Patient Acceptability and Preferences for Solid Oral Dosage Form Drug Product Attributes: A Scoping Review.

Background: 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.

Patients And Methods: A scoping review was conducted.

Titanium Dioxide (E171 Grade) and the Search For Replacement Opacifiers and Colorants: Supplier Readiness Survey, Case Studies and Regulatory Perspective.

Titanium dioxide (TiO2) is used primarily as an opacifier in solid dosage forms and is present in the majority of tablet and capsule dosage forms on the market. The IQ* TiO2 Working Group has previously shown that titanium dioxide has unique properties which are necessary for its function in these formulations and noted that, as the potential replacements lack the semi-conductor properties, high refractive index and whiteness of E171, it might be hard to replicate these properties with alternative materials. In this paper we detail the results of readiness surveys and practical assessments that have been conducted with alternative materials by IQ member companies.

Excipient Taxonomy for the 21st Century.

The performance of pharmaceutical dosage forms relies heavily on the characteristics of the excipients that are incorporated into the drug product during the manufacturing process. Therefore, it is imperative that formulators are able to accurately and completely specify the key chemical and physical properties of those excipients. Current approaches to describing excipients are outdated and inadequate for the needs of the 21 century and in this article we highlight the benefits of a more systematic and comprehensive approach to specifying and controlling excipient properties.

The Role of Titanium Dioxide (E171) and the Requirements for Replacement Materials in Oral Solid Dosage Forms: An IQ Consortium Working Group Review.

Titanium dioxide (in the form of E171) is a ubiquitous excipient in tablets and capsules for oral use. In the coating of a tablet or in the shell of a capsule the material disperses visible and UV light so that the contents are protected from the effects of light, and the patient or caregiver cannot see the contents within. It facilitates elegant methods of identification for oral solid dosage forms, thus aiding in the battle against counterfeit products.

Binary isobaric phase diagrams of stearyl alcohol-poloxamer 407 formulations in the molten and solid state.

Multiparticulate formulations allow for the design of specialized pharmaceutical dosage forms that cater to the needs of a wide range of patient demographics, such as pediatric and geriatric populations, by affording control over the release rate and facilitating the formulation of fixed-dose combination drugs. Melt spray-congealing (MSC) is a method for preparing multiparticulate dosage forms from a suspension or solid solution of active pharamaceutical ingredients (API) and a molten carrier matrix. Stearyl alcohol and poloxamer 407 mixtures are widely used as carrier matrices in MSC microsphere formulations.

The Wall Friction Properties of Pharmaceutical Powders, Blends, and Granulations.

Data from wall friction testing and physical property characterization of over 100 pharmaceutical powders, blends, and granulations have been analyzed. The analyses focused on data for stainless steel surfaces with the most common finishes for pharmaceutical powder processing equipment, either a 2B cold rolled mill finish or an electropolished 2B surface. Active pharmaceutical ingredients exhibited the highest friction against these surfaces, whereas active granulations exhibited the least friction.

Predicting the Crystallization Propensity of Drug-Like Molecules.

Predicting the crystallization propensity of drug-like molecules is one of the most significant challenges facing pharmaceutical scientists today. Despite the importance of being able to understand what structural features of a molecule (polarity, molecular size, etc.) and which experimental conditions (temperature, concentration, etc.

Quantification of Tribocharging of Pharmaceutical Powders in V-Blenders: Experiments, Multiscale Modeling, and Simulations.

Pharmaceutical powders are very prone to electrostatic charging by colliding and sliding contacts. In pharmaceutical formulation processes, particle charging is often a nuisance and can cause problems in the manufacture of products, such as affecting powder flow, fill, and dose uniformity. For a fundamental understanding of the powder triboelectrification, it is essential to study charge transfer under well-defined conditions.

A combined experimental and numerical approach to explore tribocharging of pharmaceutical excipients in a hopper chute assembly.

Electrostatic charging via contact electrification or tribocharging refers to the process of charge transfer between two solid surfaces when they are brought into contact with each other and separated. Charging of continuous particulate flows on solid surfaces is poorly understood and has often been empirical. This study aims toward understanding the tribocharging of pharmaceutical excipients using a simplified geometry of unidirectional flow in a hopper-chute assembly.

Surface acidity and solid-state compatibility of excipients with an acid-sensitive API: case study of atorvastatin calcium.

