Lack of sleep and its effect on health

Studies show that insufficient sleep decreases attention, concentration and memory.  . In addition, lack of sleep also worsens performance and can even be a first symptom of anxiety and depression.

Sleep is a fundamental element for physical and mental health. But it is not enough to comply with a certain number of hours of sleep, it is also necessary to ensure its quality. Studies have shown that when the brain is deprived of sleep for a prolonged period of time, cognitive, memory and mood management problems are generated.

Mild cases of insomnia are commonly treated through natural means or sleep therapies. Acute cases, on the other hand, most of the time generate other problems such as anxiety and therefore require pharmaceutical assistance.

Among the safest prescription drugs to treat insomnia problems are benzodiazepines, which are hypnotic drugs with anxiolytic, muscle-relaxant, anticonvulsant, hypnotic and anesthetic properties. Popular drugs such as clonazepam, diazepam and lorazepam are found under this name.

Although well used, pain relieving drugs are very useful, they should always be prescribed and monitored by a health professional, since a bad consumption or an inadequate mixture of drugs can generate health problems and/or substance abuse disorder.

The boom in antidepressants

According to a study conducted by the Observatory of Addictions and Problematic Consumption, due to the Covid-19 pandemic, in Argentina alone, the consumption of psychotropic drugs grew 4 times more than the average of drugs in general. Of these, clonazepam and alprazolam, which are sold by prescription, were among the most sold drugs.

In other countries such as Spain, the consumption of anxiolytics and antidepressants grew by around 6% in the last year, equivalent to 54 million boxes of anxiolytics and 45 million antidepressants prescribed.

The increase in the consumption of these products was also supported by the inclusion of mental health problems in the public health plans of different countries, especially developed countries.

Melatonin as an alternative to drugs

Melatonin is a hormone that is naturally produced in the brain when it is exposed to darkness, allowing the brain to transition between being awake and asleep; in other words, it is responsible for regulating sleep cycles.Melatonin is popular because it does not create dependence and has a very low risk of generating sleep inertia (waking up groggy or hungover). However, this does not mean that it is free of side problems if abused. Headache, nausea, dizziness and daytime fatigue are some of the adverse effects of its abuse.

A great opportunity for the pharmaceutical industry

As sleep problems and anxiety become increasingly prevalent and treatable in the world, it is imperative that the pharmaceutical and nutraceutical industries adapt to the new needs of consumers and health systems.

The most common format for drugs such as benzodiazepines and clonazepam is the tablet. However, over time, manufacturers have sought to develop their products in more patient-friendly and convenient formats and have explored suspensions and liquid-filled capsules. 

On this point, LFHC (liquid-filled hard capsules) technology has several advantages, both for the patient and the manufacturer. 

Advantages for the patient:

• Liquid formulations are more bioavailable than any other format and are therefore more easily absorbed by the body.
• Hard capsules can be of animal (gelatin) or vegetable origin and can therefore be adapted to different market segments, such as the vegetarian market.
• Liquid-filled hard capsules allow high customization, both in color and printing, so manufacturers can differentiate their products in a way that makes them easier for patients to identify. This is not achieved with any other format.

Advantages for the manufacturer

• When encapsulating liquids in hard capsules, it is not necessary to formulate the capsule structure, as is the case with soft capsules. This simplifies the encapsulation process and reduces costs and production times.
• This also makes the process of encapsulation of liquids in hard capsules possible in the manufacturer’s own facilities, without having to outsource the process or hand over the recipe of the formula to an outsider. 
• High potency drugs, such as some of the common tranquilizers, perform better in liquid formulations, as they require fewer excipients and are more homogeneous in this medium. 

In addition, they involve less risk for the manufacturer’s operators, as they require fewer steps in the mixing of ingredients and generate less risk of toxicity in the air.

Antidepressants and tranquilizers in liquid formulation

Currently, several products to treat insomnia and anxiety are available on the market in liquid formulas; an example of these is clonazepam.Melatonin, on the other hand, is more commonly found in gummies or softgels, but this does not mean that it cannot be formulated in hard capsules. In fact, the development of melatonin in liquid capsule form represents a great opportunity for manufacturers, because of all the advantages mentioned in the previous paragraph.

