Solubility Enhancement Techniques for BCS Class II Molecules

For BCS Class II drugs, which have low solubility but high permeability, formulation efforts center on enhancing solubility to improve bioavailability. Here’s how we turn API properties into actionable formulation strategies:

Solubility Improvement

With BCS Class II drugs’ low solubility, enhancing solubility is key for bioavailability. Techniques include:

Particle Size Reduction: Reducing particles to the micron or nano scale increases surface area exposed to GI fluids, enhancing dissolution rate. This can be done through milling or high-pressure homogenization.

Solid Dispersions: Using a matrix of water-soluble polymers (e.g., PVP, HPMC) disperses the drug in an amorphous form, which dissolves more readily than crystalline forms. This method works well for drugs with solubility dependent on particle size.

Lipid-Based Carriers: Self-emulsifying systems (SEDDS) or lipid-based carriers keep the drug dissolved in a lipid that emulsifies in the GI tract, aiding in solubility and even enabling lymphatic absorption for lipophilic drugs.


Surfactants & Solubilizers

Surfactants and solubilizers aid in wetting and dispersing BCS Class II drugs, enhancing contact with GI fluids for consistent absorption:

Surfactants: Agents like Polysorbate 80 and Sodium Lauryl Sulfate (SLS) lower surface tension, enabling better penetration of water into drug particles and reducing clumping.

Co-Solvents: PEG, ethanol, and propylene glycol increase solubility by creating a more suitable environment for dissolution. Used with water, they help maintain an ideal solvent system for fast dissolution rates.


pH Adjustments

For pH-sensitive drugs, stable microenvironmental pH is beneficial:

Buffering Agents: Buffers like citric acid or phosphate salts create a stable pH around the drug, helping maintain solubility.

Microenvironmental pH Modifications: Within tablets or capsules, pH can be controlled locally with excipients to sustain solubility throughout the GI tract.


Tailored Formulations

Dosage forms improve delivery by optimizing particle surface area, dissolution, and absorption:

Fast-Disintegrating Tablets: Designed to dissolve on contact with fluids, ensuring rapid drug release, ideal for immediate-release formulations.

Granules and Pellets Encapsulated in Capsules: Coated granules/pellets support controlled or delayed release, which works well for drugs needing gradual release.

Amorphous Forms: Converting the drug from crystalline to amorphous form improves solubility, but stabilizers are used to prevent recrystallization.

These strategies are tailored to overcome BCS Class II solubility challenges, maximizing therapeutic potential by improving solubility, dissolution, and bioavailability.


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Resource Person: Moinuddin syed. Ph.D, PMP®

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