Preparation and Evaluation of Immediate Release Ibuprofen Solid Dispersions Using Polyethylene Glycol 4000

Abstract

Ibuprofen is a non-steroidal anti-inflammatory drug that has been widely used in the treatment of mild to moderate pain and fever. As its serum concentrations and analgesic effect are correlated, rapid ibuprofen absorption could be a prerequisite for the quick onset of its action. Because of high membrane permeability, extent of ibuprofen absorption approaches up to 100%. Dissolution thus becomes the rate limiting step for absorption, and the quick release of ibuprofen in the gastrointestinal tract following oral administration is desirable.1) Various formulations such as prodrugs, 2) inclusion complexes, 3) microcapsules, 4) etc. of ibuprofen were developed. However, the dissolution rate and the oral bioavailability of ibuprofen from these formulations differed widely, methods were time consuming and costly, and some formulations were bulky with poor flow characteristics and handling difficulties.Solid dispersions (SDs) of poorly water soluble drugs in hydrophilic carrier matrix have been reported to improve their solubility and dissolution rate.5-7) Moreover, they are also proven to enhance their bioavailability by increasing their saturation solubility in gastrointestinal fluids. However, ibuprofen SDs using solvent or solvent-melting method could be problematic because, it might not be always easy to find a common solvent, large volumes of solvents and long duration of heating might be necessary to enable complete dissolution of both components, and the common methods such as vacuum drying, spray-drying, spraying on sugar beads using a fluidized bed coating system, lyophilization etc. used for the removal of organic solvents from SDs could make the process relatively more complicated, tedious and costly. In addition, they might also associate with the solvent related environmental problems. 7) Although, SDs by melting could be problematic (for drugs with higher melting temperature) because of the possible thermal unstability of the components, and the hardening of melts resulting into difficulties in the pulverization for subsequent formulation, in case of ibuprofen because of its low melting temperature, melting at lower temperature using meltable hydrophilic polymers might be feasible.However, the traditional melting methods have been reported to be associated with many processing difficulties such as the temperature and shear rate control, reproducibility, scalability etc. Although for many drugs including ibuprofen, SDs by melt agglomerations in high shear mixers using a hot solution of meltable hydrophilic carriers as a binding solution have been claimed to be advantageous industrially, [6][7][8] they were also associated with many disadvantages e.g., separate melting of polymer with or without drug was an extra step that could make the process complicated and costly, the yield in many cases was low because of the polymer/drug loss while pouring into the powder mix, and the processes themselves were very much similar to the wet granulation method used in tablet manufacturing process, thus making them re...

Physicochemical characterization and in vivo evaluation of flurbiprofen-loaded solid dispersion without crystalline change

“…They were orally administered to rats in each group, respectively. Then, 0.2 mL of blood was collected from the right femoral artery at pre-determined time intervals and centrifuged at 3000 g for 10 min using a centrifuge 5415C (Eppendorf, Hauppauge, NY, USA) (Kim & Yoon, 1995;Li et al, 2008;Newa et al, 2008;Yong et al, 2004). …”

“…Several conventional methods such as melting, solvent evaporation, and solvent wetting method were previously reported to prepare solid dispersions (Leuner & Dressman, 2000). However, the solid dispersion prepared by melting method with high temperature might chemically decompose the drugs (Miller et al, 2007;Newa et al, 2008). In the case of solvent evaporation method and solvent wetting method, the drug in the solid dispersions changed to amorphous form, resulting that the drug might be unstable (Yamashita et al, 2003).…”

Study of paracetamol-containing pastilles produced by melt technology

“…During hot-melt techniques, pharmaceutical auxiliary agents such as polyethylene glycols (PEGs) or polyvinylpyrrolidone [10] have often been applied as meltable carriers [11,12]. Besides PEGs, sugar alcohols are also commonly used to prepare solid dispersions [13].…”

Infrared spectroscopy for analysis of co-processed ibuprofen and magnesium trisilicate at milling and freeze drying

“…23 Freeze drying is a standard process used to stabilize and store the drug products in the pharmaceutical industries. 24 FTIR spectroscopy was monitored to identify the mechanism of interaction [25][26][27] of the carboxylic acid-containing drug ibuprofen with magnesium trisilicate. The interaction study has also been monitored by scanning electron microscopy and differential scanning calorimetry (DSC).…”

“…Ibuprofen solid dispersions prepared using polyethylene glycol 4000 have shown no significant change in FT-IR spectra. 27 …”