The effect of sinusoidal vibration on the uniformity of packing of powder beds

Sinusoidal vibration, at a number of defined sets of conditions, has been applied to packings of certain particle size fractions of lactose. The distribution of local porosity within these vibrated packings was determined using a gamma-ray attenuation technique, and could be compared with porosity data for samples not subjected to vibration. It was found that the application of vibration in a vertical mode markedly increased the uniformity of packing; horizontal vibration was less effective in this respect. The relationship between local porosity and position with a packing, observed in most non-vibrated samples, was generally absent from vibrated packings.     

The influence of carrier roughness on adhesion, content uniformity and the in vitro deposition of terbutaline sulphate from dry powder inhalers

The aim of this study was to establish a correlation between carrier characteristics and the dispersibility of drug from the blend. The influence of the roughness of a commonly used carrier material, lactose monohydrate, on the adhesion, dose uniformity, and aerodynamic properties of a model drug, terbutaline sulphate was investigated. Evaluation of adhesion was carried out with a mechanical sieve and an Alpine air-jet sieve. For the characterisation of lactose roughness, we used image analysis software. Aerodynamic evaluation of fine particle dose and emitted dose was obtained using a twin stage impinger. The study with the mechanical sieve demonstrated that at least 60% of drug adheres to lactose. The Alpine air-jet sieve assays showed there was a correlation between drug separation from a carrier by sieving and that obtained from longer in vitro deposition studies. Adhesion, blend homogeneity and stability are related to the surface roughness of the lactose used as carrier. There is a linear relationship between the parameters "fine particle fraction" and "roughness". A compromise between homogeneity and drug liberation must be found: a certain roughness is necessary to allow for drug adhesion and blend homogeneity, but if too high it will prevent drug liberation after inhalation.     

The influence of initial packing on the compression of powders

The influence of the initial packing density on the compression properties of lactose and sodium chloride has been studied. Differences in initial packing density are eliminated for both materials at relatively low pressures. The results have been analysed by the equations of Kawakita (1956), Heckel (1961), and Cooper & Eaton (1962). The constants derived from the Cooper & Eaton equation are dependent on the choice of low pressure data. The Kawakita constants are influenced by the initial packing of the powder. The Heckel treatment uses data at pressures above the point where the initial packing exerts an influence. Hence the constants are independent of the initial packing. If comparisons are to be made between processing treatments or mixtures which change the initial packing of the powder, the Heckel equation would appear to offer the most valid approach.     

The influence of initial packing on the compression of powders

The influence of the initial packing density on the compression properties of lactose and sodium chloride has been studied. Differences in initial packing density are eliminated for both materials at relatively low pressures. The results have been analysed by the equations of Kawakita (1956), Heckel (1961), and Cooper & Eaton (1962). The constants derived from the Cooper & Eaton equation are dependent on the choice of low pressure data. The Kawakita constants are influenced by the initial packing of the powder. The Heckel treatment uses data at pressures above the point where the initial packing exerts an influence. Hence the constants are independent of the initial packing. If comparisons are to be made between processing treatments or mixtures which change the initial packing of the powder, the Heckel equation would appear to offer the most valid approach.     

影响利福平胶囊装量差异的因素

利福平胶囊是一种高效“超广谱”的抗生素药物。装量差异是该药最基本的检测指标,其影响因素主要包括利福平原粉自身的物理性状及胶囊剂的分装工艺。本文主要针对上述两方面加以阐述,并提出采用湿法制粒工艺来改善利福平原粉的物理性状,使制粒后的原粉满足利福平胶囊的生产工艺,有效地控制利福平胶囊的半量稳定性。     

Determination of porosity variations in powder beds

A gamma-ray attenuation technique for detecting local porosity variations in packings of pharmaceutical powders has been developed and assessed. It proved necessary to employ an empirical expression describing the attenuation coefficient of the model material, lactose, as a function of porosity. The precision of measurement of local porosity can be pre-selected due to the statistical basis of the method, and local porosity measurements with 95% confidence intervals of +/- 0.005 can readily be carried out. A method of producing grey-scale images of porosity distributions has been employed to enable the degree of inhomogeneity of a powder bed to be seen.     

The influence of spray properties on intranasal deposition.

