Evaluation of highly branched cyclic dextrin in inhalable particles of combined antibiotics for the pulmonary delivery of anti-tuberculosis drugs

Kadota, Kazunori; Senda, Arisa; Tagishi, Hideaki; Ayorinde, John Oluwasogo; Tozuka, Yuichi

doi:10.1016/j.ijpharm.2016.11.060

Cited by 37 publications

(10 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To maximize the therapeutic efficacy of drugs currently available for TB treatment, the search for new modified release systems is of utmost importance. ,− These systems can increase the solubility, permeability, and stability of the drug, making them more bioavailable. In addition, there is the possibility of a prolonged release of the drug, maintaining its plasma concentration at constant therapeutic levels throughout the day.…”

Section: Introdutionmentioning

confidence: 99%

Obtaining and Applying Nanohybrid Palygorskite-Rifampicin in the pH-Responsive Release of the Tuberculostatic Drug

et al. 2020

View full text Add to dashboard Cite

Despite having good efficacy in the treatment and prevention of tuberculosis, the administration of rifampicin (RIF) can cause serious side effects, resulting from the prolonged use of this substance. Thus, it is necessary to seek new systems for administering tuberculostatic drugs, to avoid unwanted adverse effects, increase their bioavailability and, consequently, improve their therapeutic efficacy. The present work describes the achievement of a pH-responsive system for RIF, using palygorskite, a fibrous clay mineral, as a nanocarrier. To evaluate the influence of some operational variables on the drug adsorption process, a 2 4 factorial experimental design was used. The experiment using a maximum concentration (0.125 mg/mL), lower mass of PAL (300 mg), and lower pH (pH 2) was more efficient compared to other experiments, resulting in a higher dose of the incorporated drug, equivalent to 33.62 mg/g. To elucidate the mechanism of interaction between the materials, the hybrid obtained was characterized by different characterization techniques (Fourier transform infrared spectroscopy, X-ray diffraction, thermogravimetry/derived thermogravimetry, zeta potential, scanning electron microscopy, and dispersive energy spectroscopy). In addition, kinetic models and adsorption isotherms were applied to the experimental data. Through in vitro release studies, it was possible to verify the effectiveness of the pH-dependent system obtained. The adjustment of experimental release data to the theoretical model of Higuchi indicated that the release of rifampicin occurs in a prolonged way from the palygorskite.

show abstract

Section: Introdutionmentioning

confidence: 99%

Obtaining and Applying Nanohybrid Palygorskite-Rifampicin in the pH-Responsive Release of the Tuberculostatic Drug

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Pulmonary drug delivery is an important area of research with potential to impact the treatment of lung specific diseases, such as asthma, chronic obstructive pulmonary disease (COPD) or respiratory tract infections (Chow et al, 2007;Kadota et al, 2017;Weers and Miller, 2015). Delivery to the lungs may also be employed to effect bioabsorption of small drugs or therapeutic peptides in order to obtain a systemic effect (Amaro et al, 2015a;Amaro et al, 2015b;Ógáin et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

A Design of Experiment (DoE) approach to optimise spray drying process conditions for the production of trehalose/leucine formulations with application in pulmonary delivery

Focaroli

Mah

Hastedt

et al. 2019

International Journal of Pharmaceutics

View full text Add to dashboard Cite

The present study evaluates the effect of L-leucine concentration and operating parameters of a laboratory spray dryer on characteristics of trehalose dry powders, with the goal of optimizing production of these powders for inhaled drug delivery. Trehalose/L-leucine mixtures were spray dried from aqueous solution using a laboratory spray dryer. A factorial design of experiment (DoE) was undertaken and process parameters adjusted were: inlet temperature, gas flow rate, feed solution flow rate (pump setting), aspiration setting and L-leucine concentration. Resulting powders were characterised in terms of particle size, yield, residual moisture content, and glass transition temperature. Particle size was mainly influenced by gas flow rate, whereas product yield and residual moisture content were found to be primarily affected by inlet temperature and spray solution feed rate respectively. Interactions between a number of different process parameters were elucidated, as were relationships between different responses. The leucine mass ratio influenced the physical stability of powders against environmental humidity, and a high leucine concentration (30% w/w) protected amorphous trehalose from moisture induced crystallization. High weight ratio of leucine in the formulation, however, negatively impacted the aerosol performance. Thus, in terms of L-leucine inclusion in a formulation designed for pulmonary delivery, a balance needs to be found between physical stability and deposition characteristics.

show abstract

“…As a result, higher local concentrations are attained, which may even exterminate bacteria that are considered resistant [4]. With the lower systemic exposure resulting from a more targeted approach, systemic side effects (such as oto- or hepatotoxicity) are reduced [2,3,4,5,6,7].…”

Section: Introductionmentioning

confidence: 99%

Characterization and Formulation of Isoniazid for High-Dose Dry Powder Inhalation

et al. 2019

View full text Add to dashboard Cite

Tuberculosis is a major health problem and remains one of the main causes of mortality. In recent years, there has been an increased interest in the pulmonary delivery of antibiotics to treat tuberculosis. Isoniazid is one of these antibiotics. In this study, we aimed to characterize isoniazid and formulate it into a dry powder for pulmonary administration with little or no excipient, and for use in the disposable Twincer® inhaler. Isoniazid was jet milled and spray dried with and without the excipient l-leucine. Physiochemical characterization showed that isoniazid has a low Tg of −3.99 ± 0.18 °C and starts to sublimate around 80 °C. Milling isoniazid with and without excipients did not result in a suitable formulation, as it resulted in a low and highly variable fine particle fraction. Spray drying pure isoniazid resulted in particles too large for pulmonary administration. The addition of 5% l-leucine resulted in a fraction <5 µm = 89.61% ± 1.77% from spray drying, which dispersed well from the Twincer®. However, storage stability was poor at higher relative humidity, which likely results from dissolution-crystallization. Therefore, follow up research is needed to further optimize this spray dried formulation.

show abstract

Evaluation of highly branched cyclic dextrin in inhalable particles of combined antibiotics for the pulmonary delivery of anti-tuberculosis drugs

Cited by 37 publications

References 41 publications

Obtaining and Applying Nanohybrid Palygorskite-Rifampicin in the pH-Responsive Release of the Tuberculostatic Drug

Obtaining and Applying Nanohybrid Palygorskite-Rifampicin in the pH-Responsive Release of the Tuberculostatic Drug

A Design of Experiment (DoE) approach to optimise spray drying process conditions for the production of trehalose/leucine formulations with application in pulmonary delivery

Characterization and Formulation of Isoniazid for High-Dose Dry Powder Inhalation

Contact Info

Product

Resources

About