Solubility and dissolution rate of poorly soluble drugs

Improving the solubility and dissolution rate of poorly soluble drugs to enhance their absorption from the gastrointestinal tract (GIT) involves several strategies

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Particle Size Reduction: Reducing the particle size of the drug increases its surface area, which can improve solubility and dissolution rate. Techniques include micronization and nanonization.

Solid Dispersions: Forming solid dispersions by dispersing the drug in a matrix of a water-soluble polymer can enhance solubility. Common carriers include polyethylene glycol (PEG) and polyvinylpyrrolidone (PVP).

Complexation: Using cyclodextrins or other complexing agents to form inclusion complexes with the drug can improve solubility. Cyclodextrins have hydrophobic cavities that encapsulate the drug, enhancing its solubility.

Salt Formation: Converting the drug into a salt form can improve its solubility, especially if the drug is a weak acid or base. Salt forms often have better solubility characteristics than their free base or acid counterparts.

Co-solvents: Using co-solvents such as ethanol, propylene glycol, or polyethylene glycol in the formulation can increase the solubility of poorly soluble drugs.

Surfactants: Incorporating surfactants or emulsifiers can improve solubility by reducing the surface tension and enhancing wettability. Examples include polysorbates and lecithin.

Nanoemulsions or Microemulsions: These systems can increase the solubility and dissolution rate by providing a stable dispersion of the drug in a liquid medium.

Liophilization (Freeze-Drying): Creating a lyophilized form of the drug can enhance solubility and dissolution by producing a porous structure that facilitates rapid dissolution.

Prodrug Approach: Designing prodrugs that are more soluble than the parent drug can improve absorption. The prodrug is then converted into the active form once absorbed.

pH Modification: Adjusting the pH of the formulation to favor the solubility of the drug can be effective, especially for drugs with pH-dependent solubility.

Nanotechnology: Techniques like self-nano emulsifying drug delivery systems (SNEDDS) or nanoparticle formulations can significantly enhance solubility and dissolution.

Gel Formation: Forming gels with polymers can improve the drug's solubility and control its release.

Each method has its own advantages and may be used alone or in combination depending on the specific drug and formulation requirements.