July 26, 2011 -- There are many benefits of controlled drug delivery systems, including sustained release technologies allowing prolonged delivery of a therapeutic dose and time-delayed release providing pulsatile delivery of drug to specific sites.
Temporal control has particular advantages in the treatment of disorders with a circadian pattern, such as cardiovascular disorders, asthma, anxiety and hypercholesterolemia. In such cases, controlled-release formulations can greatly enhance the therapeutic effects of the drug and reduce the dose required. This is particularly beneficial for drugs with a narrow therapeutic window.
Further, there is an expanding body of evidence concerning the relationship between circadian rhythms and the responsiveness of the body to drugs. As a consequence, the absorption, distribution, metabolism and elimination of a drug and its subsequent therapeutic efficacy and/or toxicity can vary considerably with the circadian cycle.
Drug Delivery International (DDi) is a startup formulation development company that specialises in providing solutions for “difficult” formulations, such as those for drugs with poor solubility, poor bioavailability or other properties that prevent APIs from reaching the market or achieving their full therapeutic potential.
DDi, which has an expanding intellectual property portfolio, has developed a series of novel delivery systems, based on compressed tablet technology, that can be readily configured to provide immediate, biphasic or time-delayed sustained drug release profiles. The technology is unique and offers the following advantages:
- Widespread applicability to different drugs and dosages
- A high degree of flexibility in manipulating drug release profiles
- Simple assembly and production processes
- Non pH-sensitive formulations.
These formulations have been developed for sleep maintenance, cardiovascular disease and pain management and clinically evaluated by gamma scintigraphy to visualise the release of the drug. The gamma scintigraphy work was carried out by Bio-Images Research Ltd (Glasgow, UK), a complete clinical research services company which provides clients with early stage guidance in the drug development process.
SLEEP MAINTENANCE
Sleep maintenance insomnia is characterised by frequent and prolonged nocturnal awakenings, typically in the second half of the night. Difficulty in resuming sleep has been associated with reduced sleep quality, leading to anxiety, mood disorders and consequently daytime impairment. DDi has developed a time-delayed hypnotic formulation that provides a two-hour-delayed release of zolpidem for the treatment of sleep maintenance insomnia. Gamma scintigraphy and pharmacokinetic analysis was used to monitor the in vivo performance.
The formulated tablet proved successful in delivering the drug after a predicted time delay. The release parameters were comparable between six subjects, indicating robustness of the formulation in providing accurate time-delayed release. The physiological effects of the sleep tablet coincided with the scintigraphic confirmation of release.
CARDIOVASCULAR
Hypertension has been shown to follow a circadian pattern. Specifically, both heart rate and blood pressure blood pressure peak early in the morning and there can be a marked rise in blood pressure upon awakening called “the a.m. surge”. DDi has developed a formulation for the delivery of anti-hypertensive drugs in the middle of the night, prior to wake-up, when the risk of fatal heart attack is greatest.
This formulation was validated clinically using gamma scintigraphic imaging and pharmacokinetic analysis in six healthy male volunteers, demonstrating delayed sustained release of verapamil in vivo.
PAIN THERAPY
People with rheumatoid arthritis suffer significant problems with pain and stiffness upon awakening. DDi has developed a formulation that provides an immediate night-time release of diclofenac, followed by a seven-hour delay before pulsatile release of a second dose of the drug. This formulation offers immediate pain relief at night time, allowing pain-free sleep, and subsequently provides delivery of pain-relief prior to waking.
COLON TARGETING
Colon targeting is desirable for treatment of diseases specific to the large intestine but the environment in the small intestine and colon in the disease state must be taken into consideration.
DDI COLON DELIVERY TECHNOLOGY
DDi has developed patented technology for time-delayed formulations based on a detailed understanding of the erosion of dosage forms in the GI tract. The barrier layers developed by DDi operate independently of pH and are relatively unaffected by agitation conditions, leading to excellent in vitro/in vivo correlation of erosion performance.
Drug Delivery International Ltd and Bio-Images Research Ltd are part of the Bio-Images Group – providing integrated pharmaceutical development solutions.
Dr Carol Thomson is Chief Operating Officer of Drug Delivery International.
For more information, please contact Dr Carol Thomson on 0141 552 0126 or email c.thomson@dd-int.com.
Issued by Michael Crawford at Blueprint Media, 0141 353 1515.
