In this review, an extensive analysis of dry powder inhalers (DPIs) is offered, focusing on their characteristics, formulation, stability, and manufacturing. The advantages of pulmonary delivery were investigated, as well as the significance of the particle size in drug deposition. The preparation of DPI formulations was also comprehensively explored, including physico-chemical characterization of powders, powder processing techniques, and formulation considerations. In addition to manufacturing procedures, testing methods were also discussed, providing insights into the development and evaluation of DPI formulations. This review also explores the design basics and critical attributes specific to DPIs, highlighting the significance of their optimization to achieve an effective inhalation therapy. Additionally, the morphology and stability of 3 DPI capsules (Spiriva, Braltus, and Onbrez) were investigated, offering valuable insights into the properties of these formulations. Altogether, these findings contribute to a deeper understanding of DPIs and their development, performance, and optimization of inhalation dosage forms.
27 December 2020 in Pharmaceutical Development and Technology
Due to their light consistency and good spreadability, aqueous foams are considered as convenient and highly accepted drug carrier systems that are of great importance in the field of topical drug delivery. The production of a stable, easy to dose, preferably environmentally harmless foam formulation is challenging. Therefore, foam characterisation requires a complex approach: several tests are to be performed throughout the formulation. Our study primarily aims to investigate the quality attributes of propellant-free foam-forming additives. Throughout the research, we focused on acquiring knowledge about the properties of pharmaceutical excipients suitable for foam formulations and their effect on foam characteristics. Not only were the relative foam density, actuated foam weight and the foam collapse tendencies studied, but also the initial liquid properties. Along with surface tension determination, bubble-forming experiments were carried out. The bubble size and rate of formation, standardised by using a texture analyser, were followed by image analysis. Analysing the bubble-forming properties of dilute surfactant solutions allows assumptions on the properties of foam formed from the more concentrated solutions. The size and number of bubbles in the produced foams are related to the kinetics of single bubble formation. For comparison, commercially available medicated foams were studied. Graphical Abstract
Background/Objectives: This study investigates the impact of high humidity (25 °C, 75% relative humidity) on gelatin and hydroxypropyl methylcellulose (HPMC) capsules used in dry powder inhalers (DPIs), focusing on moisture dynamics, structural responses, and mechanical performance, with an emphasis on understanding how different capsule types respond to prolonged exposure to humid conditions. Methods: Capsules were exposed to controlled humidity conditions, and moisture uptake was measured via thermal analysis. Visual observations of silica bead color changes were performed to assess moisture absorption, while surface wettability was measured using the sessile drop method. Hardness testing, mechanical deformation, and puncture tests were performed to evaluate structural and mechanical changes. Positron annihilation lifetime spectroscopy (PALS) was used to analyze free volume expansion. Results: HPMC capsules exhibited rapid moisture uptake, attributed to their lower equilibrium moisture content and ability to rearrange dynamically, preventing brittleness. In contrast, gelatin capsules showed slower moisture absorption but reached higher equilibrium levels, resulting in plasticization and softening. Mechanical testing showed that HPMC capsules retained structural integrity with minimal deformation, while gelatin capsules became softer and exhibited reduced puncture resistance. Structural analysis revealed greater free volume expansion in HPMC capsules, consistent with their amorphous nature, compared with gelatin’s semi-crystalline matrix. Conclusions: HPMC capsules demonstrated superior humidity resilience, making them more suitable for protecting moisture-sensitive active pharmaceutical ingredients (APIs) in DPI formulations. These findings underline the importance of appropriate storage conditions, as outlined in the Summary of Product Characteristics, to ensure optimal capsule performance throughout patient use.
The inhalation therapy is one of the oldest drug delivery methods known. The significance of inhalation can be understood notably through its remarkable history. The goals of this review are to explore the pulmonary drug delivery, its significant relevance and various advantageous properties, particularly due to the physiology of the lungs. The drug delivery into the lungs can be provided by several inhalation instruments presently accessible on the market such as nebulizers, MDIs, and DPIs. Supplementary devices suchlike spacers for instance are also available in order to optimize the therapy results. The efficiency of these devices depends on several parameters of the formulation used, as well as its deposition in the lungs. Therefore, this review focuses on the meticulous testing performed on both the formulation and the device carrying it in the interest of insuring safety, quality, and efficacy of the final product. Ultimately, the pulmonary drug delivery represents a substantially advantageous alternative route of administration to obtain a systemic effect as well. This review aims to the better understanding of the development of pulmonary dosage forms and its complex process which requires extensive considerations and thorough optimization.
Bioconjugation is an emerging field in the food and pharmaceutical industry. Due to its biocompatibility and high ligand binding capacity, albumin is widely used in modern drug delivery systems. However, the protein is sensitive to environmental stresses; albumin conjugates, on the other hand, have improved functional properties. Biopolymers are gaining interest due to their biodegradability and safety, compared to synthetic polymers. In this study, albumin–biopolymer bioconjugates were prepared by nonenzymatic Maillard reaction at 60 °C and 80% relative humidity. This nonenzymatic conjugation takes place between reducing sugars and available amino groups of a protein in certain conditions. The optimal molar ratio and time for the conjugation were studied by several investigation methods, including circular dichroism and fluorescence spectroscopy, sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS–PAGE), and determination of available amino groups with ortho-phthaldialdehyde (OPA) assay. All of the measurements provided evidence for the covalent bonding of albumin and biopolymers, resulting in bioconjugates. Based on the results, a higher molar ratio and longer time are necessary to complete the reaction with the available amino groups. However, the optimal parameters are specific to each given biopolymer. The rheological behavior of the conjugates is characteristic of the initial biopolymer, which can be useful in drug development. Moreover, both the physical characteristics of albumin and the solubility-improving capacity were enhanced. Therefore, the potential use of albumin–biopolymer bioconjugates in the pharmaceutical industry could be considered.