Drugs on Demand - 3D Printed Pills and the Future of Drug Delivery

3DP (three-dimensional printing) technology is not new in the field of medicine, as it has been used since the mid-1990s to form anatomical models for bony reconstructive surgery planning. Since then, 3D printing has changed medicine in many areas with new prosthetics, implants and even 3D printed tissues and cells. Now, research is being conducted in the area of drug delivery to see if 3D printing can revolutionize how medication is manufactured and delivered.

The first instance of 3D printed medication occurred in 2015, when the Food and Drug Administration provided their first approval of a 3DP drug, Spritam (levetiracetam), indicated for seizure treatment in adults and children with epilepsy. The company behind Spirtam, Aprecia Pharmaceutical Company, is certain that they are the first company to use this technology to manufacture an already approved drug for commercial sale, through their use of ZipDose 3DP. ZipDose technology was originally developed at MIT and consisted of tablet assembly using layers of powders and printed droplets, leading to the binding of the tablet material at the microscopic level¹. This technology is now the sole proprietorship of Aprecia Pharmaceutical Company.

ZipDose – 3D printed tablets
Features	Result
Highly porous, rapid disintegration	Orodispersable tablets that can melt on the tongue in seconds
High dose loading (up to 1000 mg of drug)	Avoids dosing with multiple tablets/pills

The clinical advantages of using a 3D printed tablet is improved adherence and compliance. As commented by the CEO of Aprecia, Don Wetherhold, “By combining [3DP] technology with a highly-prescribed epilepsy treatment, Spritam is designed to fill a need for patients who struggle with their current medication experience.”¹

This technology can help improve medication adherence and its associated complications. Just under 140 000 Canadians live with epilepsy and 30 000 within this group are children². Many patients, particularly children and older adults, have trouble swallowing pill due to size, and being adherent to taking a number of doses throughout the day. In one study, about 71% of patients reported that they have forgotten, missed, or skipped a dose of their epilepsy treatment, and of the same study, half of the surveyed patients experienced a seizure event after one missed dose¹.

Alongside improving adherence, 3D printed medication allows for customization of drug doses, which will greatly help with dosing of medications for pediatric patients. “This technology could revolutionise the way we look at children’s medicines, both in terms of what they take and the ability to keep changing the dose as they grow,” says Steve Tomlin, consultant pharmacist at Evelina London Children’s Hospital, UK¹. Whereas adult patient dosing is not largely based on weight, the reverse is true for pediatric patients, and liquid medications are used to ensure correct weight based dosing for each child. However, studies have shown that even younger children prefer to take tablets, so the ability to customize the dose of each 3D printed pill will be greatly welcomed.

ZipDose technology is just the beginning of what 3D printed medication can do to optimize drug delivery. Many patients require variable dosages of their medications, so allowing the consumer or pharmacist to adjust dosages easily could reduce visits to the physician. 3D printed’s ability to form drugs in novel shapes will also allow for greater control over the kinetics of drug release; this leads to better control over whether a medication is fast acting or released gradually over the time³.

The approval of Spritam by the FDA demonstrates the willingness of industry and regulators to seriously consider the viability of 3D printed drugs. Spritam has hit the market in the spring of 2016, and Aprecia is planning on introducing multiple new products using the ZipDose technology in upcoming years. Clearly, the potential for 3D printed in pharmaceuticals will soon be determined.

Further Reading:

https://www.aprecia.com/

https://www.wired.co.uk/article/3d-printed-personalised-pill

References: 

1. Aprecia Pharmaceuticals. (2015). FDA approves the first 3D printed drug product [Press release]. Retrieved from https://www.aprecia.com/pdf/2015_08_03_ Spritam_FDA_Approval_Press_Release.pdf
2. Prasad AN, Burneo JG, Corbett B. Epilepsy, comorbid conditions in Canadian children: analysis of cross-sectional data from cycle 3 of the National Longitudinal Study of Children and Youth. Seizure. 2014;23(10):869-73.
3. Sanderson K. 3D printing: the future of manufacturing medicine. Pharm J. 2015;294(7865):598-600.

