Mefenamic acid-loaded solid SMEDDS: an innovative aspect for dose reduction and improved pharmacodynamic profile

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Pharmacology

Background:

• Mefenamic acid (MFA) is a non-steroidal anti-inflammatory drug (NSAID) with limited oral bioavailability.
• Improving the pharmacodynamic activity of MFA requires enhanced absorption and therapeutic efficacy.

Purpose of the Study:

• To develop and characterize solid self-microemulsifying drug-delivery systems (S-SMEDDS) of mefenamic acid (MFA).
• To evaluate the in vitro dissolution, in vivo absorption, and pharmacodynamic activity of the developed S-SMEDDS.

Main Methods:

• Solubility studies and pseudoternary phase diagrams were used to optimize liquid self-microemulsifying drug-delivery systems (SMEDDS).
• Optimized liquid SMEDDS were spray-dried to obtain S-SMEDDS.
• Physicochemical characterization included X-ray diffractometry and differential scanning calorimetry.
• In vitro dissolution studies and in vivo pharmacokinetic and pharmacodynamic models (acetic acid-induced writhings, carrageenan-induced paw edema) were performed.

Main Results:

• S-SMEDDS demonstrated enhanced amorphization and molecular dispersion of MFA.
• The optimized S-SMEDDS exhibited significantly improved in vitro dissolution rates compared to pure MFA and a marketed product.
• A multifold enhancement in the absorption profile of MFA was observed with S-SMEDDS.
• Enhanced analgesic and anti-inflammatory activities were confirmed in vivo.

Conclusions:

• The developed S-SMEDDS formulation effectively improves the physicochemical and biological attributes of mefenamic acid.
• S-SMEDDS offer a promising approach for enhancing MFA's therapeutic efficacy and potentially reducing its dosage.
• The study substantiates the potential of S-SMEDDS for improved drug delivery and pharmacodynamic activity.