In conclusion

Sleeping well is essential for health, as a poor routine can generate health problems that can lead to more serious diseases such as anxiety or depression. Despite the fact that the pandemic has increased mental health and sleep problems in the world, different governments and public institutions are developing programs and treatments to counteract this trend.

For this reason, it is the task of the pharmaceutical and nutraceutical industry to develop products for insomnia and anxiety that adapt to the new needs and lifestyles of patients, being the format of hard capsules filled with liquid one of the most recommended.

References

 ¹El consumo de psicofármacos aumentó 4 veces más que los medicamentos en general debido a la pandemia – DiarioAr https://www.eldiarioar.com/sociedad/coronavirus/consumo-psicofarmacos-aumento-4-veces-medicamentos-general-debido-pandemia_1_8369644.html

²Melatonin. Mayo Clinic https://www.mayoclinic.org/drugs-supplements-melatonin/art-20363071

³Melatonina por forma: ventajas y desventajas de las píldoras, las gomitas y los líquidos – EVERYDAY HEALTH https://www.everydayhealth.com/melatonin/pros-cons-pills-gummies-liquids/

⁴Cómo afecta la falta de sueño a nuestro cerebro – Clinica NYR https://clinicanyr.com/como-afecta-la-falta-de-sueno-a-nuestro-cerebro/#:~:text=Dormir%20pocas%20horas%20afecta%20adem%C3%A1s,en%20esta%20%C3%A1rea%20del%20

Although some sectors have managed to improve their product supply and shipping logistics over the months, recent international and health circumstances have caused shortages to intensify again.

Unfavorable circumstances

Some of the scarcest materials in 2022 that can affect the production of finished pharmaceutical products are active pharmaceutical ingredients or APIs. The main reason for this is that Approximately 80% of all APIs produced in the world come from India and China. 

This has been a major drawback since the beginning of the pandemic, as many pharmaceutical producers in the world depend on Asian APIs, which have been greatly affected by the lack of labor for their production or the scarcity of raw materials at a global level. 

Additionally, we have the problem of international supply and logistics disruption,  which has been going on since 2021 and is currently exacerbated by the closures of Chinese companies and cities (due to recent outbreaks of the virus), and is expected to continue well into 2023.
As if that were not enough, the other major producer of API’s in the world is the European Union, and due to the conflict between Russia and Ukraine, the production and distribution of some components in that continent has been interrupted as a result of sanctions or restrictions in those territories.

New challenges, new opportunities

As API production and supply is concentrated in certain regions of the world, it is imperative that drug manufacturers start looking for new options to overcome this reality, in the form of suppliers located in the same country or region.

It is also important to review the production processes of existing pharmaceutical products to determine whether they can be adapted or modified to make them more competitive in today’s demanding and changing market.

This is where options such as reducing or changing excipients or changing formulas arise. And although this decision is not easy to make from the production point of view, there are some ways that can make the change simpler.

Among the world’s most popular pharmaceutical formats are hard capsules, which are widely accepted because they are cost-efficient, easy to fill, and suitable for multiple needs. What few manufacturers are aware of is that, with the variation of liquid-filled hard capsules (LFHC), additional advantages are obtained that may be the solution to the current shortage of APIs. 

The liquid-filled hard capsules were originally developed to encapsulate substances that are: 

• Low melting point  
• Unstable in contact with oxygen or moisture 
• Poorly soluble in water 
• Very high potency or requiring very low doses

This last point is of great interest, since when HPAPIs or high potency active ingredients are handled, less of these components are normally used in the manufacture of the drug, due to their high potency.

Additionally, HPAPIs are ideal to be formulated in liquid media, as this format requires fewer excipients and manufacturing steps, which is ideal in the current context of scarcity of raw materials.

Even if the drug to be manufactured does not include high potency actives, LFHC technology is also ideal, as the liquid formulation is the most bioavailable formulation available, which means that it is more easily absorbed by the body and therefore the effect of the drug is felt faster. 

This, in practical terms, means that the patient may generate preference for this drug over others simply because of its rapid effect.

In conclusion

Liquid-filled hard capsules are an excellent way to circumvent the challenging circumstances of today’s pharmaceutical industry. Their advantages are not only limited to the issue of costs and raw materials, but can also generate greater consumer preference for a product in the medium and long term.