No More Achy Breaky Bones: How Pharmacists Can Step Up to Help Patients with Osteoarthritis

This is my last week at mdBriefCase Inc. which means that I have completed one more placement, and I am all the much closer to entering the workforce as a pharmacist. Looking forward, I feel that students about to enter the profession, myself included, will have a significant influence on the way pharmacy is practiced in the future, and on the way in which services are delivered. Ideally, the incoming generation of pharmacists will shape the future of pharmacy so that it is less driven by traditional dispensing functions, and more focused on the clinical services that a pharmacist can provide. However, to reach this lofty goal, I feel that relying on the knowledge I've gained during my pharmacy school lectures is not enough. Instead, I find myself turning to continuing education (CE) programs so that I can remain up to date on the newest models for care delivery, and what pharmacists can do to better serve their patients. 

With this in mind, I wanted to focus my last blog post on the condition of osteoarthritis and a corresponding CE program that prompted my reflection on how we can optimize the clinical services pharmacists provide. 

Background on osteoarthritis
Osteoarthritis (OA) is the most common form of arthritis¹. This condition affects 1 in 8 Canadians and will continue to become more prevalent as Canada’s population ages. The increase in prevalence doesn't just affect individuals with osteoarthritis - it affects the entire healthcare system as costs associated with osteoarthritis care are projected to almost triple from 2.6 billion to 7.6 billion in 2031¹.

Although osteoarthritis has historically been attributed to unavoidable and repetitive wear and tear at the joint, and therefore an inevitable part of ageing, current research suggests osteoarthritis is NOT a normal part of ageing but rather a systemic disorder from an imbalance between join destruction and repair¹. 

Pharmacist’s role in osteoarthritis care
The current healthcare system is not designed to meet the population’s growing need for preventive and chronic care - two types of care that people with osteoarthritis would benefit. One possible solution to address the gap is to mobilize pharmacists to be more involved in the care of patients with osteoarthritis. 

Pharmacists are frontline, accessible healthcare professionals, who on average see patients 5 times more frequently than family physicians¹. Pharmacists are ideally placed to screen for osteoarthritis and make recommendations, as patients with developing osteoarthritis may be seeking over the counter medications to treat their arthritic pain. Pharmacists can serve to identify patients with osteoarthritis who have not been formally diagnosed, and pharmacists can also help signpost patients to the most appropriate healthcare provider whether it be a physician, a physiotherapist, or an occupational therapist.


Advancing Practice Program: Arthritis & the Community Pharmacist
The importance of treating patients with osteoarthritis and the ways pharmacists can provide nonpharmacological recommendations for patients with osteoarthritis are but two of many topics discussed in a CE program on Advancing Practice, Arthritis and the Community Pharmacist. What the program made me realize is that I can step out of the boundaries of talking about just pharmaceuticals and that I can also help guide patients to utilize other modalities (e.g. braces and walking canes) to help with pain symptoms. The program also emphasized the importance of interconnected health teams so that other allied health professionals (such as occupational therapists, and physiotherapists) are also part of the interdisciplinary care.

In recent years, there has been a push for pharmacists to take on a bigger role in healthcare delivery for patients with osteoarthritis, which can benefit not only patients but also the healthcare system. Ultimately, the program introduced the idea that pharmacists possess untapped capabilities which -when used to the fullest through screening, signposting to other professions, and patient education- can improve outcomes for patients with osteoarthritis.

Resources

• Arthritis Society
• Advancing Practice: Arthritis and the Community Pharmacist 

References

1. Kelly J, Davis EM, Marra C. Practice guidelines for pharmacists: The management of osteoarthritis. Can Pharm J (Ott). 2017;150(3):156-168.
2. Marra CA, Cibere J, Tsuyuki RT, et al. Improving osteoarthritis detection in the community: pharmacist identification of new, diagnostically confirmed osteoarthritis. Arthritis Rheum. 2007;57(7):1238-44.
3. Marra CA, Cibere J, Grubisic M, et al. Pharmacist-initiated intervention trial in osteoarthritis: a multidisciplinary intervention for knee osteoarthritis. Arthritis Care Res (Hoboken). 2012;64(12):1837-45.

Mary Jane and Breast Milk, a Safe Combo?

The legalization of marijuana occurred late last year and, once the excitement has died down, there remains a lot of consideration that need to be

addressed about recreational use of marijuana and its effects on different population groups.

