ENHANCEMENT OF SKIN PERMEABILITY OF ECONAZOLE NITRATE USING NOVEL FLEXISOMAL NANOCARRIERS BY IMPLEMENTING QUALITY BY DESIGN (QBD) APPROACH

Objective: The purpose of this study was an implementation of quality by design (QbD) for the formulation and characterization of econazole nitrate loaded flexisomal nanocarriers (EN-FS) to improve antifungal activity and to enhance skin permeability. Methods: Initially quality target product profile (QTTP) elements were identified and later critical quality attributes (CQA) elements were defined from QTPP elements. Particle size, entrapment efficiency and deformability index were defined as CQAs. Risk assessment was performed by using fishbone diagram and failure mode and effect analysis (FMEA). Design space was created by using fractional factorial design 25-2 as screening design and 32 full factorial design as optimization design to optimize two variables soya phosphatidylcholine concentration(X1) and sodium deoxycholate concentration (X2). Results: Optimized batch of EN-FS was 249.5±3.48 nm, with entrapment efficiency of 88.6±0.89 % and deformability index of 31.75±0.98. Zeta potential analysis showed value of-22.5 mV. Morphological analysis by TEM showed spherical shaped flexisomes, which confirmed the vesicular characteristics. The optimized batch of EN-FS was further made into hydrogels by using sepineo P600 as gelling agent. The % drug diffusion of EN-FS hydrogels had shown 24.68%. With higher skin deposition and higher value of zone of inhibition in antifungal study as compared to plain EN hydrogel. CLSM studies indicated deep penetration of EN-FS in skin layers. Lastly control strategy for EN-FS were developed. Conclusion: It was concluded that EN-FS showed high flexibility and enhanced antifungal activity therefore found to be a potential nanocarriers for drug deposition in skin layers without disturbing skin integrity

IMPLEMENTATION OF QUALITY BY DESIGN (QBD) APPROACH IN FORMULATION AND DEVELOPMENT OF RITONAVIR PELLETS USING EXTRUSION SPHERONIZATION METHOD

Objective: Ritonavir is an antiretroviral drug used for HIV-AIDS treatment. The purpose of this research work was to implement the quality by design (QbD) approach in formulation of ritonavir sustained-release pellets by industrially applied extrusion spheronization technique. Methods: Pellets were prepared by extrusion spheronization method and evaluated for their physicochemical properties. Initially, on the basis of prior knowledge Quality Target Product Profile (QTTP) element was identified and further Critical Quality Attributes (CQA) elements were defined. Risk assessment (RA) was done by two tools as failure mode and effect analysis (FMEA) and fishbone diagram (Ishikawa plot). Placket Burman design was implemented as a screening design using seven high-risk factors (spheronization speed, spheronization time, extrusion speed, drying method, PVP K 30, cross povidone, and solvent). Optimization study was done by 23 full factorial design with three critical factors as (spheronization speed, extrusion speed and PVP K 30). The in vitro drug release was studied in both gastric and intestinal fluids for 12 h using USP Ι apparatus. Control space was established for the sustained release pellets. Results: Among all batches obtained in 23 full factorial design, batch R7 was found to be effective with carr’s index value of 5.281, percentage yield of 69.6%, time required to release 50% drug was 8 h and percent drug release after 12 h was found 83.132 %, R7 batch was selected as optimized batch. Statistical analysis showed model terms were significant. Conclusion: We can conclude that; sustained-release pellets of ritonavir were successfully designed using QbD approach