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. 2021 Oct 11;11(1):20153.
doi: 10.1038/s41598-021-99649-3.

Metformin hydrochloride entrapment in sorbitan monostearate for intestinal permeability enhancement and pharmacodynamics

Omar Y Mady  1 , Adam A Al-Shoubki  2 , Ahmed A Donia  3 , Waseem Qasim  4
Affiliations

Metformin hydrochloride entrapment in sorbitan monostearate for intestinal permeability enhancement and pharmacodynamics

Omar Y Mady et al. Sci Rep. .

Abstract

Penetration enhancement of metformin hydrochloride via its molecular dispersion in sorbitan monostearate microparticles is reported. This represents basic philosophy to maximize its entrapment for maximum penetration effect. Drug dispersion in sorbitan monostearate with different theoretical drug contents (TDC) were prepared. Products showed excellent micromeritics and actual drug content (ADC) increased by increasing TDC. The partition coefficient of the drug products showed huge improvement. This indicates the drug entrapped in the polar part of sorbitan monostearate as a special image which effects on the drug release. The drug permeation profiles from the different products are overlapped with nearly equal permeation parameters. The permeation results suggested the main driving force for improving the drug paracellular pathway is its dispersion in sorbitan monostearate and is independent of ADC. Pharmacodynamic of the products showed a significant improvement than the drug alone at p ˂ 0.05. ANOVA test indicated the insignificant pharmacodynamic difference between the low, middle, and high ADC of the products. An excellent correlation founded between the drug permeation and pharmacodynamic precents. Drug permeation driving force via the paracellular pathway is its entrapment in sorbitan monostearate and independent on ADC. The technique is simple and the products had excellent micromeritics.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Effect of the theoretical drug content on its partition coefficient.
Figure 2
Figure 2
Drug release profile from different prepared drug-span matrices.
Figure 3
Figure 3
The permeability profiles of the pure drug, drug-tween, and different molecular solid dispersions of the drug in sorbitan monostearate matrices.
Figure 4
Figure 4
Histogram representation of the apparent permeability of metformin (M-to-S) from the pure drug, drug-tween, and drug-sorbitan monostearate solid dispersion products.
Figure 5
Figure 5
(A) Profiles of the change in glucose levels percent versus time. (B) Profiles of the change in glucose levels percent versus time (SD error bar).
Figure 6
Figure 6
Point to point (level A) correlation of the drug permeation profiles and its pharmacodynamics effect: (A) metformin HCL; (B) metformin-tween 80; (C) 25% drug in span-tween. (D) 50% drug in span-tween; (E) 75% drug in span-tween.
Figure 7
Figure 7
Profiles of the change in glucose levels percent versus time (SD error bar).
See this image and copyright information in PMC

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