Selection of Silica Type and Amount for Flowability Enhancements via Dry Coating: Contact Mechanics Based Predictive Approach.

Purpose: To investigate the effect of dry coating the amount and type of silica on powder flowability enhancement using a comprehensive set of 19 pharmaceutical powders having different sizes, surface roughness, morphology, and aspect ratios, as well as assess flow predictability via Bond number estimated using a mechanistic multi-asperity particle contact model.

Method: Particle size, shape, density, surface energy and area, SEM-based morphology, and FFC were assessed for all powders. Hydrophobic (R972P) or hydrophilic (A200) nano-silica were dry coated for each powder at 25%, 50%, and 100% surface area coverage (SAC).

Hydrogel-Embedded Poly(Lactic--Glycolic Acid) Microspheres for the Delivery of hMSC-Derived Exosomes to Promote Bioactive Annulus Fibrosus Repair.

Objective: Intervertebral disk degeneration is a prevalent postoperative complication after discectomy, underscoring the need to develop preventative and bioactive treatment strategies that decelerate degeneration and seal annulus fibrosus (AF) defects. Human mesenchymal stem cell-derived exosomes (MSC-Exos) hold promise for cell-free bioactive repair; however, their ability to promote AF repair is poorly understood. The objective of this study was to evaluate the ability of MSC-Exos to promote endogenous AF repair processes and integrate MSC-Exos within a biomaterial delivery system.

Fine grade engineered microcrystalline cellulose excipients for direct compaction: Assessing suitability of different dry coating processes.

Recent work showed that contrary to conventional wisdom, fine surface engineered excipients outperform their larger counterparts in blends of highly loaded blends of cohesive drug powders in terms of their packing, flowability and tablet tensile strength. Here, two continuous devices, fluid-energy mill (FEM) and conical mill (Comil), are compared with LabRAM, a batch device used in previous work, for nano-silica dry coating of microcrystalline cellulose (MCC) excipients, 20 and 30 μm. Coated MCCs from all three devices had higher bulk densities and flow function coefficients (FFCs) compared with Avicel PH-102.

Surface engineered excipients: III. Facilitating direct compaction tableting of binary blends containing fine cohesive poorly-compactable APIs.

Direct compaction tableting, a desired manufacturing option, is infeasible for blends containing fine cohesive poorly-compactable APIs at higher drug loadings. In this study, the feasibility of using fine, dry coated excipients is investigated instead of dry coating of the APIs, as was done previously. Avicel PH-105 (20.

Effect of Particle Size and Polymer Loading on Dissolution Behavior of Amorphous Griseofulvin Powder.

The effect of particle size on the dissolution behavior of the particles of amorphous solid dispersions (ASDs) of griseofulvin (GF), with 0%-50% Kollidon VA 64 as a crystallization inhibitor is investigated. Both the final dissolved GF concentration and the dissolution rate of GF ASDs were found to be inversely proportional to the particle size. The solution concentrations for the smallest (45-75 μm) size group with different polymer loadings were significantly higher than those for the largest (250-355 μm) group regardless of the initial GF amount.

Surface engineered excipients: II. Simultaneous milling and dry coating for preparation of fine-grade microcrystalline cellulose with enhanced properties.

A solventless process for simultaneously milling and dry coating microcrystalline cellulose (MCC) was investigated for producing fine excipients in five different sizes (∼20, 25, 30, 35, 40 µm) having high bulk density (BD), good flow function coefficient (FFC), and excellent compaction. Avicel PH-102, used as the starting material, was milled and coated with two grades of silicas, hydrophobic and hydrophilic (R972P and A200), using a fluid energy mill (FEM). Through judicious selection of the FEM feed rate, feeding pressure, and grinding pressure, five desired milled sizes were produced.

Impact of Superdisintegrants and Film Thickness on Disintegration Time of Strip Films Loaded With Poorly Water-Soluble Drug Microparticles.

Although strip films are a promising platform for delivery of poorly water-soluble drug particles via slurry casting, the effect of critical material attributes, for example, superdisintegrants (SDIs) on critical quality attributes, including film disintegration time (DT), remains underexplored. A 2-level factorial design is considered to examine the impact of the SDI type (sodium starch glycolate and croscarmellose sodium), their amount, and film thickness. SDIs were used with hydroxypropyl methylcellulose (E15LV) and glycerin solutions along with viscosity matching.

Improved properties of fine active pharmaceutical ingredient powder blends and tablets at high drug loading via dry particle coating.

It has been shown that dry coating cohesive active pharmaceutical ingredients (APIs) with nano-silica can improve packing and flow of their blends, facilitating high speed direct compression tableting. This paper examines the broader scope and generality of previous work by examining three fine APIs; micronized Acetaminophen (mAPAP), coarse Acetaminophen (cAPAP) and micronized Ibuprofen (mIBU), and considers dry coating with both hydrophobic or hydrophilic nano-silica to examine the effect not only on packing density and flow of their blends, but also dissolution and tensile strength of their tablets. The impact of the excipient size on blend and tablet properties are also investigated, indicating blend flow is most improved when matching API particle size with excipient particle size.

Surface engineered excipients: I. improved functional properties of fine grade microcrystalline cellulose.

Excipients with good flowability, bulk density as well as compaction properties are desired for use in tableting since they play important roles in formulation development and processing, including, handling, mixing, feeding and compaction. The objective of this paper is to examine the feasibility of using dry coating based surface modification of microcrystalline cellulose, Avicel PH-105, to produce an engineered fine grade (<30 μm) excipient that has all three desired properties. Using a material sparing high-intensity vibrational mixer, Avciel PH-105 is dry coated with 1 wt% Aerosil 200, selected due to its relatively higher dispersive surface energy and lower particle size amongst other silica choices.

Improving blend content uniformity via dry particle coating of micronized drug powders.

Content uniformity of low dose blends with fine active pharmaceutical ingredients (API) is adversely impacted due to API agglomeration caused by high powder cohesion. Dry coating using high-intensity vibratory mixing is employed to reduce API cohesion and granular Bond number as well as agglomeration as predicted by contact models, hence improve blend content uniformity (CU). Micronized acetaminophen (mAPAP) (~10μm), a model API, was dry coated with nano-silica R972P (20nm), and mixed with Avicel 102.