Moreover, the change in terms of production is not complex, since the same equipment used for filling hard capsules filled with dry components can be used for filling liquids, with some modifications and adjustments. 

The global reality teaches us to react quickly to change and to have several options available at all times. Therefore, the success of a drug manufacturer will depend on the quality and proximity of its suppliers, as well as the ease with which it can adapt its products to new trends, or even the fact that its own products generate them.

Because of this, collagen is known for its contribution to the proper functioning of these tissues, but also for the benefits it has for improving the elasticity and hydration of the skin, nails and hair, and for delaying the signs of aging..

Its consumption is recommended after the age of 30, when the body slows down its production, leading to wrinkles and dry skin, along with other degenerative problems of tissues and tendons. Collagen is 100% animal derived from the tissues and joints of some mammals or from fish scales. This makes it a product out of the reach of people who follow a vegan or vegetarian lifestyle. However, a vegan “collagen”, ideal for this type of people, has been marketed for some years now.

How does vegan collagen work?

The human body produces collagen to a greater extent during the first years of life and in general, when it is adequately nourished. This is the objective of the so-called vegan collagen; to enhance the natural production of collagen in the body.  Therefore, it is not a collagen as such, but a combination of enzymes, vitamins and substances that help the production of the protein.

Some of the substances that make up vegan collagen are:

• Vitamins C, A and E
• Yeast 
• Zinc
• Antioxidants
• Biotin
• Hyaluronic acid
• Fruit and vegetable extracts

Benefits of vegan collagen

Like traditional collagen, the benefits of vegan collagen are numerous; however, its effectiveness is linked to the body’s ability to absorb the ingredients responsible for stimulating collagen production, which depends on the age and metabolism of each individual.

However, the best-known benefits of vegan collagen include: 

• Increased energy.
• Improved immune system.
• Balancing of seasonal allergy symptoms.
• Improved sleep.
• Reduces anxiety.
• Protects the liver.
•  Improves scarring.

Why produce vegan collagen

Although relatively new, this product has had great acceptance among the vegetarian and vegan public, because it is a natural alternative and because it has some benefits that traditional collagen does not have, such as:

• Avoids possible allergic reactions to animal components.
• It is ideal for animal lovers, as it does not include animal ingredients.
• It is more economic to produce than traditional collagen.

On the other hand, the vegan market is one of the fastest growing and potential markets in the world. In 2018 it reached a value of $14.8 billion and is expected to reach $31.4 billion by 2026.¹Now, the specific segment of nutritional supplements made from plants reached a value of 4.2 billion in 2018 and is expected to have a growth of up to 7 billion, by 2026.²

The best format for your herbal collagen supplement

Both animal collagen and its vegan counterpart are available in a variety of presentations ranging from traditional powder for mixing, tablets, capsules, gummies and even in liquid, ready-to-drink form.

The most suitable presentation for your product depends on several factors, including its composition, target segment and production costs.

The best products are those containing Vitamin C, as this ingredient helps the body to synthesize protein naturally. Moreover, if the purpose of the collagen enhancer consumption is purely aesthetic, it is recommended to consume products that also include vitamin E, A and antioxidants. 

Whatever the composition of the product, the recommendation is to make it in a format that favors absorption, which is achieved more quickly through liquids.

The liquid presentation of vegan collagen is not the most popular, with a few brands offering the product with a dropper dispenser or in single-dose sachets. These tend to be more expensive and less common in the market.

Fortunately, there is a more affordable option for packaging your vegan collagen in liquid form and that is the liquid-filled hard capsule.

Advantages of vegan collagen liquid filled capsules

Liquid-filled hard capsules are a format that includes the best of both worlds: the convenience and economy of a hard capsule, with the benefits and efficacy of liquid formulations.  

Liquids are more bioavailable than any of their tablet or powder counterparts, which means they are more readily absorbed by the body and, consequently, pass into the blood stream faster. 

In addition, with the vegetable version of these capsules, made from HPMC or hydroxypropyl methylcellulose, the risk of altering the vegan or vegetarian diet is eliminated.

