Medicines for delivering therapeutic agents to the lung as dry powders primarily consist of a carrier and a micronised active pharmaceutical ingredient (API). The performance of an inhaled ...formulation will depend on a number of factors amongst which the particle size distribution (PSD) plays a key role. It is suggested that increasing the number of fine particles in the carrier can improve the aerosolisation of the API. In addition the effect of PSD upon a bulk powder is also broadly understood in terms of powder flow. Other aspects of functionality that different size fractions of the carrier affect are not clearly understood; for example, it is not yet clearly known how different size fractions contribute to the different functionalities of the carrier. It is the purpose of this investigation to examine the effects of different lactose size fractions on fine particle dose, formulation stability and the ability to process and fill the material in the preferred device. In order to understand the true impact of the size fractions of lactose on the performance of dry powder inhaled (DPI) products, a statistically designed study has been conducted. The study comprised various DPI blend formulations prepared using lactose monohydrate carrier systems consisting of mixtures of four size fractions. Interactive mixtures were prepared containing 1% (w/w) salbutamol sulphate. The experimental design enabled the evaluation of the effect of lactose size fractions on processing and performance attributes of the formulation. Furthermore, the results of the study demonstrate that an experimental design approach can be used successfully to support dry powder formulation development.
There is no consistent framework for patient-centric drug product design, despite the common understanding that drug product acceptability and preferences influence adherence and, therefore, drug ...product effectiveness. The aim of this review was to assess current understanding of patient acceptability and preferences for solid oral dosage form (SODF) drug product attributes, and the potential impact of these attributes on patient behaviors and outcomes.BackgroundThere is no consistent framework for patient-centric drug product design, despite the common understanding that drug product acceptability and preferences influence adherence and, therefore, drug product effectiveness. The aim of this review was to assess current understanding of patient acceptability and preferences for solid oral dosage form (SODF) drug product attributes, and the potential impact of these attributes on patient behaviors and outcomes.A scoping review was conducted. Embase, Ovid MEDLINE®, and PubMed® were searched for full-text articles published between January 2013 and May 2023. Following screening and assessment against predefined inclusion criteria, data were analyzed thematically.Patients and MethodsA scoping review was conducted. Embase, Ovid MEDLINE®, and PubMed® were searched for full-text articles published between January 2013 and May 2023. Following screening and assessment against predefined inclusion criteria, data were analyzed thematically.Nineteen studies were included. Four overarching domains of drug product attributes were identified and summarized in a framework: appearance, swallowability, palatability, and handling. Each domain was informed by specific drug product attributes: texture, form, size, shape, color, marking, taste, mouthfeel, and smell. The most frequently studied domains were swallowability and appearance, while the most studied attributes were size, shape, and texture. Smell, marking, and mouthfeel were the least studied attributes. Texture intersected all domains, while form, shape, and size intersected appearance, swallowability, and handling. Swallowability and size appeared to be the key domain and attribute, respectively, to consider when designing drug products. Few studies explored the impact of drug product attributes on behaviors and outcomes.ResultsNineteen studies were included. Four overarching domains of drug product attributes were identified and summarized in a framework: appearance, swallowability, palatability, and handling. Each domain was informed by specific drug product attributes: texture, form, size, shape, color, marking, taste, mouthfeel, and smell. The most frequently studied domains were swallowability and appearance, while the most studied attributes were size, shape, and texture. Smell, marking, and mouthfeel were the least studied attributes. Texture intersected all domains, while form, shape, and size intersected appearance, swallowability, and handling. Swallowability and size appeared to be the key domain and attribute, respectively, to consider when designing drug products. Few studies explored the impact of drug product attributes on behaviors and outcomes.While existing studies of drug product attributes have focused on appearance and swallowability, this review highlighted the importance of two less well-understood domains-palatability and handling-in understanding patients' acceptability and preferences for SODF drug products. The framework provides a tool to facilitate patient-centric design of drug products, organizing and categorizing physical drug product attributes into four overarching domains (appearance, swallowability, palatability, and handling), encouraging researchers to comprehensively assess the impact of drug product attributes on patient acceptability, preferences, and outcomes.ConclusionWhile existing studies of drug product attributes have focused on appearance and swallowability, this review highlighted the importance of two less well-understood domains-palatability and handling-in understanding patients' acceptability and preferences for SODF drug products. The framework provides a tool to facilitate patient-centric design of drug products, organizing and categorizing physical drug product attributes into four overarching domains (appearance, swallowability, palatability, and handling), encouraging researchers to comprehensively assess the impact of drug product attributes on patient acceptability, preferences, and outcomes.
