No abstract

To improve its dissolution, ibuprofen solid dispersions (SDs) were prepared, characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FTIR), and evaluated for solubility, and in-vitro ibuprofen release. Loss of individual surface properties during melting and re-solidification as revealed by SEM micrographs indicated the formation of effective SDs. Absence or shifting towards the lower melting temperature of the drug peak in SDs and physical mixtures in DSC study indicated the possibilities of drug-polymer interactions. FTIR spectra showed the presence of drug crystalline in SDs. The effect of improved dissolution on the oral absorption of ibuprofen in rats was also studied. Quicker release of ibuprofen from SDs in rat intestine resulted in a significant increase in AUC and C(max), and a significant decrease in T(max) over pure ibuprofen. Comparison of the enhanced solubility, dissolution, AUC, and C(max) of ibuprofen from different poloxamers suggested that the preparation of ibuprofen SDs using P 407 as a meltable hydrophilic polymer carrier could be a promising approach to improve its solubility, dissolution and absorption rate.

To improve its solubility, dissolution, and bioavailability; Ibuprofen-polyethylene glycol 8000 (PEG 8000) solid dispersions (SDs) with different drug loadings were prepared, characterized by scanning electron microscopy (SEM) and differential scanning calorimetry (DSC), and evaluated for solubility, in-vitro release, and oral bioavailability of ibuprofen in rats. Loss of individual surface properties during melting and solidification as revealed by SEM micrographs indicated the formation of effective SDs. Absence or shifting towards the lower melting temperature of the drug peak in SDs and physical mixtures in DSC study indicated the possibilities of drug-polymer interactions. Quicker release of ibuprofen from SDs in rat intestine resulted in a significant increase in AUC and C max , and a significant decrease in T max over pure ibuprofen. Preliminary results of this study suggested that the preparation of ibuprofen SDs using PEG 8000 as a meltable hydrophilic polymer carrier could be a promising approach to improve solubility, dissolution and bioavailability of ibuprofen.

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...

Coenzyme Q10 (CoQ10) (Fig. 1), a yellow crystalline powder with a melting point of about 50°C is a lipid soluble vitamin like substance that inhabits inside of the inner mitochondrial membrane where it functions as an integral part of electron transport of oxidative phosphorylation.1) It is used as a nutritional supplement, antioxidant and in the treatment of cardiovascular disorders such as angina pectoris, hypertension, and congestive heart failure. It is practically insoluble in water and poorly absorbed (T max 5-10 h) from the gastrointestinal tract due to its high molecular weight and poor water solubility thereby presenting a challenge in the development of a formulation for oral administration.2) Many approaches for formulating CoQ10 have been reported. Oil based or powder filled capsules and tablet formulations are currently available on the market as nutritional supplements.3,4) However, dissolution and oral bioavailability of these formulations differ widely.5) Other reported formulation strategies include a solubilized system with soy lecithin, 6) a micellar solution of CoQ10 with polyoxyethylene (60) hydrogenated castor oil, 7) lipid microspheres prepared as a soybean oil emulsified with yolk phospholipids, 8) a redispersible dry emulsion, 9) the complexation of CoQ10 with cyclodextrins, 10) self-emulsifying drug delivery systems, 3) and a solubilized form of CoQ10 in a blend of polysorbate 80 and medium chain triglycerides.11) However, dissolution profiles are not reported for most of these formulations either due to their oily nature and poor aqueous solubility or due to the absence of a suitable dissolution medium. Further, these approaches were tedious, time consuming and costly. Thus, there is a great need for an efficient, easy, quick, and costeffective method to improve the solubility and dissolution of CoQ10.Dispersion of poorly water soluble drug in an inert hydrophilic carrier matrix at solid state either by melting or solvent or solvent-melting method leads to products known as solid dispersions (SD) 12,13) that have tremendous potential for improving drug solubility 14,15) because of the drug solubilizing or co-solvent effect of hydrophilic carrier, better wettability and dispersibility of drug by the carrier material, and the formation of amorphous forms of drug and carriers. [12][13][14][15] However, the SDs prepared by high temperature melting, solvent or solvent-melting method etc. are problematic because 1. The high melting temperatures could chemically decompose drugs and carriers, 12) 2. The hardening of melts could lead to difficulties in pulverization for subsequent formulation into an appropriate dosage form, 3. It is difficult to identify a common solvent to dissolve hydrophobic drug and hydrophilic carrier, 4. The large volumes of solvents and heating are necessary to enable complete dissolution of both components. 5. Vacuum drying, 16,17) spray drying, [18][19][20][21] spraying on sugar beads using a fluidized bed-coating system, 22) lyophilization 23) etc. used for the remov...