While numerous devices, formulations, and spray characteristics have been shown to influence nasal deposition efficiency, few studies have attempted to identify which of these interacting factors plays the greatest role in nasal spray deposition. The deposition patterns of solutions with a wide range of surface tensions and viscosities were measured using an MRI-derived nasal cavity replica. The resulting spray plumes had angles between 29 degrees and 80 degrees and contained droplet sizes (D(v50)) from 37-157 microm. Each formulation contained rhodamine 590 as a fluorescent marker for detection. Administration angles of 30 degrees , 40 degrees , or 50 degrees above horizontal were tested to investigate the role of user technique on nasal deposition. The amount of spray deposited within specific regions of the nasal cavity was determined by disassembling the replica and measuring the amount of rhodamine retained in each section. Most of the spray droplets were deposited onto the anterior region of the model, but sprays with small plume angles were capable of reaching the turbinate region with deposition efficiencies approaching 90%. Minimal dependence on droplet size, viscosity, or device was observed. Changes in inspiratory flow rate (0-60 L/min) had no significant effect on turbinate deposition efficiency. Both plume angle and administration angle were found to be important factors in determining deposition efficiency. For administration angles of 40 degrees or 50 degrees , maximal turbinate deposition efficiency (30-50%) occurred with plume angles of 55-65 degrees , whereas a 30 degrees administration angle gave an approximately 75% deposition efficiency for similar plume angles. Deposition efficiencies of approximately 90% could be achieved with plume angles <30 degrees using 30 degrees administration angles. Both the plume angle and administration angle are critical factors in determining deposition efficiency, while many other spray parameters, including particle size, have relatively minor influences on deposition within the nasal cavity.     

Studies on the influence of uniformity of particle size of powder, tapping and sample replacement for diffusion reflectance quantitative NIR spectrometric analysis

The extent of deviation factors and the influence of pre-processing of spectra for a quantitative application of reflectance NIR measurement against powder sample were examined. Lactose monohydrate (NGLM), a medical additive was used for this study. Ground lactose monohydrate (GLM) and NGLM were measured by NIR reflectance spectroscopy. In the wave number range from 12000 cm(-1) to 4000 cm(-1), the ratios of absorbance values (a.v.) between the wave numbers of GLM and NGLM were almost the same and no influence of intensity of absorbance through the measurement range was observed concerning heterogeneity of particle size. Absorbance values of NGLM were decreased with increasing number of tapping without a bit difference of the change of a.v. The several statistical parameters of a.v. from both samples were estimated. The relative standard deviation (RSD) and 95% confidence intervals (CIs) of a.v. on successive measurements at a fixed position in GLM and NGLM vials were almost the same. However, the RSD and 95% confidence of absorbance value of NGLM were larger than these GLM, i.e., RSD: 0.66% for NGLM, 0.42% for GLM. The 95% of CI of NGLM was ten times larger than that of GLM in five replacement positions. The two kinds of baseline corrections, the SNV and MSC processing were examined to evaluate the extent of influence against a.v. The 95% CI calculated from a.v. by the SNV pre-processing showed a wider range compared with that from no pre-processing and MSC pre-processing. These results suggest that the statistical confidence of a.v. would also change by pre-processing. It is important to consider the statistical confidence of a.v. for precise quantitative application of the reflectance NIR spectroscopy.     

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.     

Ab initio structure determination of rofecoxib from powder diffraction data using molecular packing analysis method and direct space method

Crystal structures of a COX-II inhibitor, rofecoxib (Vioxx) were solved ab initio from X-ray powder diffraction pattern using both molecular packing analysis and direct space methods. The X-ray powder pattern was indexed into a tetragonal cell. Packing energies were generated and analyzed in eight most frequently found tetragonal space groups. The two space groups with the lowest total energy, P4(1)2(1)2 and P4(3)2(1)2, were used for direct space method with a Monte-Carlo/Simulated Annealing searching algorithm. Structural solutions obtained from direct space method were evaluated using molecular packing energy analysis. The structures solved ab initio from this work were compared to the single crystal structure deposited in the Cambridge Structural Database.     

