Lipid-Based Formulations - Pharmaceutical Technology

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PharmTech Europe

Lipid-Based Formulations
A new solubilization technology


Pharmaceutical Technology Europe
Volume 24, Issue 9

Some Poloxamers also exhibit precipitation inhibitory effect in the tested compounds. Studies showed that Poloxamer 407 (rebranded to Kolliphor® P407) and Poloxamer P338 (rebranded to Kolliphor® P338) inhibited the compound precipitation in the simulated intestinal fluid (SIF) at concentrations below their CMCs 9. Combinations of Kolliphor® P407 or Kolliphor® P338 with Vitamin E TPGS (rebranded to Kolliphor® TPGS) showed significantly stronger inhibitory effects on the tested compound than the individuals, indicating synergistic effects on inhibition of drug precipitation 10. The lead formulation comprising Kolliphor® P407 maintained the tested compound concentration at 300 μg/mL upon dilution in SIF for at least two hours compared with the compound alone at less than1 μg/mL of its concentration, and increased oral bioavailability significantly (11).

Despite much effort on lipid-based formulations, the success of commercial products is limited to a few active pharmaceutical ingredients. The complexity of such formulation and product development requires extra efforts. Also, the effect of excipients on the bioavailability of the lipid based formulations is highly complex; the in vivo performance of such formulations is poorly predictable. Furthermore, excipients with both acceptable toxic profile and high solubilization capacity for lipophilic drugs are limited. Very often a large amount of surfactants and co-solvents are needed in order to achieve the targeted dose level and to form stable microemulsions. Such a large quantity of excipients might raise safety concerns or compromise shelf-life stability of the products in the lipid base formulations.

Solid dispersion

A solid dispersion is a homogeneous mixture of one or more active ingredients in an inert carrier at the solid 12. It can be classified into simple eutectic mixtures, solid solutions and glass solutions. Solid dispersion approach, in particular, formation of glass solutions of poorly soluble compounds using amorphous excipients with high glass transition temperatures (Tg), has been used to increase dissolution rate and solubility of low solubility compounds for improved oral absorption. Recently several poorly water soluble drugs with solid dispersion formulation approach have been successfully launched in the market.

The strategy of solid dispersion approach is to a) convert crystalline drug into to amorphous one, b) disperse the drug in a hydrophilic excipient carrier at molecular level. Such transformation leads to generation of amorphous glass solution, improved wetting, and reduced particle size of the components to the molecular level, which contributes to increased drug dissolution rate and solubility. To achieve this goal, selection of excipients is crucial.

First of all, excipient miscibility with the drug is important. Excipients must be miscible with the drug in such that the drug can be either molecularly dispersed or form an amorphous precipitate into its excipient matrix. A glass solution will not form if the drug and excipient are immiscible at the tested ratio. The drug/excipient miscibility can be assessed by DSC or predicated with Hansen solubility parameters in some cases. In addition to type of excipients, miscibility of the drug with excipients is dependent on the excipient/drug ratio in the formulation.


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