Biopharmaceutics of 13-cis-retinoic acid (isotretinoin) formulated with modified β-cyclodextrins
| Autor: | Wendy Wen Yi Leong, Paul C. Ho, Sui Yung Chan, Jie An Yang, Hai-Shu Lin, Pei Lee |
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| Rok vydání: | 2007 |
| Předmět: |
Male
Vitamin medicine.drug_class Chemistry Pharmaceutical Drug Compounding Retinoic acid Administration Oral Biological Availability Pharmaceutical Science Absorption (skin) Pharmacology Methylation Excipients Rats Sprague-Dawley chemistry.chemical_compound Pharmacokinetics Oral administration medicine Animals Retinoid Isotretinoin Drug Carriers beta-Cyclodextrins Water 2-Hydroxypropyl-beta-cyclodextrin Rats Bioavailability Solubility chemistry Carboxymethylcellulose Sodium Injections Intravenous Dermatologic Agents medicine.drug |
| Zdroj: | International Journal of Pharmaceutics. 341:238-245 |
| ISSN: | 0378-5173 |
| DOI: | 10.1016/j.ijpharm.2007.03.050 |
| Popis: | 13- cis -Retinoic acid (13- cis -RA), also known as isotretinoin, is commonly used in the management of severe acne. Its clinical efficacy in oncology has also been documented. As a vitamin A derivative, it is not soluble in water. This solubility barrier not only affects its oral absorption but also makes parenteral delivery difficult. Recently, water-soluble formulations of 13- cis -RA have been attempted with 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) and randomly methylated-β-cyclodextrin (RM-β-CD). In this study, the pharmacokinetic profiles of these two formulations were assessed in Sprague–Dawley rats after single intravenous or oral administration. We found that 13- cis -RA was eliminated from the body through a dose-independent process after intravenous injection of either sodium salt or the HP-β-CD formulation within the tested dosage range (2.0–7.5 mg/kg). Furthermore, HP-β-CD did not alter the kinetic profile of 13- cis -RA after intravenous administration in comparison with 13- cis -RA sodium salt. We also found that RM-β-CD dramatically enhanced the oral absorption of 13- cis -RA. At 10.0 mg/kg, the bioavailability of 13- cis -RA formulated with RM-β-CD was about three-fold higher than that of the control (13- cis -RA suspended in 0.5% carboxymethylcellulose (CMC)). Similarly, the oral absorption of 13- cis -RA was not saturated within our tested range (2.5–10.0 mg/kg) and the bioavailability remained unchanged. These results demonstrated that HP-β-CD and RM-β-CD were suitable excipients for the delivery of 13- cis -RA. |
| Databáze: | OpenAIRE |
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