This document summarizes research on developing dry powder formulations for treating tuberculosis (TB) via inhalation. It discusses how pulmonary delivery of anti-TB drugs can provide local high drug concentrations with lower systemic doses compared to oral or parenteral routes. Several techniques for producing dry powder anti-TB formulations are described, including spray drying and particle engineering methods. The document also outlines challenges in developing stable dry powder formulations and consistent drug delivery devices for treating TB patients via inhalation.

1. Aug 17, 2017
(Mentor Institute)
DRY POWDER FORMULATION FOR
TREATING TUBERCULOSIS
PRESENTED BY
SACHIN SANAP
M.S. (PHARM.)- PHARMACEUTICS
SECOND SEMESTER
ID NO- 410/16
RAEBARELIRAEBARELI

2.  CONTENTSCONTENTS
INTRODUCTION
PULMONARY ROUTES
INHALATION DELIVERY DEVICES FOR PULMONARY DELIVERY
DRUGS STUDIED FOR PULMONARY DELIVERY USING DPI
TECHNIQUES USED FOR PRODUCTION OF ANTI-TB FORMULATIONS
FORMULATION APPROACHES FOR DPI FOR TUBERCULOSIS
CHALLENGES FOR DEVELOPING DPI FOR TB PATIENTS
CONCLUSION
REFERENCES
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3.  INTRODUCTIONINTRODUCTION
Tuberculosis (TB) is an infectious disease caused by
Mycobacterium tuberculosis (MTB).
 World Health Organization (WHO), one third of the world
population (around 2 billion) is estimated to be infected with
MTB while 2 million people die of TB each year and 8
million develop active TB.
The severity has been complicated due to Acquired
Immuno Deficiency Syndrome (AIDS) and the emergence
of multi-drug resistant TB (MDR-TB)
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4.  PULMONARY DELIVERY
 Treat conditions like asthma and COPD (chronic
obstructive pulmonary disease), providing local and
systemic action.
Advantages:
 Avoid first pass metabolism.
 Employed for local and systemic effect.
 Greater bioavailability and less systemic toxicity.
 Targeted delivery is possible.
 Provides quick onset of action.
 Non-invasive delivery of drug.
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5. Besides these advantages pulmonary drug delivery also has
some of limitations like
There may be local side effect due to deposition of drug
in oropharynx
Limited drug absorption due to mucosal barrier.
Improper use of pulmonary drug device.
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6.  Inhalation delivery devices for pulmonary deliveryInhalation delivery devices for pulmonary delivery
Fig.1. A nebulizer may achieve atomization of droplets by a stream of compressed air, or through
piezoelectric sonication, or by mechanical means such as a vibrating mesh or spring-loaded
nozzle.[2]
Fig.2. A pMDI uses a dose-metering valve to deliver medicament suspended in a propellant spray.
[2]
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7. Fig.3. DPI delivers a more gentle stream of inhalant through indrawn breath.[2]
A dry-powder inhaler (DPI) is a device that delivers
medication to the lungs in the form of a dry powder.
DPIs are commonly used to treat respiratory diseases
such as asthma, bronchitis, emphysema and COPD
although DPIs (such as inhalable insulin Afrezza) have
also been used in the treatment of diabetes mellitus.
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8.  Drugs Studied for Pulmonary Delivery Using DPIDrugs Studied for Pulmonary Delivery Using DPI
Table 1. Dry powder inhalers of single anti-TB drug formulations..
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Drug Method Formulation Key outcome
Rifampicin Spray drying
Rifampicin-lactose
composite
Rifampicin and lactose
retained crystalline structure.
Rifampicin
Recrystallisation and
spray drying Crystalline powder
Improved aerosolisation
properties, fine particle
fraction (FPF) 68%
Rifapentine
Crystallisation and
spray drying
Crystalline and
amorphous powder
High FPF of 83% and 69% for
crystalline and amorphous
powder, respectively.
...
Isoniazid
Supercritical fluid-
spray drying
Microparticles enriched
with leucine
Particle size within inhalable
range.

9. Aug 17, 2017 8
Drug Formulation Key outcome
Rifampicin+
Isoniazid PLA microparticles
Intra-alveolar drug concentration was higher
than drug alone formulation
Rifampicin +
Isoniazid +
Pyrazinamide PLA nanoparticles
Single dose resulted in therapeutic levels in
plasma for 6-8 days and in lungs up to 11 days
Rifampicin +
Isoniazid +
Pyrazinamide
Crystalline spherical
microparticles
Combination drugs gave better stability than
individually spray-dried antibiotics
Table 2. Dry powder inhalers of anti-TB drug combinations.

10.  TECHNIQUES USED FOR PRODUCTION OFTECHNIQUES USED FOR PRODUCTION OF
ANTI-TB FORMULATIONSANTI-TB FORMULATIONS
Spray drying
Recrystallization and spray drying
Supercritical/near-critical microparticle formation
Freeze drying
Spray drying and freeze drying
Thin film hydration method
Emulsion/Lyophilization
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11.  APPROACHES FORAPPROACHES FOR DPIDPI FOR TUBERCULOSISFOR TUBERCULOSIS
o High Dose Delivery
carrier-based dry powder inhalers
by high loading of microparticles
dry coating of drug with magnesium stearate
oTargeted Delivery to AM
PLGA microspheres
Liposomes
o Extended Release
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12.  CHALLENGES FOR DEVELOPINGCHALLENGES FOR DEVELOPING DPIDPI FORFOR
TB PATIENTSTB PATIENTS
Although considerable research has involved a large
number of drugs to develop dry powder inhalers for treating
TB patients, there is no marketed anti-TB DPI as yet.
In both formulations and devices.
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•Although the engineering of
particles has shown increased
dose delivery, more research
needs to be conducted to have
a powder which is stable and
offers high dispersion
capacity.
•There are challenges associated
with delivery devices. For
example, inconsistent delivery
from the device may result in
variability in available drugs at
the site of infection that may
lead to resistance.

13.  CONCLUSIONCONCLUSION
Tuberculosis treatment has become complicated due to
the emergence of the MDR, XDR and TDR strains of
Mycobacterium tuberculosis.
Pulmonary delivery of anti-TB drugs is a method to
provide local high drug concentration with lower drug
dose compared to oral and parenteral doses.
Dry powder formulations for inhalation are more stable
than solutions or suspensions and are capable of delivering
the high doses of drugs required to treat TB.
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14.  REFERENCESREFERENCES
1. Shyamal Das, Ian Tucker and Peter Stewart. Inhaled Dry
Powder Formulations for Treating Tuberculosis. Current
Drug Delivery, 2015, 12, 26-39
2. A. Misra et al. review Inhaled drug therapy for treatment
of tuberculosis/Tuberculosis 91 (2011) 71e81.
3. Yadav A.B., Singh A.K., Verma R.K., Mohan M.,
Agrawal A.K., Misra A. The devil's advocacy: When and
why inhaled therapies for tuberculosis may not work.
Tuberculosis, 2011, 91, 65-66.
4. World Health Organization. Definitions and reporting
framework for tuberculosis revision. 2012.
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15. HAVE A NICE DAY
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