Background: Penetration enhancement of metformin hydrochloride via its molecular dispersion in sorbitan monostearate microparticles is reported. Metformin dispersion in sorbitan monostearate as a carrier was thought to be the basic philosophy to maximize its entrapment in the matrix for maximum penetration effect.
Methods: Drug dispersion in sorbitan monostearate with different theoretical drug contents (TDC) were prepared.
Results: All products showed excellent micromeritics and actual drug content (ADC) increased by increasing TDC. These two features are essential for industry concerning processing and cost. The partition coefficient of the drug products showed huge improvement. This indicates the drug entrapment should be in the polar part of sorbitan monostearate as a special image. The drug entrapment process was also reflected in the drug release process due to the insolubility of the matrix in the dissolution medium. The drug permeation profiles from the different drug-sorbitan monostearate products are overlapped and its permeation parameters (permeation coefficient, total drug permeation percent & drug absorption enhancement percent) are nearly equal. The results of the permeation study by using modified non-everted sac suggested the main driving force for 11 improving the drug paracellular pathway is its dispersion in sorbitan monostearate (special image) and is independent of ADC. Pharmacodynamic of the drug products showed a significant improvement than that from the drug alone at p ˂ 0.05. ANOVA test indicated the insignificant pharmacodynamic difference between the low, middle, and high ADC of the products. There is an excellent point-to-point correlation between the drug permeation percent and the drug pharmacodynamic percent. The total amount of the drug permeation percent is equal to the mean of the total drug pharmacodynamic percent.
Conclusion: The results concluded that the drug permeation driving force via the paracellular pathway is its entrapment in sorbitan monostearate as a special image and it does not depend on ADC. This entrapment mechanism improved the drug pharmacodynamic effect. The technique is simple and the products are easy to process due to having an excellent micromeritics property.