This review describes the use of phospholipid excipients to make Pharmaceutical Form (Dosage Form) Line Extensions of existing drugs as part of a Product Life Cycle Management. Product examples and development candidates, which show the versatility of phospholipids as key excipients in formulations to develop line extension drug products for any administration route by reformulating existing products, are provided. The resulting patented products enable the application of a drug substance for another administration route or show an increased efficacy and/or reduced toxicity of the formulated drug substances, or enable a more convenient use, through reduction of dosing frequency, or adapt a product for regulatory requirements for specific patient populations. Parenteral line extensions for lipophilic drugs using non‐toxic phospholipid‐based solubilising formulations are clearly an alternative to products with solubilising synthetic detergents with the risk for allergic and anaphylactic reactions. This review draws the attention to academic and industrial formulation scientist to consider using phospholipid excipients to reformulate existing products to improve the product properties by an active product life cycle management. Phospholipids are suitable for this purpose because they are biocompatible, biodegradable, non‐toxic, and available at large scale and of pharmaceutical grade. Besides, they are well known to regulatory authorities.

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The basic transport properties of indometacin (INDO) were investigated in human blood polymorphonuclear leucocytes (PMNs) of healthy volunteers. The silicone oil cushion centrifugation method was used as ligand-binding assay for both the measurements of the cellular association of INDO and the intracellular volume. This assay enabled us to calculate the intracellular INDO concentrations. A considerable amount of INDO accumulates in the PMNs to cause cell/medium ratios between 20 and 90. At low INDO levels (1–10 nmol/l) the cell/medium ratio appeared to be higher than at high INDO levels (>2 μmol/l). This finding suggests that the cell accumulation of INDO comprises saturable binding and/or transport components. Scatchard analysis of the association isotherm of INDO after incubation for 60 min at 37 °C reveals apparent K_D values of 3.7 μmol/l (low affinity) and 1.2 nmol/l (high affinity). The number of high-affinity association sites (60 fmol/3 × 106 PMNs) was 1,000–2,000 times lower than the number of low-affinity association sites (103 pmol/3 × 10⁶ PMNs). INDO cell association is suggested to be a net result of diffusive and mediated influx and efflux mechanisms, and of binding to (plasma) membranes. The capacity of the PMN to accumulate INDO is enhanced upon (1) establishment of an inward gradient of [H⁺], and (2) activation of the Na⁺-H⁺ antiport by chemotactic peptide. The possible mechanisms of incorporation of INDO in the PMN are discussed in the scope of the proposed PMN-related anti-inflammatory action of INDO.

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