Application of organogels as oral controlled release formulations of hydrophilic drugs

• Published in: International journal of pharmaceutics 2012-10, Vol.436 (1-2), p.869-872
• Main Authors: Iwanaga, Kazunori, Kawai, Mineo, Miyazaki, Makoto, Kakemi, Masawo
• Format: Article
• Language: English
• Subjects: Animals; Antipyrine - administration & dosage; Antipyrine - chemistry; Antipyrine - pharmacokinetics; Controlled release; Delayed-Action Preparations - administration & dosage; Delayed-Action Preparations - chemistry; Delayed-Action Preparations - pharmacokinetics; Drug Administration Routes; Drug delivery system; Gels; Hydrophilic drugs; Hydrophobic and Hydrophilic Interactions; Ibuprofen - administration & dosage; Ibuprofen - chemistry; Ibuprofen - pharmacokinetics; Intestinal absorption; Male; Ofloxacin - administration & dosage; Ofloxacin - chemistry; Ofloxacin - pharmacokinetics; Organogel; Rats; Rats, Wistar; Solubility; Soybean Oil - chemistry; Stearic Acids - chemistry; Suspensions; Theophylline - administration & dosage; Theophylline - chemistry; Theophylline - pharmacokinetics
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2012.06.041

We previously demonstrated that organogels prepared from soybean oil using 12-hydroxy stearic acid as a gelator can slowly release ibuprofen, a model lipophilic drug. In this study, we investigated the applicability of organogels as controlled release formulations of hydrophilic drugs. The release rates of theophylline and ofloxacin, which are used as model hydrophilic drugs, were significantly slower than those of ibuprofen and antipyrine (model lipophilic drugs). Furthermore, no erosion was noted during drug release from organogels. Lipophilic drug molecules are released after diffusion in organogels because all molecules fully dissolve in the gel. On the other hand, hydrophilic drug molecules need to be dissolved before they diffuse in the organogel, prior to their release from the gel. Therefore, it is speculated that the release rates of hydrophilic drugs are slower than those of lipophilic drugs. To confirm the usefulness of organogels in controlled release formulations in vivo, organogels containing ibuprofen, ofloxacin, theophylline or antipyrine were intraduodenally administered to rats. All drugs used in this study were rapidly absorbed when administered in aqueous suspensions. In contrast, the drug concentrations in plasma after administration in organogels were lower; however, the lower concentrations of drugs sustained for 10h after administration. With organogel administration, the mean residence time of drugs was longer than that with aqueous suspension administration. In conclusion, organogels are potential candidates for controlled release formulations of not only lipophilic drugs, but also hydrophilic drugs.