Development of Isoniazid Loaded Nanotechnology-Based Dry Powder Pulmonary Formulations for Treatment of Tuberculosis

• Main Author: Mukhtar, Mahwash
• Format: Dissertation
• Language: English
• Published: ProQuest Dissertations & Theses 01-01-2022
• Subjects: Drug delivery systems; Epidemiology; FDA approval; Marketing; Pharmaceutical sciences; Pharmaceuticals; Pharmacology; Product development; Tuberculosis
• ISBN: 9798381089189

Tuberculosis (TB) is the leading cause of death of over 1.5 million people annually across the globe and the second leading infectious disease after COVID-19 pandemic, according to the statistics by the world health organization (WHO). At present, multidrug-resistant TB remains a public health crisis in undeveloped countries due to compromised socio-economic conditions (WHO, 2021). Lungs are the primary site for Mycobacterium tuberculosis (M.Tb) infection which is a facultative intracellular bacterium. M.Tb gains access to the lungs by inhalation of infected air droplets from the cough of an infected person. Following inhalation, M.Tb interacts with the mucous secreting goblet cells and some of the infected particles bypass the mucociliary system and, ultimately enter into the alveoli. During this pathogenesis, M.Tb is taken up by the alveolar macrophages (AM) using the ligand lipoarabinomannan. This ligand of the bacterium interacts with the mannose surface receptors of the AM to gain access to the macrophages where it resides and multiples in the phagocytes [1]. M.Tb interacts with the T-lymphocytes to differentiate macrophages into granulomas characterized by the infiltration of inflammatory mononuclear cells. Later, the T-lymphocytes (effector cells) produce cytokines to facilitate the activation of previously infected macrophages to kill the M.Tb residing inside. Hence, T-cell response and activation are essential to the immune regulation in TB [2].TB is curable but the ineffective management, high costs of therapy, and patient incompliance contribute to the alarming rise in cases in this modern era. Hence, a cost-effective and patientfriendly drug delivery approach is essential to the treatment of TB. Development of the rational patient-friendly pharmaceutical dosage form is the time consuming and extensive work. However, the use of robust regulatory guidelines can minimize the development time of the dosage form without compromising quality by following the European Medicines Agency (EMA) and U.S. Food and Drug Administration (FDA) protocols at various steps. The quality by design (QbD) method is one such systematic approach and effective application that takes into consideration every aspect of product quality attributes during the early stage of dosage development whereas the design of experiment (DoE) facilitates the optimization of a pharmaceutical formulation [3].