Self-microemulsifying drug delivery system

Self-microemulsifying drug delivery system (SMEDDS) is a technology used in pharmacology and pharmaceutical sciences to improve the bioavailability of drugs. It is particularly beneficial for drugs that are poorly soluble in water, which is a common issue that limits the effectiveness of many compounds. SMEDDS are isotropic mixtures of natural or synthetic oils, surfactants, and solvents which can spontaneously form a fine oil-in-water emulsion when exposed to gastrointestinal fluids, with gentle agitation provided by the stomach and intestines.

Overview

The principle behind SMEDDS is to increase the solubility and stability of drugs by incorporating them into an oil-based system that can readily form a microemulsion upon contact with an aqueous environment. The microemulsion formed is typically in the size range of 100 to 250 nanometers, which facilitates the absorption of the drug through the gastrointestinal tract and into the bloodstream, thereby enhancing its bioavailability.

Components

A typical SMEDDS formulation consists of:

• Oil phase: The oil phase can include medium-chain triglyceride oils or other oils that are digestible and can dissolve a significant amount of the lipophilic drug.
• Surfactant: Surfactants are critical for reducing the interfacial tension between the oil and water phases, allowing for the formation of a stable microemulsion. High HLB (hydrophilic-lipophilic balance) surfactants are commonly used.
• Co-surfactant: Co-surfactants, often alcohols with medium chain lengths, help in further reducing the interfacial tension and in stabilizing the microemulsion droplets.
• Drug: The active pharmaceutical ingredient (API) is dissolved in the oil phase.

Mechanism of Action

Upon oral administration and contact with the aqueous environment of the GI tract, the SMEDDS spontaneously forms a microemulsion. The surfactant and co-surfactant in the formulation reduce the surface tension at the oil-water interface, facilitating the formation of micro-sized emulsion droplets. This microemulsion enhances the surface area for drug absorption, promotes the solubilization of the drug in the gastrointestinal fluids, and can improve the permeability of the drug across the intestinal epithelium.

Advantages

• Improved bioavailability of poorly water-soluble drugs
• Enhanced solubility and stability of the drug
• Potential for reduced variability in drug absorption
• Ease of manufacture and scale-up
• Improved patient compliance due to oral dosage form

Limitations

• Potential for drug precipitation upon dilution in the GI tract
• Stability issues with certain formulations
• Requirement for high concentrations of surfactants, which may cause irritation or toxicity
• Compatibility issues between drug and excipients

Applications

SMEDDS have been applied in the formulation of a wide range of drugs, including those used in the treatment of cancer, cardiovascular diseases, and infectious diseases, among others. They are particularly useful for drugs with poor aqueous solubility and those that undergo extensive first-pass metabolism.