To begin, the safety behind marijuana is murky at best. Many studies suggest that exposure to the psychoactive component of marijuana (THC) in adolescents (who have developing brains) may lead to or uncover incidents of psychoses, and in some circumstances, uncover underlying diseases like schizophrenia. However, other studies are investigating its use as a potentially safer alternative for pain management, an attractive therapy option considering the current opioid crisis arising from opioid overuse. Amidst the sparse data that is currently present (in a soon to be or already exploding field of research), one issue that still requires more conclusive answers is the effect of THC on infants or breastfeeding mothers.

As part of my rotation at the Center for Mental Health and Addiction, marijuana came up quite frequently as a topic of discussion. What effects did it have on the baby still in the womb who were exposed? If there were no immediate effects, would there be any long-term neurodevelopmental impacts on the babies who were exposed? One case that was mentioned to me in passing involved a parent who was unsure if they can smoke cannabis as a sleeping aid, while breastfeeding their baby in the evening time.  I imagine that the patient’s clinician did not have an easy time providing an answer.

From a pharmacological perspective, it is known that breastfeeding infants will be exposed to marijuana used by the nursing parent (regardless of how the parent takes in the substance, from eating edibles to vaping). The chemicals found in marijuana like THC and CBD are considered lipophilic molecules, which means they are easily taken up by and stored in adipose tissue and cells and would most likely pass easily from the mother to the milk. Once taken up by the infant, the molecules will be stored in lipid-rich tissues like the brain. These molecules tend to stay in the body for long periods of time, and even longer if the person tends to use marijuana on a regular basis, taking at least 30 days for the chemicals to completely clear the mother’s system. A recent study done by Bertrand et al. in 2018¹ also found that THC, the most psychoactive component of marijuana (and thus potentially the most damaging) was measurable abundantly in breast milk for at least 6 days after marijuana use.

From a clinical perspective, historically, there used to exist little conclusive evidence that marijuana ingestion by babies through breast milk causes harm, largely due to the lack of studies done in the area. To date, there is no conclusive data that adequately addresses the effects of marijuana exposure on long-term neurodevelopment. However, there is an emerging trend of immediate and negative effects on both parents and infant associated with marijuana use during breastfeeding. A study by Astley and Little² suggested that exposure to THC through breastmilk in the first month of life could result in decreased motor development at 1 years old. In terms of the immediate effects of marijuana exposure through breastmilk, lethargy, less frequent feeding, and shorter feeding times have been observed.³

At the same time, a mother’s breast milk is one of the most effective sources of nutrition of a growing infant, and a fed infant will fare better than an unfed infant.  Breast milk is one of the best foods for babies as it is packaged with all that a baby may need, from carbohydrates, proteins, fats, minerals, vitamins, and hormones, to maternal antibodies. Psychologically, breastfeeding facilitates bonding between mother and infant. While it would benefit the parent to err on the side of caution and cease any marijuana use until the baby grows up to no longer require breastfeeding, parents who cannot stop marijuana use may be helped through a harm reduction approach of lowering dose and frequency as much possible while continuing to breastfeed. The risks and benefits of marijuana use during breastfeeding should be provided for breastfeeding mothers to address any misconceptions about marijuana use, and close support should be offered for both parent and the developing infant.

Undoubtedly, the question of marijuana's safety in adults, in pregnant mothers and every demographic in between is something every healthcare provider needs to review. As the use of marijuana becomes more and more accepted here in Canada, more and more patients and parents will be curious about very same things, and healthcare providers will need to help them navigate through these murky waters, hopefully giving them sound, evidence-based information to make an informed decision.

Resources

https://ocs.ca/blogs/facts-about-cannabis-consumption

Canada’s Lower Risk Cannabis Use Guidelines

SOGC’s statement on cannabis use

References

1. Bertrand KA, Hanan NJ, Honerkamp-smith G, Best BM, Chambers CD. Marijuana Use by Breastfeeding Mothers and Cannabinoid Concentrations in Breast Milk. Pediatrics. 2018;142(3)
2. Astley S, Little RE. Maternal marijuana use during lactation and infant development at one year. Neurotoxicol Teratol 1990;12:161-8.
3. Committee on Nutritional Status During Pregnancy and Lactation, Institute of Medicine. Illegal drugs. Washington, DC: National Academy Press; 199

#Lets Keep Talking - How Pharmacists can be Mental Health Champions

On January 30th, Bell Media held its annual #Let’s Talk event, an initiative meant to move mental health forward in Canada by fighting stigma, improving access to care, supporting research and promoting positive workplace mental health. While this year’s event has ended, I wish to continue the conversation and discuss how pharmacy professionals can work towards providing optimal mental health care. 