The purpose is to investigate the use of thermal nanoprobes in thermomechanical and heated tip pulsed force modes as novel means of discriminating between amorphous and crystalline material on a ...sub-micron scale.
Indometacin powder was compressed and partially converted into amorphous material. Thermal nanoprobes were used to perform localised thermomechanical analysis (L-TMA) and heated tip pulsed force mode imaging as a function of temperature.
L-TMA with submicron lateral spatial resolution and sub-100 nm depth penetration was achieved, allowing us to thermomechanically discriminate between amorphous and crystalline material at a nanoscale for the first time. The amorphous and crystalline regions were imaged as a function of temperature using heated tip pulsed force AFM and a resolution of circa 50 nm was achieved. We are also able to observe tip-induced recrystallisation of the amorphous material.
The study demonstrates that we are able to discriminate and characterise amorphous and crystalline regions at a submicron scale of scrutiny. We have demonstrated the utility of two methods, L-TMA and heated tip pulsed force mode AFM, that allow us to respectively characterise and image adjacent amorphous and crystalline regions at a nanoscale.
The study has demonstrated that thermal nanoprobes represent a novel method of characterising and imaging partially amorphous materials.
The study describes the development of a novel approach to surface analysis whereby thermal probes are used to perform scanning probe microscopy pull-off force measurements as a function of tip ...rather than sample temperature. The initial impetus for the investigation was the study of a poorly understood phenomenon associated with microthermal analysis (MTA) whereby the thermal probe is pulled into the surface of a sample following temperature-induced softening. Localized thermomechanical analysis experiments were performed on a range of pharmaceutical materials using TA Instruments 2990 Microthermal Analyzer equipped with a TM Microscopes Explorer atomic force microscope. The system was then interfaced with a second instrument to allow simultaneous probe temperature control and pull-off force measurement. It was found that the pull-in effect is due to the adhesion of the probe to the material at elevated (softening) temperatures. However, it was also noted that for paracetamol tablets the pull-off force increased at temperatures well below the softening associated with melting. This behavior was ascribed to surface polymorphic changes caused by the compression process. The temperature-controlled pull-off force method therefore represents a novel and potentially widely applicable means of detecting surface changes that are not easily observed using isothermal pull-off force measurements or indeed standard MTA studies.
The aim of this study was to develop a novel approach to the spatial characterization of multicomponent samples, based on the emergent technique of microthermal analysis. More specifically, we ...present an assessment of the use of scanning thermal microscopy as a means of component mapping via thermal conductivity; we include a new statistical approach to data handling, which allows reduction of topographic effects. We also introduce a novel three-dimensional mapping technique based on localized thermomechanical analysis. Tablets of paracetamol and hyproxypropyl methylcellulose (HPMC) and 50:50 mixes of the two were prepared and the materials characterized in scanning and localized modes using a TA Instruments 2990 microthermal analyzer with a Thermomicroscopes Explorer AFM head and Wollaston wire thermal probe. L-TMA studies of the pure components indicated markedly differing thermal responses, with the paracetamol showing a sharp melting accompanied by a probe pull-in effect, while HPMC showed only thermal expansion over the temperature range studied. Thermal conductivity and topographic images indicated that two-dimensional differentiation between the components was possible in scanning mode. A means of delineating the relative contribution of the topographic and conductivity effects was developed based on a regression analysis of the thermal conductivity measurements on a set of terms representing the local surface curvature. The results of three-dimensional imaging using a grid of L-TMA measurements is presented. This technique utilized the distinct thermal responses of the two components to allow the probe to melt through the paracetamol down to the underlying HPMC. The advantages and limitations of this novel imaging method are discussed in the context of pharmaceutical and broader uses of the approach.
