Improving Ibuprofen solubility by surfactant-facilitated self-assembly into mixed micelles

Abstract

Ibuprofen is a poorly water-soluble drug, characterized by dissolution-limited oral bioavailability. One approach to improve its water solubility and bioavailability is by solubilizing it in micellar surfactant solutions. Here we investigate the effect of the surfactant type and the mechanism of solubility enhancement of Ibuprofen in surfactant solutions. The equilibrium Ibuprofen solubility in solutions of six surfactants was determined by HPLC. The nonionic surfactant polysorbate 80 (Tween 80), and the anionic surfactants sodium dodecyl sulfate (SDS) and sodium lauryl ethoxy (3) sulfate (SLES-3EO) improve the Ibuprofen solubility by a factor of 200, as compared to the solubility in water. The highest Ibuprofen solubility is observed in SDS and SLES-3EO solutions, containing 0.6 M NaCl. The mole fraction of Ibuprofen in the micelles and the transfer energy of Ibuprofen molecules from the aqueous phase into the micelle environment were determined by thermodynamic analysis of the solubility data. The maximum Ibuprofen mole fraction in the micelles of all studied surfactants is exceptionally high (between 0.4 and 0.6). Thus we can conclude that the main mechanism of Ibuprofen solubility enhancement is a selfassembly within mixed micelles with the main surfactant. The energy of co-micellization is estimated to be around 14kT per Ibuprofen molecule.

Preparation and investigation of indirubin‐loaded SLN nanoparticles and their anti‐cancer effects on human glioblastoma U87MG cells

“…Despite of better solubility, the biocompatibility and controlled drug release to tumor cells were still challenging. Hence, we prepared Indirubin‐loaded SLNs as a promising anti‐cancer complex using Cetyle palmitate as well‐known lipid in nanoparticle synthesis and polysorbate 80 as a surfactant facilitating penetration across blood brain barrier (BBB) (Stoyanova et al, ).…”

Solubilization of ibuprofen for freeze dried parenteral dosage forms

“…It is a member of the well-established nonsteroidal anti-inflammatory drugs (NSAIDs) and is widely used for acute or chronic pain relief. Due to its poor aqueous solubility (0.12 mg mL -1 at 25 °C) (5) and high dosing (maximum single dose is 800 mg) (7), it presents a great challenge to formulating both solid and liquid dosage forms, and thus also parenteral ones.…”

“…Various techniques for IBP solubilization in solid oral formulations have been described in the literature: lipid based drug delivery system (8), solid lipid nanoparticles or spray drying of amorphous IBP nanoparticles for the production of granules with enhanced drug release (9,10), solubilization by surfactants (7,11), solid dispersion techniques (12,13), fusion method with Poloxamer 407 (14) and also freeze drying to form IBP crystals (15) or for orodispersible tablet (ODT) formulation (16). The approaches described for liquid formulations are mainly focused on solubility enhancement by cyclodextrin complexation (17,18), addition of hydrotropic agents (19), pH modification (7), surfactant and cosolvent addition (20)(21)(22) and salt formation (23,24). Use of co-solvents is by far the most common and effective method, although recently the use of complexing agents such as cyclodextrins has greatly increased owing to their positive effect on drug stability and bioavailability (5).…”

EVALUATION OF ORALLY DISINTEGRATING TABLET OF IBUPROFEN-β-CYCLODEXTRIN INCLUSION COMPLEX

“…This can hamper its oral bioavailability and onset of action. Several approached have been employed to increase IB water solubility and oral bioavailability, such as solid dispersion [3], size reduction [4], copolymer [5], and surfactant [6]. Inclusion complex, especially using cyclodextrin (CD), has been widely used to increase the water solubility of poorly water-soluble drugs as well as enhance bioavailability [7].…”