/cohesion using a surface component approach (SCA), taking into account both dispersive and polar contributions of the surface free energy. RESULTS: Results indicated that the measured forces of interaction between particles in model propellant could not be accounted for by theoretical treatment of the dispersive surface free energies via CA and IGC. A correlation between theoretical work of adhesion/cohesion and AFM measurements was observed upon the introduction of the polar interfacial interactions within the SCA model. CONCLUSIONS: It is suggested that the polar contributions of the surface free energy measurements of particles may play a crucial role in particle interaction within propellant-based systems. Together with the application of a SCA model, this approach may be capable of predicting suspension stability of pMDI formulations.

Albuterol↗

PubMed2005

The influence of dose on the performance of dry powder inhalation systems.

The relationship between drug/lactose ratio and aerosolisation performance of conventional carrier based formulations was investigated using the twin stage impinger. A dose range of approximately 10-450 microg of drug in a 50 mg lactose carrier formulation was studied. Statistical differences in both the fine particle dose and fine particle fraction were observed across the dosage range (ANOVA, p<0.05). In general, no statistically significant difference (Fishers Pairwise, p<0.05) in fine particle dose was observed between drug levels of approximately 10 microg and 135 microg, whereas a linear decrease in fine particle fraction was observed across the same drug level range (R2=0.977). Increasing the dose from approximately 135 microg to 450 microg resulted in a statistically significant increase in both fine particle dose and fraction (ANOVA p<0.05). Such observations may be attributed to the occupation of 'active' carrier sites by drug particles at low drug concentration, since the quantity of drug particles liberated from the carrier during aerosolisation remains constant at the lower dosing regimes.

Drug Delivery Systems↗

PubMed2003

Under pressure: predicting pressurized metered dose inhaler interactions using the atomic force microscope.

Drug particulate interactions in pressurized metered dose inhalers (pMDI) may lead to a decrease in aerosolization efficiency and subsequent efficacy in patient treatment. The interactions between salbutamol sulfate (commonly used in Ventolin pMDIs) and a series of pMDI canister materials were investigated using the atomic force microscope (AFM) colloid probe technique. Approximately 4000 individual force-distance curves were determined for a drug probe and three surfaces (10 x 10 mum areas) in situ, in a model propellant. The area under each force-distance curve was integrated to obtain separation energy values. Median separation energy values followed the rank order borosilicate glass > aluminum > PTFE, suggesting PTFE to be the most suitable canister coating.

Administration, Inhalation↗

PubMedDate not supplied

A novel apparatus for the determination of solubility in pressurized metered dose inhalers.

The accurate solubility of salbutamol sulfate, budesonide, and formoterol fumarate dihydrate in hydrofluoroalkane propellant 134a at 25 degrees C for 24 h, are reported. The authors describe a novel reusable in-line pressurized solubility apparatus containing an integral filter holder and a continuous decrimpable valve for the determination of drug/excipients solubility in pressurized metered dose inhalers. The solubility was determined by high-performance liquid chromatography. Solubility of salbutamol sulfate was determined as being below the detection limits while budesonide and formoterol fumarate dihydrate solubility were 23.136 +/- 2.951 microg x g(-1) and 0.776 +/- 1.023 microg x g(-1), respectively (n = 3). This novel solubility apparatus offers an improved ease of use and potential higher analytical throughput.

Administration, Inhalation↗