Physical and chemical stability of drug nanoparticles

Top-Down Production of Drug Nanocrystals - Nanosuspension Stabilization, Miniaturization and Transformation Into Solid Products

Nanocrystals: Industrially feasible multifunctional formulation technology for poorly soluble actives

Drug molecules transformed into nanoparticles or endowed with nanostructures with or without the aid of carrier materials are referred to as "nanomedicines" and can overcome some inherent drawbacks of free drugs, such as poor water solubility, high drug dosage, and short drug half-life in vivo. However, most of the existing nanomedicines possess the drawback of low drug-loading (generally less than 10%) associated with more carrier materials. For intravenous administration, the extensive use of carrier materials might cause systemic toxicity and impose an extra burden of degradation, metabolism, and excretion of the materials for patients. Therefore, on the premise of guaranteeing therapeutic effect and function, reducing or avoiding the use of carrier materials is a promising alternative approach to solve these problems. Recently, high drug-loading nanomedicines, which have a drug-loading content higher than 10%, are attracting increasing interest. According to the fabrication strategies of nanomedicines, high drug-loading nanomedicines are divided into four main classes: nanomedicines with inert porous material as carrier, nanomedicines with drug as part of carrier, carrier-free nanomedicines, and nanomedicines following niche and complex strategies. To date, most of the existing high drug-loading nanomedicines belong to the first class, and few research studies have focused on other classes. In this review, we investigate the research status of high drug-loading nanomedicines and discuss the features of their fabrication strategies and optimum proposal in detail. We also point out deficiencies and developing direction of high drug-loading nanomedicines. We envision that high drug-loading nanomedicines will occupy an important position in the field of drug-delivery systems, and hope that novel perspectives will be proposed for the development of high drug-loading nanomedicines.

/pdf/high-drug-loading-nanomedicines-progress-current-status-and-1jd09wxqju.pdf

High drug-loading nanomedicines: progress, current status, and prospects

Objectives Wet milling is a common technique to produce drug nanocrystals. Stability of the nanocrystals is a critical question, and different kinds of stabilizers, e.g. polymers, celluloses, surfactants and lipids, have been tested for various drugs. Still, the question about how to select the best stabilizer to a certain drug material and also to a selected process is open.

Key findings  Many different factors, such as surface energy, hydrophobicity, solubility, viscosity and functional groups, affect the stability of the formed nanosuspensions. Affinity of the stabilizer to the particle surfaces seems to be the most important parameter. This affinity is partly related to the surface energy and hydrophobicity of the surfaces and stabilizers.

Summary  In this review the most important factors affecting nanocrystal formulation and efficacy of stabilizers are presented. In order to widen understanding of the milling process, the most important variables related to milling techniques and particle fracturing processes during the milling are briefly presented.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.2042-7158.2010.01022.x

Pharmaceutical nanocrystals by nanomilling: critical process parameters, particle fracturing and stabilization methods

The poorly soluble drug buparvaquone is proposed as an alternative treatment of Pneumocystis carinii pneumonia (PCP) lung infections. Physically stable nanosuspensions were formulated in order to deliver the drug at the site of infection using nebulization. The aerosolization characteristics of two buparvaquone nanosuspensions were determined with commercial jet and ultrasonic nebulizer devices. Aerosol droplet size distribution was determined with laser diffractometry (LD). Nebulization of the nanosuspensions and dispersion media surfactant solutions produced aerosol droplets diameters in the range from 3 to 5 microm for Respi-jet Kendall, Pari Turbo Boy system and Multisonic nebulizers and particles around 9-10 microm with Omron U1. Fractions of the nanosuspensions from the nebulizer reservoir and of aerosol produced were collected to investigate changes in the size of the drug nanocrystals influenced by the nebulization technology. Comparisons were performed measuring the drug nanocrystals with photon correlation spectroscopy (PCS) and LD of the samples. Drug particle aggregates were detected in the fractions of aerosol collected from jet nebulizers. Nebulizer technology (jet vs. ultrasonic) showed influence on the stability of the drug particle size distribution of buparvaquone nanocrystals during the nebulization time evaluated.

Hartwig Steckel

Papers

Characterization of nebulized buparvaquone nanosuspensions—effect of nebulization technology