Capryol® 90 is an efficacious intestinal absorption enhancer for insulin in vivo when combined other excipients

The excipient, Capryol® 90, comprises 90 % monoesters of propylene glycol monocaprylate (C₈). With a low hydrophilic lipophilic balance (HLB), lack of aqueous solubility has prevented thorough assessment as an intestinal permeation enhancer for peptides where an expanded range of excipients is needed for oral formulations. Here, we tested whether additional solubilisers, hydrogenated castor oil (HCO-60) or Gelucire® 44/14, could unmask permeation enhancement potential for Capyrol® 90, when co-administered in ex vivo and in vivo rat bioassays. Capryol® 90 (2-16 mg/mL) with and without HCO-60 (1 % (v/v)), or Gelucire® 44/14 (30:70 ratio of Capryol 90®: Gelucire®) were tested using isolated rat colonic mucosae mounted in Ussing chambers. TEER of mucosae decreased by > 80 % within 10 min when Capryol® 90 (8 mg/mL) was presented with HCO-60 or Gelucire®44/14 (16 mg/mL), more than with any of the agents alone. The apparent permeability (P_app) coefficient of the paracellular marker [¹⁴C]-mannitol was increased by 11.7-fold for Capryol® 90 with HCO-60, by 17.1-fold with Capryol® 90 and Gelucire® 44/14, but not by any of the three agents alone. Insulin (50 IU/kg) was then ad-mixed with Capryol® 90 (40 mg/mL) and injected into intact rat jejunal loops with and without HCO-60 (1 % w/v) or Gelucire® 44/14 (30:70 ratio). Large decreases in rat blood glucose levels were observed for insulin when Capryol® 90 was administered with either combination. These glucose reductions were associated with relative bioavailability values for insulin of 4.1 and 3.8 % respectively for Capryol® 90/ HCO-60 (in PBS and FaSSIF) and Capryol® 90/Gelucire® 44/14 (in PBS). In conclusion, Capryol® 90 has potential for use as a permeation enhancer in oral peptide or BCS Class III formulations, but only when enabled by additional solubilisers.