Fusion Method for Solubility and Dissolution Rate Enhancement of Ibuprofen Using Block Copolymer Poloxamer 407

Abstract

ABSTRACT. Aim of current research was to prepare ibuprofen-poloxamer 407 binary mixtures using fusion method and characterize them for their physicochemical and performance properties. Binary mixtures of ibuprofen and poloxamer were prepared in three different ratios (1:0.25, 1:0.5, and 1:0.75, respectively) using a water-jacketed high shear mixer. In vitro dissolution and saturation solubility studies were carried out for the drug, physical mixtures, and formulations for all ratios in de-ionized water, 0.1 N HCl (pH = 1.2), and phosphate buffer (pH = 7.2). Thermal and physical characterization of samples was done using modulated differential scanning calorimetry (mDSC), X-ray powder diffraction (XRD), and infrared spectroscopy (FTIR). Flow properties were evaluated using a powder rheometer. Maximum solubility enhancement was seen in acidic media for fused formulations where the ratio 1:0.75 had 18-fold increase. In vitro dissolution studies showed dissolution rate enhancement for physical mixtures and the formulations in all three media. The most pronounced effect was seen for formulation (1:0.75) in acidic media where the cumulative drug release was 58.27% while for drug, it was 3.67%. Model independent statistical methods and ANOVA based methods were used to check the significance of difference in the dissolution profiles. Thermograms from mDSC showed a characteristic peak for all formulations with T peak of around 45°C which suggested formation of a eutectic mixture. XRD data displayed that crystalline nature of ibuprofen was intact in the formulations. This work shows the effect of eutectic formation and micellar solubilization between ibuprofen and poloxamer at the given ratios on its solubility and dissolution rate enhancement.

Novel On-Demand 3-Dimensional (3-D) Printed Tablets Using Fill Density as an Effective Release-Controlling Tool

“…Pure crystalline API, polymers, API-polymer physical mixtures (PM), and manufactured amorphous solid dispersions were subjected to mDSC (DSC Q20, TA ® instruments, New Castle, DE, USA) analysis to identify their solid state and important thermal events [ 31 ]. Approximately, 5–15 mg of the samples were weighed in standard DSC aluminum pans and sealed using standard aluminum lids (DSC consumables incorporated, Austin, MN, USA) using a calibrated balance.…”

Solubilization of ibuprofen for freeze dried parenteral dosage forms

“…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).…”

Influence of Poloxamer 407 on Surface Properties of Aqueous Solutions of Polysorbate Surfactants

“…Therefore, it could be envisioned that in order to improve interfacial properties of PS, or reduce the amount of their usage in pharmaceutical formulations, another surfactant could be added to their aqueous solution. For this purpose, we have chosen poloxamer 407 (P407), a nonionic triblock copolymer, one of the most frequently used poloxamers in pharmaceutical formulations (Dugar et al, ; Dumortier et al, ; Zhang et al, ). It is a polymer with two hydrophilic, poly(ethylene oxide) (PEO) groups, attached to the central hydrophobic poly(propylene oxide) (PPO) group, giving PEO‐PPO‐PEO structure.…”