What happens when a drug has strong therapeutic potential but cannot dissolve well enough for the body to absorb it effectively? This is a key challenge in developing oral medicines. Oral bioavailability refers to the proportion of an administered dose that reaches systemic circulation unchanged. [1]
For many poorly soluble drugs, limited aqueous solubility can slow dissolution in gastrointestinal fluids, restricting the amount of drug available for absorption. However, improving drug solubility alone does not guarantee better absorption, as permeability, stability and other physiological factors also influence drug performance. [2]
Pharmaceutical scientists therefore use modern formulation approaches to address these challenges and optimise drug delivery. Strategies such as particle-size reduction, amorphous solid dispersions and lipid-based formulations can improve dissolution and, depending on the drug, potentially enhance oral bioavailability [3]. Understanding these approaches helps developers make informed formulation decisions, improve product performance and address the challenges associated with delivering poorly soluble compounds through oral dosage forms.
After oral administration, a tablet breaks apart and the drug dissolves in gastrointestinal fluids before becoming available for absorption. If a drug dissolves poorly, less may be available to enter the bloodstream, potentially reducing its oral bioavailability. However, drug absorption also depends on factors such as intestinal permeability and stability [4].
The Biopharmaceutics Classification System (BCS) categorises drugs according to their solubility and intestinal permeability, helping scientists identify formulation challenges [5].
| BCS class | Solubility | Permeability |
|---|---|---|
| Class I | High | High |
| Class II | Low | High |
| Class III | High | Low |
| Class IV | Low | Low |
BCS Class II drugs are particularly relevant because they have low solubility but high permeability. Although they can cross the intestinal membrane once dissolved, their slow dissolution may limit the amount available for absorption. Therefore, improving dissolution is an important formulation goal for these drugs.
Poor aqueous solubility can make it difficult for the body to absorb enough of a drug after oral administration. For pharmaceutical developers, this can create several challenges:
The challenge is not always the drug molecule itself. In some cases, the right formulation strategy can improve how the drug dissolves and becomes available for absorption. However, the most suitable approach depends on the drug's individual properties.
Several formulation techniques can help poorly soluble drugs dissolve more effectively. The choice depends on the drug’s properties, stability and intended dosage form.
Reducing the size of drug particles can increase their surface area, allowing them to dissolve faster in gastrointestinal fluids.
Key approaches include:
However, smaller particles do not guarantee improved bioavailability in every case.
Many drugs have a crystalline structure, in which molecules are arranged in an organised pattern. An amorphous form has a less ordered structure and may dissolve more readily.
Some poorly soluble drugs can be incorporated into oils or other lipid-based ingredients to help keep them dissolved during digestion.
Nanotechnology can help improve the dissolution of poorly soluble drugs.
The most suitable approach depends on the drug’s chemical properties and the performance required from the final formulation.
Supersaturation occurs when a formulation temporarily creates a higher concentration of dissolved drug than its normal equilibrium solubility. This can help make more drug available for absorption. However, the dissolved drug may form solid particles again through a process called precipitation, reducing the amount available for absorption [11].
To address this challenge, formulation scientists may use precipitation inhibitors, such as certain polymers, to help keep the drug dissolved for longer. This approach may improve oral bioavailability when it is suitable for the drug and formulation.
Developing effective oral medicines involves balancing drug performance, patient needs and manufacturing requirements.
Key considerations include:
For pharmaceutical companies such as Novumgen, these developments highlight the importance of combining formulation science with patient needs to support modern oral drug development.
Oral bioavailability can be improved by using formulation strategies that enhance drug dissolution and solubility. These include particle-size reduction, amorphous solid dispersions, lipid-based formulations and nanotechnology. The most suitable approach depends on the drug’s properties, stability and formulation requirements.
Common techniques include micronisation, nanonisation, amorphous solid dispersions, lipid-based formulations and nanosuspensions. These approaches can improve dissolution, but their effectiveness depends on the drug’s physicochemical properties and the selected formulation.
Drug solubility refers to a drug’s ability to dissolve in a liquid, while oral bioavailability is the proportion of an administered dose that reaches systemic circulation unchanged. Improved solubility can support absorption, but permeability, stability and other physiological factors also influence bioavailability.
Amorphous solid dispersions incorporate a drug in a less ordered, non-crystalline form within a carrier, often a polymer. This can improve apparent solubility and dissolution, potentially increasing the amount of drug available for absorption. Maintaining physical stability and preventing recrystallisation during storage are important formulation challenges.
Lipid-based formulations incorporate poorly soluble drugs into oils or other lipid-based ingredients to help maintain drug solubilisation during digestion. Self-emulsifying drug delivery systems (SEDDS) form fine oil-in-water emulsions in gastrointestinal fluids, potentially supporting absorption. Their performance depends on the drug, formulation composition and digestion process.
Improving oral bioavailability requires more than increasing drug solubility. Modern formulation strategies, including particle-size reduction, amorphous solid dispersions and lipid-based formulations, can help poorly soluble drugs dissolve more effectively and potentially improve absorption. However, the right approach depends on the drug’s properties, stability and manufacturing requirements.
As pharmaceutical science advances, combining formulation innovation with patient-centred dosage-form design remains essential. For Novumgen, this highlights the importance of developing oral medicines that consider both pharmaceutical performance and patient needs.