On the other hand, the liquid-filled hard capsules come in a wide variety of sizes, so that the desired dose of collagen can be adjusted according to the different nutritional needs of the individual or the target segment.

With powder, for example, there is a single dose, which must be administered to all types of patients. Therefore, if an individual requires a lower dose, he or she will have to use the single presentation partially, with the danger that the remainder may be contaminated or wasted.

Another benefit of liquid-filled hard capsules is that their production can be faster and more cost-efficient than others. With powders or tablets, for example, mixing the dry ingredients may take several steps to achieve the desired homogeneity of the product. 

With a liquid formulation, on the other hand, all the dry ingredients are mixed together with a liquid excipient in a single step. In addition, this process avoids the dispersion of the dry components, which can occur in the manufacture of tablets and generates waste.

Compared to other presentations such as soft capsules, the liquid formulation in hard capsule is also more convenient in terms of cost, since its manufacture can be done at the producer’s facilities and with the same dry encapsulation machines. While soft capsules must be made with special equipment, it is usually better to outsource the process, which implies delivering the formulation to an external supplier.

Vegan collagen is an excellent alternative to traditional collagen and is a very attractive product for the ever-growing vegan and vegetarian market. Therefore, it is interesting to analyze each of its production possibilities and possible formats, without forgetting that there are more and more competitors joining this market and that it is essential to offer a product that is not only cost-efficient and profitable, but also attractive and differential to the public.

References

 ¹Allied market Research, Vegan Food Market by Product Type (Dairy Alternative, Meat Substitute and others) and Distribution Channel (Offline and Online): Global Opportunity Analysis and Industry Forecast, 2019-2026.

²Allied market Research, Plant Based Protein Supplement Market by Nature (Organic and Conventional), by product type (Soy, Spirulina, Pumpkin Seed, Pea and others), by form (Protein Powder, Protein Bar and Ready-to-drink), by application (Sports Nutrition and Supplement Nutrition) and Distribution Channel (Hypermarket/Supermarket, Specialty Store and online Store): Global Opportunity Analysis and Industry Forecast, 2019-2026.

A bit of context

According to their function, this type of drug is divided into three types: primary, secondary and adjuvant. 

Primary analgesics have the sole function of relieving pain and are usually broad-spectrum, i.e., they relieve different types of ailments. This group includes drugs such as paracetamol, non-steroidal anti-inflammatory analgesics such as ibuprofen, and opioids such as morphine.

Secondary analgesics have additional functions and relieve specific pain. They are also narrow-spectrum. Among the most popular are diazepam, tetrazepam and lidocaine.

Adjuvants are those drugs that help primary analgesics with pain management, because they do not act sufficiently on their own. Some of these medications are antidepressants, antiepileptics and corticosteroids.

Depending on their type of sale, analgesics can be over-the-counter or prescription painkillers. 

Among the most common over-the-counter analgesics are acetaminophen and nonsteroidal anti-inflammatory drugs such as ibuprofen and aspirin. On the side of the most popular prescription painkillers, we find codeine and steroids such as cortisone.

The attractive market for analgesics

Given that pain is one of the most common health problems in the world, it stands to reason that the market for pain medications is highly attractive. In the United States alone, more than 30% of the population (by 2019) was living with some form of chronic pain². Also in that country and in the same period, one in five adults claimed to have some type of chronic pain.

Because the simplest and least expensive way to treat pain is through OTC drugs, this market represents one of the most important in the pharmaceutical sector, with the Asian market being the most important in terms of growth³. 

Globally, the OTC market is expected to grow by 6.65% for the period 2002-2027³ and within this market, the analgesics segment is expected to grow at a 5% CAGR by 2031, with an approximate value of US$40 billion.⁴

Against this backdrop, it is very attractive to enter or diversify its business into OTC analgesic products, especially in the North American region, one of the most profitable in the world, with a value of 5.6 billion dollars (2021) and an expected growth of 5.9 billion dollars by 2031⁴.

The best-selling analgesic globally is acetaminophen and it is also the second best-selling generic molecule in the world. It is known by the alternative name of acetaminophen and its most popular commercial product is Tylenol. 

