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Surfactants are well known as permeation enhancers. Span 60 microparticles encapsulating different concentrations of metformin HCl were prepared by using rapid congeal melting technique. Electro-scanning microscope showed smooth surface but less round microparticles. The actual drug content was nearly equal in the different particle sizes of the microparticles. Differential scanning calorimetry results indicated the molecular distribution of the drug molecules with no evidence of drug thermal degradation. The drug release profile from the microparticles has, in each case, burst and there was incomplete drug release. The drug partition coefficient is markedly enhanced as a result of its molecular dispersion in Span 60, indicating the increasing of the drug lipophilicity as a result of its encapsulation in the polar part of the surfactant. Non-everted sac was used to study the drug permeability after solving its critical points. Compared to pure drug, the permeability profile of the drug increased from the Span 60-encapsulated drug, with a total permeation of 68% and drug absorption enhancement of 253%. The drug permeation enhancement mechanism was suggested to be molecular dispersion in the matrix, which is emulsified by Tween 80, and this leads to increasing the hydrophilic paracellular pathway of the drug. Considering the emulsification system of the GIT, which emulsifies the Span 60 instead of Tween 80, a huge improvement of the biopharmaceutics classification system class III permeability and consequently bioavailability could be expected. In addition, this study will open the door to the use of the same technique for enhancing the drug absorption mechanisms by the paracellular pathway for rapid and complete pharmacological effect.

Paracellular Pathway Enhancement of Metformin Hydrochloride via Molecular Dispersion in Span 60 Microparticles