PMID- 26406162
OWN - NLM
STAT- MEDLINE
DCOM- 20170201
LR  - 20170201
IS  - 1941-2703 (Electronic)
IS  - 1941-2711 (Linking)
VI  - 29
IP  - 2
DP  - 2016 Apr
TI  - Development and Evaluation of Chitosan Microparticles Based Dry Powder Inhalation 
      Formulations of Rifampicin and Rifabutin.
PG  - 179-95
LID - 10.1089/jamp.2014.1187 [doi]
AB  - BACKGROUND: The lung is the primary entry site and target for Mycobacterium 
      tuberculosis; more than 80% of the cases reported worldwide are of pulmonary 
      tuberculosis. Hence, direct delivery of anti-tubercular drugs to the lung would 
      be beneficial in reducing both, the dose required, as well as the duration of 
      therapy for pulmonary tuberculosis. In the present study, microsphere-based dry 
      powder inhalation systems of the anti-tubercular drugs, rifampicin and rifabutin, 
      were developed and evaluated, with a view to achieve localized and targeted 
      delivery of these drugs to the lung. METHODS: The drug-loaded chitosan 
      microparticles were prepared by an ionic gelation method, followed by 
      spray-drying to obtain respirable particles. The microparticles were evaluated 
      for particle size and drug release. The drug-loaded microparticles were then 
      adsorbed onto an inhalable lactose carrier and characterized for in vitro lung 
      deposition on an Andersen Cascade Impactor (ACI) followed by in vitro uptake 
      study in U937 human macrophage cell lines. In vivo toxicity of the developed 
      formulations was evaluated using Sprague Dawley rats. RESULTS: Both rifampicin 
      and rifabutin-loaded microparticles had MMAD close to 5 mum and FPF values of 
      21.46% and 29.97%, respectively. In vitro release study in simulated lung fluid 
      pH 7.4 showed sustained release for 12 hours for rifampicin microparticles and up 
      to 96 hours for rifabutin microparticles, the release being dependent on both 
      swelling of the polymer and solubility of the drugs in the dissolution medium. In 
      vitro uptake studies in U937 human macrophage cell line suggested that 
      microparticles were internalized within the macrophages. In vivo acute toxicity 
      study of the microparticles in Sprague Dawley rats revealed no significant 
      evidence for local adverse effects. CONCLUSION: Thus, spray-dried microparticles 
      of the anti-tubercular drugs, rifampicin and rifabutin, could prove to be an 
      improved, targeted, and efficient system for treatment of tuberculosis.
FAU - Pai, Rohan V
AU  - Pai RV
AD  - 1 Department of Pharmaceutics, Bombay College of Pharmacy , Kalina, Santacruz 
      (E), Mumbai, India .
FAU - Jain, Rajesh R
AU  - Jain RR
AD  - 1 Department of Pharmaceutics, Bombay College of Pharmacy , Kalina, Santacruz 
      (E), Mumbai, India .
FAU - Bannalikar, Anilkumar S
AU  - Bannalikar AS
AD  - 2 Department of Microbiology, Bombay Veterinary College , Parel, Mumbai, India .
FAU - Menon, Mala D
AU  - Menon MD
AD  - 1 Department of Pharmaceutics, Bombay College of Pharmacy , Kalina, Santacruz 
      (E), Mumbai, India .
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150925
PL  - United States
TA  - J Aerosol Med Pulm Drug Deliv
JT  - Journal of aerosol medicine and pulmonary drug delivery
JID - 101475057
RN  - 0 (Aerosols)
RN  - 0 (Antibiotics, Antitubercular)
RN  - 0 (Delayed-Action Preparations)
RN  - 0 (Drug Carriers)
RN  - 0 (Powders)
RN  - 1W306TDA6S (Rifabutin)
RN  - 9012-76-4 (Chitosan)
RN  - J2B2A4N98G (Lactose)
RN  - VJT6J7R4TR (Rifampin)
MH  - Administration, Inhalation
MH  - Aerosols
MH  - Animals
MH  - Antibiotics, Antitubercular/*administration & 
      dosage/chemistry/metabolism/toxicity
MH  - Chitosan/*chemistry/toxicity
MH  - Delayed-Action Preparations
MH  - *Drug Carriers
MH  - Drug Compounding
MH  - Drug Stability
MH  - *Dry Powder Inhalers
MH  - Female
MH  - Humans
MH  - Kinetics
MH  - Lactose/chemistry
MH  - Lung/*metabolism
MH  - Macrophages/metabolism
MH  - Particle Size
MH  - Powders
MH  - Rats, Sprague-Dawley
MH  - Rifabutin/*administration & dosage/chemistry/metabolism/toxicity
MH  - Rifampin/*administration & dosage/chemistry/metabolism/toxicity
MH  - Solubility
MH  - Surface Properties
MH  - U937 Cells
OTO - NOTNLM
OT  - Andersen Cascade Impactor (ACI)
OT  - chitosan microparticles
OT  - dry powder inhaler
OT  - macrophage uptake
EDAT- 2015/09/26 06:00
MHDA- 2017/02/02 06:00
CRDT- 2015/09/26 06:00
PHST- 2015/09/26 06:00 [entrez]
PHST- 2015/09/26 06:00 [pubmed]
PHST- 2017/02/02 06:00 [medline]
AID - 10.1089/jamp.2014.1187 [doi]
PST - ppublish
SO  - J Aerosol Med Pulm Drug Deliv. 2016 Apr;29(2):179-95. doi: 
      10.1089/jamp.2014.1187. Epub 2015 Sep 25.