Targeting anti-tubercular drugs directly to infected lungs through development of inhalation system would increase high concentration of drug in lungs and eliminate systemic side effects. This strategy would help to treat tuberculosis more effectively, improve patient compliance by reducing dosing frequency, decrease drug resistance and systemic side effects of anti-tubercular drugs.
Entrapment of two anti-tubercular drugs with different solubilities in a single vesicle, sustain release of the drugs from vesicles for long period of time improves the patient compliance by reducing frequency of administrations.
Development of provesicular powders eliminates the stability problems associated with the vesicles in the form of aqueous dispersion i.e. aggregation, increased size of the vesicles by fusion of vesicles during storage, sedimentation, leakage of encapsulated drug, hydrolysis and oxidation of components of the formulation during storage.
The vesicles produced upon hydration of provesicular powder at lungs are endocytosed by macrophages and releases drug intracellularly, effective to kill the intracellular latent bacilli present in the alveolar macrophages.
Entrapment of first line anti-tubercular drug with second line drug improves the chemotherapy of MDR-tuberculosis.
Expected difficulties in the project
Particle size of the provesicular powder is the important characteristic for pulmonary deposition, as the size of the particles plays very important role in the deep lung deposition. So this study aimed to develop proliposomal powders of inhalable particle size by optimizing the spray drying conditions before formulating provesicular powders.
Size of the vesicles produced upon hydration also affects the relative uptake by macrophages.
Entrapment of two drugs i.e. control of the encapsulation of two drugs in aqueous compartment and hydrophobic lamellae which depends upon the size of the aqueous compartment and lamellarity of vesicle. Therefore the composition of the formulation was optimized by applying statistical design to design an optimized formulation which produces sufficient number of vesicles with good entrapment for both drugs.
Plan of Work
The current proposed study include formulation of provesicular dry powder inhalation systems i.e., proliposomal and proniosomal powders for anti-tubercular drugs to improve patient compliance by reducing dosing frequency and shortening of treatment.
The systematic study plan includes the following
1. Literature review to understand the methodology and to update the recent information in the area of proposed work.
2. Procurement of drugs and other excipients etc.
3. Analytical method development (HPLC) of the drugs to be studied.
4. Optimization of processing conditions of spray drying method.
5. Development and evaluation of provesicular dry powder systems i.e. proliposomal powders and proniosomal powders
• Optimization of provesicular powders by statistical design