Enhancement of the dissolution rate and oral absorption of a poorly water soluble drug by formation of surfactant-containing microparticles

• Published in: International journal of pharmaceutics Vol. 317; no. 1; pp. 61 - 68
• Main Authors: Wong, S.M., Kellaway, I.W., Murdan, S.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 06-07-2006; Elsevier
• Subjects: Animals; Biological and medical sciences; Dissolution; General pharmacology; Griseofulvin; Griseofulvin - blood; Griseofulvin - chemistry; Griseofulvin - pharmacokinetics; Intestinal Absorption; Male; Medical sciences; Microparticles; Oral bioavailability; Particle Size; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Poloxamer - chemistry; Poor solubility; Rats; Rats, Wistar; Solubility; Spray drying; Surface-Active Agents - chemistry; Technology, Pharmaceutical - methods; Water - chemistry; Poor solubility; Spray drying; Oral bioavailability; Griseofulvin; Dissolution; Microparticles; Drug; Pharmaceutical technology; Solubility; Oral administration; Bioavailability; Surfactant; Spiran; Water soluble compound; Antibiotic; Antifungal agent; Absorption; Water solubility; Microparticle; Pharmacokinetics; Physicochemical properties
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2006.03.001

The slow dissolution rate exhibited by poorly water-soluble drugs is a major challenge in the drug development process. Following oral administration, drugs with slow dissolution rates generally show erratic and incomplete absorption which may lead to therapeutic failure. The aim of this study was to improve the dissolution rate and subsequently the oral absorption and bioavailability of a model poorly water-soluble drug. Microparticles containing the model drug (griseofulvin) were produced by spray drying the drug in the absence/presence of a hydrophilic surfactant. Poloxamer 407 was chosen as the hydrophilic surfactant to improve the particle wetting and hence the dissolution rate. The spray dried particles were characterized and in vitro dissolution studies and in vivo absorption studies were carried out. The results obtained showed that the dissolution rate and absolute oral bioavailability of the spray dried griseofulvin/Poloxamer 407 particles were significantly increased compared to the control. Although spray drying griseofulvin alone increased the drug's in vitro dissolution rate, no significant improvement was seen in the absolute oral bioavailability when compared to the control. Therefore, it is believed that the better wetting characteristics conferred by the hydrophilic surfactant was responsible for the enhanced dissolution rate and absolute oral bioavailability of the model drug.