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Crystal morphology plays an important role in drug processing and delivery, which may be controlled during crystallisation. In this study, ibuprofen particles with different size and morphology were produced by controlled crystallisation in order to evaluate their impact on particle size reduction. Results suggest that the micronisation behaviour of ibuprofen was markedly influenced by the morphology and size of starting materials. It was possible to reduce the size of ibuprofen particles to sizes less than 5 µm during dry milling, which is markedly below the reported brittle–ductile transition size. Results also indicate that the particle size reduction mechanism is influenced by the size and morphology of the starting ibuprofen crystals. Dissolution behaviour of ibuprofen was shown to be influenced by the solid surface chemistry of micronised drug particles. The molecular modelling study provided deeper understanding of the experimental findings observed in this study.

Particle size reduction by mechanical means is an important unit operation in the pharmaceutical industry, used to improve flow, solubility, and in amorphization of drugs. It is usually achieved by the fracturing of particles under the action of applied energy. Despite being pervasive in the pharmaceutical field, it is one of the least understood processes owing to the complexity of material and process variables involved during milling. To comprehend the process, efforts should be focused on techniques that measure the particle size as well as the control the process. With the ongoing initiative of US FDA to encourage design in quality, the review is focused on some process analytical tools to characterize particle size distribution as well as process modeling tools to simulate particle size reduction. Additionally, an overview of some fundamental aspects related to milling is provided. To this end, the review is limited, mainly concentrating on some of experimental and modeling approaches used to quantify and understand the physics behind the process of dry milling.

The aim of this study is the introduction of a novel apparatus that is capable of continuously measuring the particle size reduction of disintegrating tablets and analysis of the obtained results. The apparatus is constructed such that no particles pass directly through the pumping system. Thereby, the overall energy input into the particle suspension is reduced, and continuous measurement is possible without rapid destruction of the generated particles. The detected particle sizes at the beginning and at the end of the measurement differ greatly, depending on the applied disintegrant. The median particle sizes at the end of the measurement vary between 621.5 and 178.0 μm for different disintegrants. It is demonstrated that the particle size reduction follows an exponential function and that the fit parameters can be used to describe the disintegration behavior. A strong correlation between the median particle size of crospovidone disintegrants and generated particle size of the tablets is observed. This could be due to a more homogeneous distribution of the disintegrant particles in the tablets. Similar trends are observed for sodium starch glycolate and croscarmellose sodium. The new apparatus provides an innovative method to describe disintegrant effectiveness and efficiency. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:3657–3665, 2014

Particle size reduction can be used for enhancing the dissolution of poorly water-soluble drugs in order to enhance bioavailability. In nanosuspensions, the particle size of the drug is reduced to nanometer size. Nanosuspensions after downstream processing into drug products have successfully shown its impact on formulation design, the augmentation of product life cycle, patent life, and therapeutic efficacy. Formulation considerations for the nanosuspension formulation, its processing into a solid form, and aspects of material characterization are discussed. Technology assessments and feasibility of upstream processes for nanoparticle creation, and subsequently transformation into a drug product via the downstream processes have been reviewed. This paper aims to bridge formulation and process considerations along with patent reviews and may provide further insight into understanding the science and the white space. An analysis of current patent outlook and future trends is described to fully understand the limitations and opportunities in intellectual property generation.

This manuscript describes the preparation, characterization, and pharmacokinetic studies for fluticasone and budesonide nanosuspensions in pulmonary delivery. A wet-milling method with glass beads was evaluated for formulation preparation. Based on the milling time and glass bead size studies, a 24-h wet-milling process using multisized glass beads was found to be the most efficient method to achieve consistent particle size reduction. It was used to prepare nanosuspensions for characterization and pharmacokinetic studies to evaluate formulation performance. For characterization studies, particle size distribution, crystalline form, potency and homogeneity, and stability during storage were evaluated. Nanosuspensions for both compounds exhibited good physical/chemical properties for pulmonary delivery. The pharmacokinetic studies after the intratracheal administration of nanosuspensions showed deep lung deposition and fast lung absorption, with solubility playing an important role in lung retention and duration of action. Overall, these studies have demonstrated that nanosuspensions can be used for pulmonary drug delivery in preclinical animal studies.

One factor that must be considered during drug development process is that various types of pharmaceutical manufacturing can alter the physical characteristics of the drug entity. These effects become particularly important during scale-up of processing operations, because new and unanticipated results can become manifest in systems of insufficient characterization. Any transformed drug substance or altered dosage form could exhibit an altered solubility or dissolution rate that might produce an undesirable bioavailability profile. Some of the more interesting mechanical manipulations that have the potential to yield problems include particle size reduction and compression, and such investigations are the focus of this minireview.

This report deals with basic studies concerned with the use of sieving as an accurate means of classifying granular pharmaceutical solids. Attention was focused on the effects of sieve shaker speed, initial load and particle size distribution of the granulation on the rate of particle size reduction and the cumulative per cent of material passing a sieve. The size and concentration of the smaller-than-mesh particles were shown to exert a profound influence on the equilibrium time of a sieve. Using a nest of sieves, an equilibrium time technique was developed to obtain the particle size distribution and permit calculation of various statistical parameters dependent on the observance of the log-normal law. An equilibrium time procedure such as developed here permits the quantitative classification of granular pharmaceutical solids by sieving, with a better assurance that separatio: has been achieved with the minimum of attrition.