Acetaminophen is a commonly used analgesic and has the advantage that it has no adverse effects on the stomach mucosa. For this reason, it is considered safe to take along with other medications and to administer to the pediatric and geriatric population.

The second best-selling analgesic globally and the fifth best-selling generic molecule in the world is ibuprofen. Its most popular product is Advil. 

This drug acts on the body by reducing its ability to produce pain-causing chemicals. In addition, as a non-steroidal anti-inflammatory it helps in reducing inflammation, which makes it ideal for ailments such as arthritis.The eighth best-selling generic molecule in the world and the third best-selling analgesic is acetylsalicylic acid, commonly known as aspirin. It is part of the non-steroidal anti-inflammatoryanalgesics (NSAIDs) and has the advantage that it is also a platelet antiaggregant, which means that it modifies blood clotting. For this reason, it is a drug recommended to treat circulatory issues and to prevent thrombosis or heart attacks.

Skills and opportunities

The outlook for the analgesic market is very promising, especially after the European Medicines Agency suggested that cases with mild Covid-19 symptoms could be treated with non-steroidal anti-inflammatory drugs such as ibuprofen and acetaminophen.

This generated a boom in the purchase of these drugs, especially those with a faster response in their effect, also known as fast-acting drugs. 

Within the fast-acting formats, syrups and suspensions are the fastest in terms of absorption, since the body needs the nutrients to be in a liquid medium in order to assimilate them properly. However, they are not the most practical dosage form, so they are usually relegated to pediatric use.

After liquids, the format with the fastest absorption speed by the body is the liquid-filled hard capsules. Because they are composed of two pieces, they disintegrate more easily in the stomach, releasing their contents quicker. 

They are also the most cost-efficient option for a fast-acting analgesic, as they are less complex to produce than other formats, such as soft capsules, and are therefore also less expensive.

Advantages of producing your analgesic in liquid capsule form

• The capsule format is the second most widely used by the pharmaceutical industry and is proven to be one of the best in terms of cost-benefit ratio. In addition, by including the analgesic formulation in a liquid medium, it favors its absorption by the bloodstream, which translates into a faster effect.

• Hard capsules are very easy to swallow and can be formulated in different sizes, which is an advantage for your product development, as it allows you to create different presentations, for different needs or types of consumers.

• In the market there is an endless number of presentation formats for analgesics, the most common being the tablet. If you want to create a differentiated product that generates greater recall for its appearance and effect, you can opt for the liquid-filled capsule, in which you can also customize the color of the capsule and the sealing band.

• The production of a liquid-filled capsule is feasible in a plant where other types of drugs or products are already encapsulated; and even with the use of the same machines. You only need to make a few adaptations and adjustments to the equipment.

• Test batches for liquid-filled hard capsules are smaller than for other formats, such as soft capsules. This is because you can test with smaller quantities of capsules and without the need to outsource the process. In the case of soft capsules, you have to use a third party for their production, which will most likely require minimum production quantities.

When choosing a dosage form for your fast-acting analgesic, remember to consider all the relevant aspects of the market, from the flexibility of the product to adapt to different needs, the practicality of administration and even the possibility of customizing it according to your brand image.

References

 ¹Bilge, S. y Gunaydin, C. Effects of Nonsteroidal Anti-Inflammatory Drugs at the Molecular Level, The Eurasian Journal of Medicine, Junio de 2018.

²Doughman, E., U.S. Painkiller Market to Reach $5.9 Billion by 2023, pharmaceuticalprocessingworld.com, mayo del 2019.

³Mordor Intelligence, OVER THE COUNTER DRUGS MARKET – GROWTH, TRENDS, COVID-19 IMPACT, AND FORECASTS (2022 – 2027).

⁴Fact. MR., Over the Counter (OTC) Analgesics Market Report, October of 2021.

According to Fortune Business Insight estimates, in 2020 the global legal cannabis market was close to $20.4 billion and is expected to reach $197.7 billion by 2028.  This growth is attributed to the trend of countries legalizing cannabis-based products, including Cannabidiol or CBD.

Today, the markets of the European Union, North America, the United Kingdom and some Latin American countries have opened their doors to CBD products and since then more and more countries are following in their footsteps.

What is CBD and what is it used for?

