Influence of blister package design on usability among older adults.

BACKGROUND: Blisters packs are commonly used as packaging for oral drug products. Utilization problems among older adults with pharmaceutical packaging are well known from investigations of multi-unit dose containers, but there is a lack of studies focusing on blister packaging. This study was performed to identify design parameters that should be considered when developing blister packaging for drug products intended to be used by older adults. OBJECTIVES: To investigate the relationship between blister pack design and utilization problems among older adults. SETTING: Community-based study including 141 volunteers (age 80+) living at home and in assisted-living facilities. METHOD: In random order 5 blister packs of uniform shape but with different opening characteristics (variation of the force required to open the blisters and different mechanisms of opening) were tested by each participant. MAIN OUTCOME MEASURE: Opening was evaluated (difficulty, pain perception and overall assessment) by questioning of the participants. Additionally, data were collected as to whether participants managed to take out 4 tablets within 4 min test duration and whether they gave up opening. Reasons for utilization problems were examined by subgroup analysis, frequently made observations, and technological characterization of blisters. Results Blisters with thicker push-through foils were assessed as being inferior. Anyhow, most of participants (>84 %) were capable of opening each type of push-through blister within 4 min. By contrast, many of the participants were unable to open peel (30 %) and child-resistant peel-off push-through blisters (44 %) or gave up trying before the end of the test. In addition to medical conditions, vision and age of participants correlated with utilization problems. CONCLUSION: Blister pack design, including opening force and opening mechanism, can have significant impact on the usability of blister packs by older adults. The study identified several parameters that should be considered with respect to older adults when developing blister packaging for drug products.

Influences of heat seal lacquer thickness on the quality of blister packages.

A sealability of aluminium lidding foils against formable polymer materials of blister packages is usually achieved by a coating of aluminium with certain grammages of heat seal lacquers. To investigate influences of their thickness on quality of blister packages, lidding foils with different grammages of two lacquer types were manufactured. Sealing experiments (variation of temperature, pressure and sealing time) were performed. Sealed seam strengths were determined with mechanical tensile tests, tightness of cold form blisters were analysed by means of helium leakage tests. Time-dependent moisture uptake of stored blisters was monitored with micro-gas chromatography. By means of a simple calculation model the permeability coefficients of the heat seal lacquers were determined. Lidding foils with higher lacquer grammages showed significantly greater sealed seam strengths. Helium leakage tests showed only slight effects of heat seal lacquer grammage on tightness of blisters. But cold form blisters with lidding foils of higher lacquer grammages showed a significantly greater moisture uptake. Since the heat seal lacquers and the rigid polyvinyl chloride of the formable aluminium compound foils had similar permeability coefficients, the contribution of the lacquers to the total permeability of the investigated cold form blisters was only slightly.

Comparison of quantitative analysis techniques for the determination of heat seal lacquer layers on aluminum blister foils.

For decades a gravimetric method has been common standard for the determination of heat seal lacquers on aluminum blister foils. With the availability of appropriate techniques such as interferometric, infrared reflection absorption spectroscopic (IRRAS), beta backscatter, impedance spectroscopic and eddy current techniques respectively, more efficient determinations can be foreseen which are subject of the present communication. The different methods were compared to each other regarding parameters required for validation of analytical procedures according to the ICH guidelines Q2 (R1) such as linearity, precision, accuracy, robustness and quantitation limits. The interferometric, IRRAS and beta backscatter techniques were well suitable for the measurements. Using these techniques novel procedures applicable for routine quality control of pharmaceutical packaging materials are suggested.

Effect of interactive ternary mixtures on dispersion characteristics of ipratropium bromide in dry powder inhaler formulations.

