Abstract
Tuberculosis (TB) is a contagious airborne disease caused by Mycobacterium tuberculosis, which primarily affects human lungs. The progression of drug-susceptible TB to drug-resistant strains, MDR-TB and XDR-TB, has become worldwide challenge in eliminating TB. The limitations of conventional TB treatment including frequent dosing and prolonged treatment, which results in patient’s noncompliance to the treatment because of treatment-related adverse effects. The non-invasive pulmonary drug administration provides the advantages of targeted-site delivery and avoids first-pass metabolism, which reduced the dose requirement and systemic adverse effects of the therapeutics. With the modification of the drugs with advanced carriers, the formulations may possess sustained released property, which helps in reducing the dosing frequency and enhanced patients’ compliances. The dry powder inhaler formulation is easy to handle and storage as it is relatively stable compared to liquids and suspension. This review mainly highlights the aerosolization properties of dry powder inhalable formulations with different anti-TB agents to understand and estimate the deposition manner of the drug in the lungs. Moreover, the safety profile of the novel dry powder inhaler formulations has been discussed. The results of the studies demonstrated that dry powder inhaler formulation has the potential in enhancing treatment efficacy.
Highlights
Tuberculosis (TB) is one of the major health concerns in the world, with at least 10 million people being infected each year [1]
This study showed that co-spray dried of PZA with 20% l-leucine in 10% of ethanol provided the best aerosolization performance among other formulations which provided a fine particles fraction (FPF) of 33.0 ± 4.1% and mass median aerodynamic diameter (MMAD) of 2.83 ± 0.04 μm
In the dynamic vapor sorption analysis, the results demonstrated that a lower mass change was observed in the formulation with higher lactide proportion compared to the formulation with lower lactide proportion, all the formulations were proven stable after exposure to humidity
Summary
Tuberculosis (TB) is one of the major health concerns in the world, with at least 10 million people being infected each year [1]. In the case of MDR-TB, the two most potent first-line anti-TB drugs, isoniazid (INH), and rifampicin (RIF) are reported ineffective in treating TB as the TB bacteria are resistant to those drugs. XDR-TB is a more severe form of drug-resistant TB caused by ineffective management of MDR-TB [3,4]. XDR-TB is a form of MDR-TB with additional resistance to any fluoroquinolone and at least one of the three injectable second-line anti-TB drugs (amikacin, kanamycin, or capreomycin). The efflux pump in M. tuberculosis can pump the antibiotics out of the bacterial cells which leads to drug resistance (Figure 1) [8,9]. The treatment for drug-resistant TB requires a longer period to complete and is manageable by second-line anti-TB drugs such as fluoroquinolones, kanamycin, linezolid, bedaquiline, cycloserine and pretomanid. MMeecchhaanniissmmss ooff bbaacctteerriiaall aannttiibbiioottiicc rreessiissttaannccee iinncclluuddee aalltteerraattiioonn iinn tthhee ddrruugg--ttaarrggeetteedd ggeenneess;; ddeeccrreeaasseedd ppeerrmmeeaabbiilliittyy ooff tthhee TTBB bbaacctteerriiaa cceellllwwaallllwwhihcihchinihnihbiitbsittshetheenteryntoryf aonftibaniottiibciso;tdicesg;rdadegatriaodnaotifoanntoibf iaontitcisbiboytiecns zbyymeantizcyamctaiotinc; alocstiso/anl;teloressd/ainltethreeddirnutgheendtrryugpoenrtt;reyxpporerts;seioxnproefsesfflionuxofpeufmflupxs ponumthpescoenll tmheemceblrlamnee.mbrane
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