Cannabidiol (CBD) is a natural substance from the Cannabis sativa plant, which is neither psychoactive nor psychotropic and is used as an adjunct in the treatment of pain, inflammation, anxiety, among other illnesses.

This substance is currently approved in the U.S. as a treatment for pain and certain ailments, such as convulsions; and despite being a derivative of marijuana, it does not generate hallucinogenic effects, as do other derivatives of marihuana.

CBD acts on certain receptors in the body, as follows:

CB1

Which is found in the brain and is responsible for the production of hormones, neurotransmitters and the action of neurons.

CB2

Found in the lymphoid organs such as the spleen or bone marrow, which are responsible for generating a response to infections or inflammation in the body.

What conditions are treated with CBD products?

The use of CBD products and their commercialization differ greatly, according to the country or legislation under which they are found. However, the most common applications of the product are being directed to the following conditions and/or diseases: 

• Epilepsy
• Post-Traumatic Stress
• Insomnia
• Inflammations
• Rheumatoid Arthritis
• Skin problems such as Psoriasis

In addition, because CBD is oily in nature, it is well accepted by a wide variety of patients, who find its consumption much more pleasant than that of other supplements or treatments.

CBD product dosage forms

Currently, CBD products are marketed in two formats.

On the one hand, in liquid and bottled presentation, whose dosage must be done directly by the patient through a dropper; or in liquid-filled capsules, which can be soft or hard and have the advantage of having a dosage already included in each capsule, which avoids overdosage.

But beyond the ease of administration, liquid-filled capsules have another great advantage: because the CBD is encapsulated in a barrier, which can be of gelatin or vegetable origin, the patient does not have direct contact with the oil, which has a bitter taste, something that can be unpleasant for some people.

In addition, if the capsule is hard, there is the added benefit that the odor of the oil, similar to that of marijuana, will not be filtered; thus obtaining a capsule without taste and odor which will be the best option for any patient.

Production Advantages

Although hard capsules for liquids have existed for decades, advances in production processes in recent years have led to increased competition and lower prices for these products , which are now used in medicines of all kinds.

Although hard capsules for liquids have been around for decades, the advances in production processes in recent years that are now used in medicines of all kinds have led to the development of a new type of liquid capsule.

The following are some of its most important benefits:

Fast manufacturing

While soft capsules take two to three days from gelatin preparation to packaging, all process cycle steps for liquid-filled hard capsules are completed in one day, including banding or sealing of the capsules.

Avoid the risk of oxygen migration into the interior

Because they do not have plasticizers like their soft counterparts, the risk of oxygen leaking into the capsule is minimal, which could lead to oxidation in the formulation.

No waste of raw materials

While soft capsules have a waste of up to 40% of raw materials during production, liquid-filled capsules have minimal waste, which helps to optimize production costs.

Flexibility in production scale

Another benefit that liquid-filled hard capsules offer when working with CBD products is the ability to easily adapt to any scale of production. This is of great importance since, as a growing industry, it is difficult to estimate the batches that may be needed for long-term commercialization.

The process of encapsulation of liquids, or in this case of oil in hard capsule, can be carried out in the producer’s own facilities and with the same encapsulation machines as for dry formulations (with some special attachments). Even small test batches can be generated and their production can be adjusted according to market needs.

While the production of soft capsules is highly complex and requires expensive and specific machinery, which means that in 90% of the cases, it must be outsourced, increasing costs, development times and raw materials.

Therefore, it is considered that liquid-filled hard capsules are the best format for producers who so far are venturing into the CBD market, or any other market that requires liquid or mixed formulations, since it allows scaling up production, with the guarantee that much higher market shares can be covered in the future, without the need to change presentation or format.

Versatile technology for a growing industry

Currently, many countries around the world are seeking to update their local legislation to benefit from the new perspective with which medical science is approaching cannabis derivatives.

An example of this is the government of Colombia which, despite the difficulties in the legislative field, has already commercialization laboratories of CBD products for export for figures exceeding 8 million dollars in less than two years and which is expected to continue to grow in the coming years.

The opportunities in the CBD market are very attractive and are improving as governments ease their restrictions on CBD products. The key is to enter the market at an early stage to take advantage of new opportunities and partners that arise in each region.