Pharmaceutical aerosols for the treatment and prevention of Tuberculosis

Abstract

Historically, pharmaceutical aerosols have been employed for the treatment of obstructive airway diseases, such as asthma and chronic obstructive pulmonary disease, but in the past decades their use has been expanded to treat lung infections associated with cystic fibrosis and other respiratory diseases. Tuberculosis (TB) is acquired after inhalation of aerosol droplets containing the bacilli from the cough of infected individuals. Even though TB affects other organs, the lungs are the primary site of infection, which makes the pulmonary route an ideal alternative route to administer vaccines or drug treatments. Optimization of formulations and delivery systems for anti-TB vaccines and drugs, as well as the proper selection of the animal model to evaluate those is of paramount importance if novel vaccines or drug treatments are to be successful. Pharmaceutical aerosols for patient use are generated from metered dose inhalers, nebulizers, and dry powder inhalers (DPIs). In addition to the advantages of providing more efficient delivery of the drug, low cost, and portability, pharmaceutical dry powder aerosols are more stable than inhalable liquid dosage forms and do not require refrigeration. Methods to manufacture dry powders in respirable sizes include micronization, spray drying, and other proprietary technologies. Inhalable dry powders are characterized in terms of their drug content, particle size, and dispersibility to ensure deposition in the appropriate lung region and effective aerosolization from the device. These methods will be illustrated as they were applied for the manufacture and characterization of powders containing anti-tubercular agents and vaccines for pulmonary administration. The influence of formulation, selection of animal model, method of aerosol generation, and administration on the efficacy demonstrated in a given study will be illustrated by the evaluation of pharmaceutical aerosols of anti-TB drugs and vaccines in guinea pigs by our group.

Nano-Vesicles of Salbutamol Sulphate in Metered Dose Inhalers: Formulation, Characterization and in Vitro Evaluation

“…In this light, release can be changed by varying system surface area and wettability; determined by size and uniformity. Meanwhile, loading percentage directly affects the drug concentration gradient and release rate [30]. Further kinetic studies were carried out and the release pattern was non fickian with n = 0.6929 for N (table 2).…”

Pulmonary drug delivery systems for tuberculosis treatment

“…They are also packed to protect them from light and humidity, which enhances their stability (Hanif and GarciaContreras, 2012). Dry powders for inhalation may consist of: (i) micronized drugs, (ii) mixtures of micronized drugs and micronized carriers, (iii) drug-loaded micro or nanoparticles blended with micronized carriers, or (iv) dry particles composed of drug and excipients (Frijlink and De Boer, 2004;Hanif and Garcia-Contreras, 2012). In the last case the drug-loaded particles plays the role of the Table 2 Structures, minimum inhibitory concentration and mechanism of action of anti-TB drugs.…”

Sharpening nature's tools for efficient tuberculosis control: A review of the potential role and development of host-directed therapies and strategies for targeted respiratory delivery

“…Animal studies generally begin with small rodents such as mice, rats and guinea pigs for a number of reasons: small quantities of formulation can be administered therefore scale-up of manufacturing may be kept to a minimum, lower cost than larger animals and a considerable amount of data is required from in vivo studies which must be statistically significant and so smaller animals generally allow greater power for studies [297]. The disadvantages of using rodents relate mainly to differences in physical, physiological, genetics, and hence immune response, as eluded to in discussion regarding the suitability of murine versus human macrophages for in vitro efficacy testing (4.2.1) making extrapolation of results difficult at times [298].…”