The objectives of this study were to measure the apparent surface acidity of common excipients and to correlate the acidity with the chemical stability of an acid-sensitive active pharmaceutical ingredient (API) in binary API-excipient powder mixtures. The acidity of 26 solid excipients was determined by two methods, (i) by measuring the pH of their suspensions or solutions and (ii) the pH equivalent (pHeq) measured via ionization of probe molecules deposited on the surface of the excipients. The chemical stability of an API, atorvastatin calcium (AC), in mixtures with the excipients was evaluated by monitoring the appearance of an acid-induced degradant, atorvastatin lactone, under accelerated storage conditions.

Ultrasonic approach for viscoelastic and microstructure characterization of granular pharmaceutical tablets.

The mechanical properties of a solid dosage, defined by its granular micro-structure and geometry, play a key role in its dissolution profile and performance. An ultrasonic method for extracting the viscoelastic material properties and granular structure of drug tablet compacts is introduced and its utility is demonstrated for tablet compacts made of microcrystalline cellulose (MCC), lactose monohydrate, and sodium starch glycolate as well as magnesium stearate as lubricant. The approach is based on the effect of viscoelasticity and internal micro-structures on the frequency-dependent attenuation of an ultrasonic wave propagating in a granular medium.

How do formulation and process parameters impact blend and unit dose uniformity? Further analysis of the product quality research institute blend uniformity working group industry survey.

Responses from the second Product Quality Research Institute (PQRI) Blend Uniformity Working Group (BUWG) survey of industry have been reanalyzed to identify potential links between formulation and processing variables and the measured uniformity of blends and unit dosage forms. As expected, the variability of the blend potency and tablet potency data increased with a decrease in the loading of the active pharmaceutical ingredient (API). There was also an inverse relationship between the nominal strength of the unit dose and the blend uniformity data.

Ultrasonic real-time in-die monitoring of the tablet compaction process-a proof of concept study.

The mechanical properties of a drug tablet can affect its performance (e.g., dissolution profile and its physical robustness.

Effect of particle size on energy dissipation in viscoelastic granular collisions.

We analyze the scaling properties of the Hertz-Kuwabara-Kono (HKK) model, which is commonly used in numerical simulations to describe the collision of macroscopic noncohesive viscoelastic spherical particles. Parameters describing the elastic and viscous properties of the material, its density, and the size of the colliding particles affect the restitution coefficient ɛ and collision time τ only via appropriate rescaling but do not change the shape of ɛ(v) and τ(v) curves, where v is the impact velocity. We have measured the restitution coefficient experimentally for relatively large (1 cm) particles of microcrystalline cellulose to deduce material parameters and then to predict collision properties for smaller microcrystalline cellulose (MCC) particles by assuming the scaling properties of the HKK model.

Acoustic assessment of mean grain size in pharmaceutical compacts.

An ultrasonic non-destructive technique for the microstructure length-scale characterization of solid dosage pharmaceutical tablets is presented. The technique is based on the relationship between the attenuation of longitudinal ultrasonic elastic waves and the size of micro-structural features in the tablet material. In the reported experiments, the ultrasonic attenuation in microcrystalline cellulose (MCC)-lactose monohydrate (LMH) blended pharmaceutical compacts is measured by means of two pitch-catch experiments.

Discrete element method (DEM) simulations of stratified sampling during solid dosage form manufacturing.

Discrete element model (DEM) simulations of the discharge of powders from hoppers under gravity were analyzed to provide estimates of dosage form content uniformity during the manufacture of solid dosage forms (tablets and capsules). For a system that exhibits moderate segregation the effects of sample size, number, and location within the batch were determined. The various sampling approaches were compared to current best-practices for sampling described in the Product Quality Research Institute (PQRI) Blend Uniformity Working Group (BUWG) guidelines.

The coefficient of restitution of some pharmaceutical tablets/compacts.

When tablets collide during manufacturing and handling operations they rebound with a force and velocity that is determined by the collision conditions and the properties of the materials. This collision-rebound behavior of solid bodies can be described using a parameter known as the "coefficient of restitution" (CoR). In this work, the CoR of a range of pharmaceutical tablets/compacts is measured using a simple "drop test", and the influences of material properties (elastic modulus, solid fraction, etc.

Correlating particle hardness with powder compaction performance.

Assessing particle mechanical properties of pharmaceutical materials quickly and with little material can be very important to early stages of pharmaceutical research. In this study, a wide range of pharmaceutical materials were studied using atomic force microscopy (AFM) nanoindentation. A significant amount of particle hardness and elastic modulus data were provided.