Extended Release Felodipine Self-Nanoemulsifying System

Abstract

Abstract. The purpose of the present study was to formulate a self-nanoemulsifying system (SNES) containing model lipophilic drug, felodipine (FLD), to improve its solubility. The SNES was formulated using varying amounts of Miglyol® 840 (as an oil), Cremophor® EL (as a surfactant), and Capmul® MCM (as a co-surfactant). The SNES were characterized for turbidity, droplet size and in vitro FLD release. The SNES containing oil, surfactant, and co-surfactant in the weight ratio of 3.5:1.0:1.0, respectively, showed good emulsification, median droplet size of 421 nm, and rapid FLD release (>90% release in 15 min). Gelling was induced in the SNES by addition of Aerosil® 200 (A 200). Rheological studies clearly demonstrated the formation of gelled microstructure with enhanced elasticity for SNES with A 200. Since FLD warrants extended delivery for management of hypertension, the gelled SNES was further encased within the hydrophobic Gelucire® 43/01 (GEL) coat to extend the release of FLD. Caprol® PGE-860 (CAP) was added to this coat as a release enhancer. No interaction was seen between GEL and CAP in differential scanning calorimetry. The effect of two formulation variables in the encased SNES, viz., the gelling agent (A200) and the release enhancer (CAP), on the in vitro FLD release was evaluated using 3 2 factorial design experiments. CAP by virtue of channel formation in GEL coat favored the FLD release, while the A200 retarded the FLD release by inducing gelling. At later time points, an interaction between these two variables was found to govern extended release of FLD. The developed gelled SNES encased within the GEL coat can be used as an extended release composition for lipophilic drugs.

Flufenamic Acid-Loaded Self-Nanoemulsifying Drug Delivery System for Oral Delivery: From Formulation Statistical Optimization to Preclinical Anti-Inflammatory Assessment

“…Such computational-based techniques help in selecting the important factors which affects the measured responses in the study and dropping the non-significant factors 23 . Moreover, it is also useful in assessing the possible interactions between the factors 24 . The formulation was optimized by full factorial design as 3 2 level independent variables using Design Expert Design Expert 10.0.1, Stat Ease.…”

Design and evaluation of self-nanoemulsifying drug delivery systems for nebivolol hydrochloride

“…If the SNEDDS has very low viscosity, it may enhance the probability of leakage from the capsule and the system with very high viscosity may create problem in pourability. [65] The viscosity value [ Table 6] of formulation <10,000 cps, is generally considered as suitable for developed SNEDDS which can be filled in hard gelatin capsules by commercial liquid filling equipment's. [65] The viscosity values are also known to provide a linking on whether the system is w/o or o/w type.…”

“…[65] The viscosity value [ Table 6] of formulation <10,000 cps, is generally considered as suitable for developed SNEDDS which can be filled in hard gelatin capsules by commercial liquid filling equipment's. [65] The viscosity values are also known to provide a linking on whether the system is w/o or o/w type. [66] It is also reported that viscosity affected the droplet size and rate of drug diffusion.…”

Design and optimization of self-microemulsifying drug delivery system (SMEDDS) of felodipine for chronotherapeutic application

“…The bioavailability of FL is strongly limited by its high lipophilic character (aqueous solubility <0.5 mg/L) (Abrahamsson et al, 1994). Literature reports the chronotherapeutic drug delivery of FL using polyvinyl pirrolidone/hydroxypropyl methylcellulose (PVP/HPMC) nanodispersion which is responsible for bioavailability enhancement of FL (Lemmer, 1991;Evangelos et al, 2006) and also the extended release FL self-nanoemulsifying system (Patil et al,2009). Thus, effective formulation design can be a useful approach which results in improved solubility, absorption and in total oral bioavailability of such drug candidates (Pouton et al, 2006).…”