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Original Article

Development and in vitro evaluation of an oral SEDDS for desmopressin

, , , , &
Pages 2074-2083 | Received 06 Nov 2015, Accepted 13 Jan 2016, Published online: 29 Feb 2016

Figures & data

Figure 1. Anionic surfactants capable of precipitating desmopressin from aqueous solution. The surfactants likely formed an ion pair with the positively charged guanidine group.

Figure 1. Anionic surfactants capable of precipitating desmopressin from aqueous solution. The surfactants likely formed an ion pair with the positively charged guanidine group.

Table 1. Classification of lipid-based excipients used in the study.

Figure 2. Hydrophobic ion pairing of desmopressin acetate with sodium octadecyl sulfate (○), sodium stearate (▴), sodium dodecyl sulfate (□), sodium oleate (•), and sodium docusate (▪). After the addition of surfactants, the precipitated desmopressin complex was centrifuged and the amount of remaining peptide in supernatant determined by HPLC. Data are shown as mean ± SD (n = 3).

Figure 2. Hydrophobic ion pairing of desmopressin acetate with sodium octadecyl sulfate (○), sodium stearate (▴), sodium dodecyl sulfate (□), sodium oleate (•), and sodium docusate (▪). After the addition of surfactants, the precipitated desmopressin complex was centrifuged and the amount of remaining peptide in supernatant determined by HPLC. Data are shown as mean ± SD (n = 3).

Figure 3. (A) Partitioning coefficient log P (Capmul 907 P/water) of DES/SOL (•), DES/AOT (▪) and DES/SDS (□). Surfactant solutions were added in a dropwise manner to desmopressin solution to precipitate the peptide-surfactant complex. After 5 min 100 μL of Capmul 907 P was added and the mixture stirred for 30 min. The amount of desmopressin in both phases was determined by HPLC. (B) Zoomed log P (Capmul 907 P/water) for DES/AOT (▪) and DES/SDS (□).

Figure 3. (A) Partitioning coefficient log P (Capmul 907 P/water) of DES/SOL (•), DES/AOT (▪) and DES/SDS (□). Surfactant solutions were added in a dropwise manner to desmopressin solution to precipitate the peptide-surfactant complex. After 5 min 100 μL of Capmul 907 P was added and the mixture stirred for 30 min. The amount of desmopressin in both phases was determined by HPLC. (B) Zoomed log P (Capmul 907 P/water) for DES/AOT (▪) and DES/SDS (□).

Figure 4. Solubility of desmopressin acetate (white bars) and DES/AOT (black bars) in chosen water insoluble lipids and surfactants after 48 h of incubation at 25 °C. Data are shown as mean ± SD (n = 3).

Figure 4. Solubility of desmopressin acetate (white bars) and DES/AOT (black bars) in chosen water insoluble lipids and surfactants after 48 h of incubation at 25 °C. Data are shown as mean ± SD (n = 3).

Table 2. SEDDS formulation development with Capmul 907P as main solvent.

Figure 5. Consumption of 0.1 M NaOH during in vitro digestion of SEDDS formulations F4 (○) and F15 (•) by pancreatic lipase at 37 °C. Data are shown as mean ± SD (n = 3).

Figure 5. Consumption of 0.1 M NaOH during in vitro digestion of SEDDS formulations F4 (○) and F15 (•) by pancreatic lipase at 37 °C. Data are shown as mean ± SD (n = 3).

Figure 6. Degradation of desmopressin acetate (▪), DES/AOT-SEDDS-F15 (•) and DES/AOT-SEDDS-F4 (○) at 37 °C in 50 mM acetate buffer pH 5.5 by reduced glutathione. Data are shown as mean ± SD (n = 3).

Figure 6. Degradation of desmopressin acetate (▪), DES/AOT-SEDDS-F15 (•) and DES/AOT-SEDDS-F4 (○) at 37 °C in 50 mM acetate buffer pH 5.5 by reduced glutathione. Data are shown as mean ± SD (n = 3).

Figure 7. Enzymatic degradation of desmopressin acetate (▪), DES/AOT-SEDDS-F15, (•) and DES/AOT-SEDDS-F4 (○) at 37 °C in 50 mM HEPES buffer pH 7.4 with 2 mM CaCl2 by α-chymotrypsin. Data are shown as mean ± SD (n = 3).

Figure 7. Enzymatic degradation of desmopressin acetate (▪), DES/AOT-SEDDS-F15, (•) and DES/AOT-SEDDS-F4 (○) at 37 °C in 50 mM HEPES buffer pH 7.4 with 2 mM CaCl2 by α-chymotrypsin. Data are shown as mean ± SD (n = 3).

Figure 8. Cell viability rates of Caco-2 cells after incubation for 1 h and 4 h with 0.25% (w/v) and 0.375% (w/v) DES/AOT-SEDDS-F4 and DES/AOT-SEDDS-F15. Data are shown as mean ± SD (n = 3).

Figure 8. Cell viability rates of Caco-2 cells after incubation for 1 h and 4 h with 0.25% (w/v) and 0.375% (w/v) DES/AOT-SEDDS-F4 and DES/AOT-SEDDS-F15. Data are shown as mean ± SD (n = 3).

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