Relationship between particle packing and the physical stability of powder mixes

The segregation tendency of powder mixes containing sugar-based direct compression tableting excipients with comparable particle size distributions and flow properties was studied under different vibration conditions. It was found that Tabfine and fine-particle pyridoxine hydrochloride mixes were virtually segregation-free, whereas segregation occurred in each of the other powder mixes containing Fast-flo, Dipac and Nu-tab. The segregation tendency of a specific powder mix following vibration was considered to be influenced by the packing of excipient particles in the powder bed. In general, the more densely packed the particles under given vibration conditions, the lower the segregation tendency. This was considered to be due to the tightly packed powder bed restricting individual particle movement and thereby reducing particle or ordered unit rearrangement.     

The influence of thioacetamide upon plutonium deposition in the rat

It has been shown that the distribution of plutonium in rats can be influenced by oral administration of thioacetamide (300 mg/kg). Rats injected intraperitoneally with plutonium citrate retained 71.5 and 23.6% of the recovered activity in the carcass and liver, respectively, whereas rats which had been treated with thioacetamide 24 hr previously contained 35.8 and 59.5% of the plutonium in the carcass and liver, respectively. It is possible that the hepatic phospholipids, the concentrations of which are increased by thioacetamide, act as ionophores in the concentration of cations in the liver.     

The influence of orifice height on flow rate of powder excipients

The influence of the orifice height of a cylindrical, flat-bottomed hopper on the mass flow rate of the free-flowable size fractions of sodium chloride and boric acid was investigated. It was observed that a zone of sudden acceleration of the mass flow under gravity occurred when a critical orifice height had been achieved. Based on the results, an orifice diameter equal to 12 mm with a height of between 8-16 mm is recommended for the faster flow of sodium chloride while an orifice diameter equal to 8 mm with a height of less than 8mm is appropriate for the slower flow of boric acid. In summary, the orifice height should be taken into consideration as an important parameter of a cylindrical test hopper in order to obtain a reproducible and comparable mass flow as the single-point characteristic of powder flowability.     

Coating uniformity: influence of atomizing air pressure

The objective of this study was to investigate the influence of atomizing air pressure on the coating uniformity and the quality of the film coat. As parameters describing the coating uniformity, the mass variance of the film coated tablets and the variance of the film thickness within a tablet were used. For the examination of the properties of the film coat, the cumulative frequency of the tablet mass, the spray loss, the relative frequency of the film thickness, the minimum amount of polymer required for an enteric coating, and the swelling number were taken into consideration. For this study a Walther Pilot spray gun WA 50 with a liquid orifice diameter of 0.5 mm and a flat jet air cap was used. The experiments were carried out in a Bohle BLC 5 drum coater using four different atomizing air pressures between 0.5 and 2.0 bar. All other parameters were kept constant during the coating process. It could be shown that atomizing air pressure is an important factor influencing the quality and uniformity of a film coat. An increase in the atomizing air pressure will produce smooth tablets with a small mass variance. Due to a greater spray loss, the required minimum amount of polymer for an enteric coating is higher at an atomizing air pressure of 2.0 bar.     

In vitro evaluation of dry powder inhalers II: influence of carrier particle size and concentration on in vitro deposition

Dry powders and their delivery devices are an alternative to pressurized metered-dose inhalers (pMDI) for the administration of aerosols to the lungs. Generally dry powder aerosols are formulated by mixing a cohesive micronized drug with larger carrier particles resulting in an interactive powder mixture. Redispersion of the drug from agglomerates or the carrier surface during inhalation is a critical factor which greatly influences the fine particle fraction (particles<6.4 μm) to be achieved. Two devices, the single-unit-dose Spinhaler™ (Fisons) and the multiple-unit-dose Easyhaler™ (Orion Pharma) were used to investigate the influence of dry powder formulation on the deposition of interactive mixtures. Following the scheme of a 3²-factorial design budesonide was mixed with lactose-α-monohydrate varying the lactose sieve fractions and the drug to carrier proportion. The in vitro deposition of these mixtures was determined using a Twin Stage Impinger (Apparatus A, BP 93) and compared to control experiments performed with unsieved drug carrier. Deposition was found to be highly dependent on the dry powder formulation. Fine particle fractions from 10 up to 50% were observed. The Easyhaler™ shows little differences compared to the Spinhaler™ device.