Release of Cyclobenzaprine Hydrochloride from Osmotically Rupturable Tablets

• Published in: Drug development and industrial pharmacy 2002-01, Vol.28 (6), p.695-701
• Main Authors: Razaghi, Amir M., Schwartz, Joseph B.
• Format: Article
• Language: English
• Subjects: Amitriptyline - administration & dosage; Amitriptyline - analogs & derivatives; Biological and medical sciences; Chemistry, Pharmaceutical; Cyclobenzaprine hydrochloride; Excipients - chemistry; General pharmacology; Medical sciences; Membranes, Artificial; Mercury intrusion porosimetry; Osmotic delivery system; Osmotic Pressure; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Polyethylene Glycols - chemistry; Rupturable tablet; Rupture time; Tablets; Tranquilizing Agents - administration & dosage; Water-swellable polymer
• ISSN: 0363-9045; 1520-5762
• DOI: 10.1081/DDC-120003861

ABSTRACT Osmotically rupturable systems were developed and the release of cyclobenzaprine hydrochloride (model drug) from the systems was investigated. Systems were designed using mannitol (osmotic agent) and increasing amounts of polyethylene oxide (PEO, a water-swellable polymer) surrounded by a semipermeable membrane. When placed in an aqueous environment, osmotic water imbibition into the systems distended and swelled the systems until the membrane ruptured and released the active compound to the outside environment. Tablets with increasing amount of PEO exhibited longer rupture times. This may be due to osmotic pressure-modulating properties of the polymer, changing the rate of water imbibition into the systems. The integrity of the membranes was investigated using high-pressure mercury intrusion porosimetry. Minimal mercury intrusion into the membrane structure and core tablet indicated membrane integrity and lack of defective areas or pinholes. The results were in agreement with the release profiles where no drug release was detected prior to membrane rupture. Mercury intrusion porosimetry appears to be a promising technique for evaluation of membrane integrity. Once the systems ruptured, drug was released by osmotic pumping and diffusion mechanisms through the ruptured area. There was a decrease in drug release rate with inclusion of PEO in the core. The effects of film thickness on rupture and release times were also investigated. Devices with thicker films produced longer rupture times. This is in agreement with the theoretical prediction.