Understanding the effect of lipid formulation loading and ethanol as a diluent on solidification of pitavastatin super-saturable SNEDDS using factorial design approach

Abstract

Solidification of a preconcentrate lipid formulation namely self-nano emulsifying drug delivery system (SNEDDS) is required to achieve feasibility, flexibility, and a new concept of “dry nano-emulsion”. The purpose of this study was to assess the effect of SNEDDS loading and ethanol as a diluent on the solidification of pitavastatin supersaturable SNEDDS (S-SNEDDS). A 22 full factorial design approach with a center point addition as a curvature was implemented to determine the effect of S-SNEDDS loading and ethanol on the physical characteristics, namely flowability, compactibility, and drug release behavior. Vibrational spectra, thermal behavior, and morphology of solid S-SNEDDS formulation were also evaluated. The results indicated that there was no interaction between S-SNEDDS and carrier, based on vibrational spectra. However, thermal behaviors (enthalpy and weight loss) were depending on SNEDDS loading. Thereafter, the ethanol as a diluent of preconcentrated formulation had no effect on the morphology of carrier structure. However, the S-SNEDDS loading altered the structure of carrier owing to either solubilization or abrasion processes. The statistical model suggested that ethanol as diluent reduced the flowability, compactibility, and drug releases. Meanwhile, the liquid SNEDDS loading affected the reducing of flowability and compactibility. Finally, solidification without diluent and 20% lipid formulation load was recommended. In addition, it was very useful because of ease on handling, flexibility for further formulation, and desired characteristics of final solid dosage form.

Rational Design and Development of a Soluble Mesoporous Carrier for the Solidification of a Preconcentrated Self-Nanoemulsion Formulation

“…The larger pore size and pore volume made it easy to incorporate the liquid preconcentrated formulation into mannitol mesoporous . Pore size determines the liquid incorporation rate into mesoporous material, and pore volumes govern the amount of liquid formulation loaded into mesoporous mannitol. , The pore size and pore volume of mesoporous mannitol were 12.5–310.6 nm and 7.8–65.3 × 10 –3 cm 3 /g, respectively. Different solid loadings on mannitol mesoporous preparation had similar patterns, both Ac and Sc as TA (Figure a).…”

“…Therefore, the drug release response mimics the formation of nanodroplets. Owing to the soluble characteristics of mannitol, it would be easier to dissolve when it was introduced into the water, followed by a self-emulsifying mechanism. , Drug release profiles of sSSNE using Sc and Ac as TAs are presented in Figure a,b, respectively. The drug release profile was different, particularly in the early times.…”

“…Mannitol is a soluble sugar along with no hygroscopic characteristic, which can be modified physically or chemically as a carrier for SSNE. , Owing to the characteristic, it will be accessible to be incorporated into the carrier without any humid adsorbing onto the surface of the carrier. , However, several soluble and biocompatible materials, namely, lactose, can also be applied as carriers . Physical modification through particle engineering increases the efficiency of SNE solidification due to the surface area required for absorption/adsorption of SNE into/on the carrier . Either absorption or adsorption is very dependent on the carrier interaction.…”

“…Therefore, this should be investigated thoroughly. On the other hand, modification through a porous system might alter the physicomechanical characteristics, namely, powder flow and compaction behavior . Hence, the aim of this work was to develop mannitol mesopores using a factorial design approach as a simultaneous assessment and optimization process followed by loading of supersaturated self-nanoemulsion (SSNE) in order to obtain solid SSNE (sSSNE).…”

Development and characterization of a nano-drug delivery system containing vasaka phospholipid complex to improve bioavailability using quality by design approach

“…NDDS has emerged as the most promising innovation strategy ( 6 )to entrap the active constituents inside the lipid layer. They deliver the drug at a rate directed by the requirements of the body, over a period of treatment and potential target of the active compound of an herbal drug to the site of action in a controlled manner to avoid repeated dosing ( 7 8 ).…”