Quick Facts on mental illness and addiction in Canada:^1,2,3

In any given year, 1 in 5 people in Canada will personally experience a mental health problem or illness.

• Mental and physical health are linked. People with a long-term medical condition such as chronic pain are much more likely to also experience mood disorders. Conversely, people with a mood disorder are at a much higher risk of developing a long-term medical condition.
• The disease burden of mental illness and addiction in Ontario is 1.5 times higher than all cancers put together and more than 7 times that of all infectious diseases. This includes years lived with less than full function and years lost to early death.

Being one of the most accessible health care providers, those in the pharmacy profession -pharmacists, technicians, and students - are well situated to address the key concerns that are faced by individuals who experience mental illnesses and addiction. Pharmacy professionals can improve patient care and reduce the stigmatization of those living with mental health illnesses through simple changes that can be seamlessly incorporated into everyday practice.

1) Use people-first language:

Firstly, what is people-first language? The definition can be derived from the term itself, people-first language refers to the individual first and the condition second. The concept behind utilizing people-first language is that the mental or physical health condition is only one aspect of a person’s life and not the defining characteristic. Although it may be at first awkward rephrasing to include people-first language, use of such syntax is important. Not only does it challenge the existing tendencies of the public to view and treat individuals with mental health illnesses in dehumanizing ways, but it also helps individuals with mental illnesses feel respected as human beings rather than labelled as “abnormal” or “dysfunctional”.⁴

For example:

Use “s/he has a diagnosis of schizophrenia” or “s/he has schizophrenia” rather than saying “s/he is schizophrenic”.

When referring to individuals who are diagnosed with substance use disorders, use terms like “s/he has an alcohol use disorder”, in place of “s/he is an alcoholic” and avoid the terms “abuser” or “abuse”. It has been shown that these terms can evoke automatic negative thoughts about individuals with substance-related problems.⁵ By using more neutral terms to lessen stigma surrounding alcohol and other drug use disorders, individuals with these conditions may be more likely to seek help, stay in treatment, and achieve long-term remission.

2) Promote community supports and resources:

 Community pharmacists may the most visible part of the healthcare system and an accessible source of local information. Pharmacy professionals are valuable not only for their expertise but also for directing people to other healthcare providers or services and programs. They can leverage their skills in engaging patients, and their position as one of the most trusted healthcare professionals to provide appropriate signposting for members of the community who may benefit from local mental health and wellness services and resources.

Having information on local mental health and wellness services displayed in a prominent place can be a simple way for pharmacists and pharmacy technicians to promote access to mental health services. To best address the specific needs of the community, it may be beneficial to incorporate healthcare services that are specifically designed for a particular population subgroup; for example, community pharmacies located near university/college campuses may wish to incorporate information on campus resources available for students.

A good starting step towards building the list of resources may be to visit the website for the local Canadian Mental Health Association branch.

Of course, individual efforts are only the starting point to change the landscape of mental health support in Canada, and as a professional body, we can advocate for the development and implementation of pharmacist-delivered interventions in mental health care. In the face of growing demand and continued pressure on mental health services, it is crucial to mobilize the pharmacy professional body to address and lessen the gaps in mental health and addictions systems across the country.

References:

1. Mental Health Commission of Canada. http://www.mentalhealthcommission.ca/English/system/files/private/document/Investing_in_Mental_Health_FINAL_Version_ENG.pdf. Accessed 09/07/2015.
2. Ratnasingham et al. (2012). Opening eyes, opening minds: The Ontario burden of mental illness and addictions. An Institute for Clinical Evaluative Sciences / Public Health Ontario report. Toronto: ICES.
3. Patten et al. (2005). Long-term medical conditions and major depression: strength of association for specific conditions in the general population.Canadian Journal of Psychiatry, 50: 195-202.
4. Jensen ME, Pease EA, Lambert K, Hickman DR, Robinson O, McCoy KT, Barut JK, Musker KM, Olive D, Noll C, Ramirez J. Championing person-first language: a call to psychiatric mental health nurses. Journal of the American Psychiatric Nurses Association. 2013 May;19(3):146-51.
5. Kelly JF, Dow SJ, Westerhoff C. Does our choice of substance-related terms influence perceptions of treatment need? An empirical investigation with two commonly used terms. Journal of Drug Issues. 2010 Oct;40(4):805-18.