PULMONARY DRUG DELIVERY SYSTEMS OF POSACONAZOLE: DEVELOPMENT AND OPTIMIZATION THROUGH QUALITY BY DESIGN
DOI:
https://doi.org/10.22159/ijap.2024v16i5.51163Keywords:
Posaconazole, Nano-embedded microparticles, Nano-crystallization, Quality by design, InhalationAbstract
Objective: The main objective of this work is a formulation of nano-embedded microparticles of posaconazole for targeted delivery into lungs through pulmonary route.
Methods: Posaconazole Nano-Crystals (PNCs) were developed through quality by design approach. Influences of sonication time, sonication power, stabilizer type and its concentration on the solubility and time for 90% drug dissolution (T90%) of the PNC were studied through central composite design. Nanoembedded Microparticles of Posaconazole (NMPs) were developed by nano-crystallization using surfactants to enhance the solubility of posaconazole and then the optimized PNCs were embedded into lactose matrix to enhance the size through lyophilization to obtain NMPs that were suitable for inhalational administration.
Results: The optimized formulation of PNCs was found to exhibit a particle size of 159.2 nm, solubility of 0.29 mg/ml and T90% of 24.7 min. This optimized PNCs were embedded into lactose using lyophilization. The lyophilized product was sieved to obtain NMPs with a size below 5 µm.
Conclusion: The optimized formulation is highly suitable for delivering the drug to lungs through inhalation in which drug particles reach secondary bronchi where they can dissolve readily to yield PNCs. These PNCs can easily escape into alveolar fluids for immediate local action.
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