Pharmaceuticals 8th December 2023     5 min read

Redefining Rest - IMCD's Innovative Approach to Melatonin

Novel pharmaceutical dosage forms require more than just a bit of creative thinking. Tasked with developing a formula that mimics the natural circadian rhythm of melatonin, our Pharmaceutical Technical Centre (PTC) Mumbai stepped in. Using a range of speciality ingredients, our technical experts created an innovative solution that challenges existing market products. 

Based on Innova Market insights, about 26% of consumers globally claim to take supplements daily.1 Mental wellbeing and brain function has been a particular focus in supplement NPD in recent times, as consumers continue to look after their mental health as well as their physical health. The importance of quality sleep on mood and mental performance has led to strong growth in Insomnia positionings, and this is an area to watch.1 In the US, insomnia makes one of the top 10 most relevant health categories 1, – a fact that highlights how important sleep health is becoming in the market.2

There are many melatonin products on the market, both immediate release and sustained release that come in various dosage forms, including tablets, capsules, and even gummies. Numerous ingredients have appeared in these categories, from both synthetic and natural origins. However, one ingredient remains synonymous with the treatment of insomnia - melatonin.

What is melatonin (MT)?

Melatonin is a hormone that regulates the sleep-wake cycle, is induced by darkness, aids sleep onset and maintenance,  and is used as a supplement for health issues. To ensure peaceful sleep without disruption, it’s essential to ensure an effective level of melatonin during the sleep process. Within healthy individuals, MT levels start to increase naturally in the evening, peak in the night, and slowly decrease in the morning, allowing us to gradually wake up. This can be explained as an almost two-phase release that naturally helps the quality of the sleep.3

Yet, many products on the market offer either an immediate release or a sustained release (after a certain period of time) for MT, both failing to imitate the natural endogenous biorhythm of MT that ensures quality of sleep. Additionally, MT has a very short half-life of 20-50 min and a low bioavailability of 15%.

Technical challenge and solutions

The PTC Mumbai team took on the challenge of creating an innovative dosage form with a pulsative release that follows the natural rhythm of the human body. They formulated a 5mg melatonin capsule that has two release peaks -one lower one, that induces sleep, and following a break, a second, more intensive one, that contributes to the quality of the sleep.

The innovative formula consists of 80% drug layering on sugar pellets, followed by enteric coating. This allows for the sustained release of this amount of MT after it passes through the stomach (after 2h - second peak) 4.

The additional 20% was placed on the top of the pellets, ensuring an immediate release (first peak). These coated pellets were placed into capsules and the release profile and stability was tested.

The result was a pulsatile dosage form that mimics the endogenous MT release, where a small fraction of melatonin (20% or 1mg) is first released to initiate sleep, and the remaining melatonin (80% or 4 mg) is subsequently released after a delayed period of 2 hours. The melatonin pulsatile release dosage form was successfully developed using both single-unit and multiple-unit pellets in capsules.

The work of the team was admitted as a poster for the prestigious AAPS PharmSci 360 (American Association of Pharmaceutical Scientists) that took place in October this year.   

Technical Expertise

At IMCD, we have a network of six dedicated Pharmaceutical technical centres across the globe to support our customers and partners at every stage of the product development cycle. Our global pharmaceutical centres deliver a range of trainings, develop projects and concepts, and tackle scientific challenges that have wide application appeal. To learn more about IMCD's pharmaceutical network and technical expertise click here.

References:

1. Innova - Global Supplements Trends
2. News in Health (2022) https://newsinhealth.nih.gov/2022/04/melatonin-supplement-use-rising-among-adults 
3. Zisapel N. (2018), New perspectives on the role of melatonin in human sleep, circadian rhythms, and their regulation, British Journal Pharmacology. Aug;175(16):3190-3199.  
4. Beatrice Albertini & et al (2014), Formulating SLMs as oral pulsatile system for potential delivery of melatonin to paediatric population, International Journal of Pharmaceutics, 469 (1), 67-79.