Water Migration from Soft Gelatin Capsule Shell to Fill Material and its Effect on Drug Solubility

Abstract

The bioavailability of some poorly water-soluble drugs was reported to increase due to a change in dosage form from a tablet to a solution encapsulated in soft gelatin capsules. However, the objective of increasing the bioavailability may be defeated if the drug crystallizes from a solution inside the capsule. In this study, a water-insoluble drug [a-pentyl-3-(2-quinolinylmethoxy)benzenemethanol; REV 5901] was solubilized in both polyethylene glycol 400 (PEG 400) and a 6:1 mixture of Gelucire 44/14:PEG 400. The solutions were then encapsulated in soft elastic gelatin capsules with a fill weight of 700mg (drug, 125mg), and water migration from the capsule shell into the fill material and its effect on the solubility of the drug were investigated. Gelucire 44/14 is a mixture of hydrogenated fatty acid esters with a mp of 44μC; PEG 400 was added to reduce the mp of solution to ˜36°C for easier encapsulation. After equilibration of capsules at ambient condition, the amount of water in the PEG 400 solution was 6.3%. This reduced the solubility of the drug by 45%, resulting in drug crystallization. The solubility decreased exponentially with the increase in water content. The water in the encapsulated Gelucire:PEG solution was only 1.1%, which did not affect the solubility significantly.