As drug discovery continues to generate poorly water-soluble molecules, there is a growing need for formulation techniques that can improve drug solubility. Liquid formulations containing lipids, solvents, or surfactants are often used in combination to improve drug solubility and bioavailability. The final formulation can be filled into hard gelatin capsules by means of a piston pump system as a room-temperature liquid or as a molten semi-solid.

    The filling of liquid or semisolid formulations depends on the viscoelasticity of the formulation and the need to meet certain properties at the filling temperature. As a general rule, the viscosity of the formulation should be between 50 and 1000 centipoise (cP) (although higher viscosity formulations may be suitable for manufacture) and should not exceed 70 °C.

    Ideally, the particle size in the suspension should be less than 20 µm, and the formulation should ensure no stringing, dripping, splashing, or curing of the formulation at the metering nozzle. Unless the filled hot melt is fully cured below 40 °C, it is recommended to tape or weld hard capsules using a separate tape seal or Liquid Encapsulation Microspray Seal (LEMS) sealing equipment.

    But if hard gelatin capsules cannot be used for any formulation, preference, or cultural reasons, then empty HPMC capsules can be made using alternative materials such as polymer shells or hypromellose.