The purpose of this investigation was to evaluate the effect of mixing order and the influence of adding fines on in vitro performance of ipratropium bromide (ITB) dry powder inhaler formulations. Coarse lactose (CL) in varying mass ratio with or without addition of micronized lactose (ML) and ITB in different mixing sequences was used to formulate ternary mixtures. A binary mixture composed of CL and ITP served as control. The in vitro deposition of ITB from these formulations was measured using an Andersen cascade impactor (aerosolization at 39 L/min) employing a HandiHaler as the delivery device. It was observed that mixing order has a significant effect (P < .05) on in vitro deposition of ITB. Formulations with preblending of CL and ITB produced similar deposition profiles as the control, regardless of the added ML. In contrast, formulations without preblending resulted in significantly higher fine particle dose (FPD) as compared with the control. In addition, an increased quantity of ML generally resulted in an increase in drug deposition. The results show that the effect of ML on dispersion of ITB is highly dependent upon the mixing order. The evaluation of atomic force measurement (AFM) to forecast drug detachment and predict the aerodynamic characteristics resulted in similar attraction forces for the different pairs lactose/lactose (42.66 +/- 25.01 nN) and lactose/ITB (46.77 +/- 17.04 nN).

High-performance liquid chromatography of lactose with evaporative light scattering detection, applied to determine fine particle dose of carrier in dry powder inhalation products.

A method for quantification of the fine particle dose of lactose is described, using a hydrophilic interaction chromatography (HILIC) method and evaporative light scattering detection. The HILIC method used an aminopropyl column and a mobile phase consisting of acetonitril/water (80/20, v/v) for isocratic elution. Sensitive chromatography was obtained using a low concentration of water in the extraction solvent. The detection limit (RSD<10%) at an injection volume of 10 microL is 10 microg/mL. Linearity was obtained in the range of 10-80 microg/mL (R(2)>0.99). A relative standard deviation (RSD) of 0.5% (N=6) demonstrated good precision of the optimized method.

Conditioning following powder micronization: influence on particle growth of salbutamol sulfate.

Micronization is a high-energy process that induces changes in the crystallinity of materials. As a result, the crystalline structures on the particles' surface are being destroyed and amorphous areas are formed. After micronization of salbutamol sulfate to be used in dry powder inhalers, only small amounts of amorphous material are produced. Nevertheless, even these small amounts can have important effects on the physical stability of the powder. The amorphous state is thermodynamically unstable and tends to convert to the stable, crystalline state. The recrystallization process of disordered regions on the particles' surface leads to particle growth of milled particles. In this case, bridges of solid material are being formed between the individual particles, which leads to particle growth. This is an undesirable process, because particles for pulmonary administration are designed to range between 1 and 10 microm in diameter to exert respirative effect. In the present investigation, salbutamol sulfate is micronized by an air jet mill, and the generated products are exposed to different conditions. Thereafter, the best possible conditioning parameters and storage conditions for the micronized salbutamol sulfate are worked out and rated. The aim of this treatise is to demonstrate the importance of conditioning following micronization.

Influence of mechanical activation on the physical stability of salbutamol sulphate.

In order to obtain the optimal particle size distribution for pharmaceutical powders in dry powder inhalers the particles have to be micronised. In most cases the process of micronisation is connected with a high input of energy which induces disorder and defects on the surface of the drug particles and as a result changes in the crystallinity. Consequently, changes in the physical stability of the powders may occur. To investigate changes on the physical stability of the powder, different analytical methods are used in the present investigation: laser diffraction, Differential Scanning Calorimetry (DSC), isothermal microcalorimetry and DVS-method.Air-jet-milling is one of the most frequently used techniques in the pharmaceutical industry, in order to obtain particles of respirable size. In the treatise described here the influence of the critical parameters of the process, i.e. feed pressure, grind pressure and feed rate is assessed for salbutamol sulphate. The grind pressure is of utmost importance with respect to particle size distribution and the physical powder stability. For salbutamol sulphate, ground with a MC Jetmill 50, a grind pressure of 6 bar has been found optimal. Pressures below 6 bar are not sufficient to produce the required reduction in particle size. The feed pressure and rate have negligible influence on the powder quality. Furthermore, the micronisation process is optimised to achieve respirable particles while minimising the amorphous content. A correlation between mechanical activation and the amount of the amorphous regions is showed clearly.Air-jet-milling has been compared to ball milling in this investigation. In pilot tests ball milling was not suitable to achieve the needed particle size distribution, however, it generates a specific quantity of amorphous material. With the help of specific amorphous regions in the powder, the sensitivity of the used methods for salbutamol sulphate can be examined.