Spray-dried particles as pulmonary delivery system of anti-tubercular drugs: design, optimization, in vitro and in vivo evaluation.
Currently, one-third of the world's population is infected with tuberculosis (TB) mainly spread by inhalation of the tubercle bacilli, Mycobacterium tuberculosis. Patient non-compliance is the major reason for failure of anti-tubercular drugs (ATDs) chemotherapy due to multidrug administration for longer duration of time period. The main aim of current research study was to develop and characterize inhalable spray-dried particles for pulmonary delivery of ATDs, i.e., rifampicin (RIF) and isoniazid (INH). ATDs-loaded alginate particles were prepared by ionotropic gelation technique followed by spray drying and characterized on the basis of various evaluation parameters. Results showed that the optimized spray-dried particles were found to be spherical in shape with excellent flow properties. The drug release showed the biphasic pattern of release, i.e., initial burst (30-40% up to 4 h) followed by a sustained release pattern (90% up to 60 h). Optimized formulations exhibited lower cytotoxicity and excellent lung uptake up to 8 h. Optimized formulation also showed higher rate and extent of drug uptake by lungs due to preferential phagocytosis be macrophage. In future, alginate particles could be a promising carrier for targeted delivery of ATDs to alveolar macrophages for efficient management of TB.
a Department of Pharmaceutics , ISF College of Pharmacy, Nanomedicine Research Centre , Moga , Punjab , India , affiliated from Punjab Technical University, Kapurthala, Punjab, India.
Tarun
T
Garg
a Department of Pharmaceutics , ISF College of Pharmacy, Nanomedicine Research Centre , Moga , Punjab , India , affiliated from Punjab Technical University, Kapurthala, Punjab, India.
Amit K
AK
Goyal
a Department of Pharmaceutics , ISF College of Pharmacy, Nanomedicine Research Centre , Moga , Punjab , India , affiliated from Punjab Technical University, Kapurthala, Punjab, India.
Goutam
G
Rath
a Department of Pharmaceutics , ISF College of Pharmacy, Nanomedicine Research Centre , Moga , Punjab , India , affiliated from Punjab Technical University, Kapurthala, Punjab, India.
R S R
RS
Murthy
D000280:Administration, Inhalation; D000464:Alginates / Q000737:chemistry; D000818:Animals; D000995:Antitubercular Agents / Q000008:administration & dosage* / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003692:Delayed-Action Preparations / Q000008:administration & dosage; D004339:Drug Compounding / Q000379:methods; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D007538:Isoniazid / Q000008:administration & dosage / Q000737:chemistry; D008168:Lung / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D010316:Particle Size; D012293:Rifampin / Q000008:administration & dosage / Q000737:chemistry; D014376:Tuberculosis / Q000188:drug therapy*
D000464:Alginates; D000995:Antitubercular Agents; D003692:Delayed-Action Preparations; D006603:Hexuronic Acids; D020723:Glucuronic Acid; D007538:Isoniazid; D012293:Rifampin
Alginate; in vitro and in vivo studies; pulmonary drug delivery; spray-dried particle; tuberculosis