Thesis (Ph.D.) - Cairo University - Faculty of Pharmacy - Department of Pharmaceutics

This study aimed to formulate clonazepam (CZ) as intranasal nanocarriers for immediate control of status epilepticus. Nanocarriers generally have the ability to deliver the drug to the brain through olfactory and trigeminal nerves pathways circumventing the blood brain barrier. Chapter I: Formulation of clonazepam loaded polymeric micelles. A three-level three-factor central composite face-centered design (3³ CCFD) was applied for the preparation using thin film hydration technique. The independent variables were; pluronic® P123 concentration (X₁), Pluronics®: drug ratio (X₂) and hydration volume (X₃). The seventeen prepared formulae were evaluated for: Y₁: entrapment efficiency (%), Y₂: particle size (nm), Y₃: polydispersity index , Y₄: zeta potential (mV), Y₅: cumulative clonazepam released after eight hours (%), Y₆: time for the release of 50% of drug (hr) and Y₇: dissolution efficiency. All the responses except particle size and zeta potential were influenced by the studied variables. Optimization was done by maximizing entrapment efficiency, amount released after eight hours and dissolution efficiency and minimizing polydispersity index and time for the release of 50% drug. The highest desirability value obtained was 0.921 and was denoted to: X₁=50%, X₂=40:1 and X₃=10 ml (formula PM7). Differential scanning calorimetery and transmission electron microscopy demonstrated the ability of the optimized formula to incorporate clonazepam. This formula showed good thermodynamic and kinetic stability when stored for 4 weeks at room temperature. Chapter II: Formulation of clonazepam loaded Transferosomes. Full factorial design (FFD) (2² X 3¹) was adopted for the preparation using thin film hydration technique. The independent variables investigated were X₁: edge activator type (sodium deoxycholate and Labrafil®), X₂: lipid: edge activator molar ratio 10:1, 30:1 and 50:1 and X₃: initial drug amount 10 and 20 mg

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