• Twitter
  • Twitter
  • Slideshare
  • logo Amatsigroup

Bioavailability enhancement

AmatsiSEPS uses multiple strategies to overcome the major challenge of poor solubility. Improving the poor oral bioavailability of drugs can be achieved using different bioavailability enhancement technologies. AmatsiSEPS primary strategies to increase bioavailability are based on the development of Solid dispersion, Nanonisation and/or S(M)EDDS.

Solid dispersion

One strategy for the improvement of oral bioavailability of poorly water-soluble compounds is the formulation of solid dispersions. Solid dispersions are used to increase the dissolution rate, a limiting factor for the absorption of BCS class II and IV compounds.

A solid dispersion is a dispersion of one or more compound(s) in an inert carrier at solid state, generally a hydrophobic drug in a hydrophilic carrier. The carrier can be either crystalline or amorphous. The drug can be dispersed molecularly, in amorphous particles (clusters) or in crystalline particles. Following factors contribute in the dissolution process: (1) increase in surface area (particle size reduction), (2) improved wettability related to the hydrophilic carrier; and, in case of amorphous solid dispersions, (3) the lack of energy required to break up the crystal lattice.
In fact, drugs are presented as supersaturated solutions after system dissolution, and it is speculated that, if drugs precipitate, it is as a metastable polymorphic form with higher solubility than the most stable crystal form.

AmatsiSEPS has developed a screening tool to determine carrier excipients which maximize the level and stability of supersaturated drug solutions.

In a next step AmatsiSEPS can study different manufacturing processes at different scales.
Solid dispersions can be prepared by a solvent evaporation process:

  • by spray drying the properties of the powder particles may be customized to meet the requirements for further processing into tablets.
  • by fluid-bed coating, the dispersion is coated on inert particles.

Solid dispersions can be prepared by hot melt extrusion.

For characterization of solid dispersions, AmatsiSEPS uses state of the art technologies such as differential scanning calorimetry (MDSC) and X-ray powder diffraction (XRPD).

Nanonisation

Another bioavailability enhancement method is Nanonisation, which can provide an alternative for the formulation of poorly soluble compounds. AmatsiSEPS applies wet media milling technology to formulate poorly water soluble active pharmaceutical ingredients (APIs) as nanocrystalline particles.

Nanosuspensions have a smaller particle size distribution (nanometer-range) of the dispersed API compared to microsuspensions (micrometer-range), which is favourable for the dissolution rate of poorly water soluble APIs because of the increased surface area, and hence can increase the bioavailability. Micrometer-sized API crystals are media milled using Zirconium oxide beads in an aqueous solution stabilized by the addition of polymers and surfactants.

A physically stable suspension of nanometer-sized API crystals is obtained. Nanosuspensions are characterized by particle size (laser diffraction), zeta potential and dissolution. Nanosuspensions are suitable for oral and parenteral (IV, SC, IM) administration. Nanosuspensions can be converted in solid dosage forms, like tablets and capsules, by spray drying or bead layering.

S(M)EDDS

S(M)EDDS or Self (Micro)-Emulsifying Drug Delivery Systems are mixtures of oils and surfactants, ideally isotropic and optionally containing cosolvents, which emulsify spontaneously to produce fine oil-in-water emulsions when introduced into an aqueous phase under gentle agitation. In the gastrointestinal tract self-emulsifying formulations will spread readily, and the digestive motility of the stomach and the intestine will provide the agitation necessary for self-emulsification. S(M)EDDS are a promising formulation strategy for poorly soluble and lipophilic drugs by increasing bioavailability and solubility. S(M)EDDS can be orally administered in soft or hard gelatine capsules.

Based on solubility data of the active pharmaceutical ingredient (API) in different oils, surfactants and cosolvents (preformulation), a S(M)EDDS can be formulated and characterized. SEDDS typically produce emulsions with a droplet size between 100–300 nm while self micro-emulsifying drug delivery systems (SMEDDS) form transparent micro-emulsions with a droplet size of less than 50-100 nm. The efficiency of self-emulsification is evaluated by determining the rate of emulsification, droplet-size distribution and visual assessment.