¹Department of Pharmaceutics, Faculty of Pharmacy, Parul University, Vadodara 391760 Gujarat, India
²Department of Pharmaceutics, Faculty of Pharmacy, Sardar Patel College of Pharmacy, Anand 388315 Gujarat, India DOI : 10.29228/jrp.2022.00 According to ICH Q8(R2) guideline, this research presents development of inhaled dry powder of bedaquiline loaded nano-carrier for the treatment of MDR-tuberculosis to mitigate the side effects of marketed oral dosage form. Circumscribed Central composite design was utilised to optimize the bedaquiline fumarate (BDQ) loaded NLCs formulated by solvent injection technique and examine the impact of independent variables such as SP Crodamol ML-MBAL-LQ-(RB), Lipoid S 100 and MyrjTM S 40 on dependent variables such as %drug loading, zeta potential, vesicle size, %entrapment efficiency & %In-vitro drug release (Q12). The optimized formulation gave a sustained drug release up to 12 hrs (97.12% ± 0.89%). It formed a stable emulsion with desired zeta potential (-34.98 mV), high entrapment efficiency (65.42% ± 0.49%), smaller vesicle size (175.51 nm) and sufficient drug loading (18.01% ± 0.14%). Further the BDQ loaded NLCs emulsion was lyophilized using mannitol as lyoprotectant and ethylene glycol as cryoprotectant. The lyophilized cake was sifted from #100 and then to #120 and filled in Red/Transparent coloured size “3” hard gelatin capsule. It had good flow characteristics; maximum drug content & the formulation provided no impedance to BDQ release. In-vitro lung deposition study showed that the inhaled dry powder of BDQ loaded NLCs could be deposited in the deep lung tissue & GSD=1 showed that all the particles were of same size. The minimum inhibitory concentration (MIC) of inhaled dry powder of BDQ loaded NLCs capsule 50 mg was found to be 2 μg/ml which was less than the available marketed dosage form. According to ICH Q1C guideline, the formulation was found stable for 6 month accelerated & long term stability conditions. The inhaled dry powder of BDQ loaded NLCs reduced the peripheral tissue exposure and dosing frequency, gave a target specific action, improved the bioavailability and patient compliance. Keywords : Bedaquiline fumarate; NLCs; DPIs; ICH Q8(R2) guideline; ICH Q1C guideline