PATIENT-CENTRIC SOLID DOSAGE FORMS

o The Three Pillars of Patient-Centric Strategy:

1. Input and Understanding: Utilize patients’ input to get a better sense

of their needs, so we can design and deliver solutions that help fulfill
them
2. Solutions and Outcomes: Engage and support patients and other
stakeholders, ensuring the solutions that we deliver enhance their
lives and improve outcomes
3. Culture and Community: Involve and support our employees to
create an engaged community and patient-centric culture

“Legal, compliance, and regulatory issues are good excuses to stick with the status quo, but
we have to move past that. It is risky to be patient-centric. You also have to think about
what you’ll actually be able to do with patient feedback because if you talk to patients and
they give you feedback and you don’t act on it, they are going to know.”—Life sciences
executive
When patients are engaged from the beginning of a product’s development, the long-term
advantages for all parties cannot be understated. PCDD can improve the patient experience
and lead to increased adherence by enabling positive changes in many areas:
Patient Experience

o Capacity of the patient: What is the average age of your patient population? At what
stage of therapy will your treatment be administered? How will such demographics
affect the patient’s ability to comply with a product’s regimen?

o Dosage timing: Many oncology patients experience “brain fog” and therefore
struggle to keep track of dosage amounts and timing. Can regimens be simplified to
improve adherence and reduce the chances of medication errors?

o Delivery method: Both IV and oral delivery have benefits and drawbacks, so which is
right for your product? Is there a way to make combination pill and IV therapies less
confusing for the patient? Is a too-large pill getting in the way of patient compliance?

o Day-to-day disruption: When a patient must spend three weeks travelling to a

treatment center each day and then sitting in a chair for eight hours, it naturally
disrupts that patient’s life and livelihood. How can such onerous interruptions be
mitigated?

o Side effects: Side effects from oncology treatments are notoriously grim. Can these
be mitigated or better managed by getting early-development patient input?

o How can a patient centered medicine help manage a disease?

o How does patient-centered care help in the treatment of a disease?

The primary goal and benefit of patient-centered care is to improve individual health
outcomes, not just population health outcomes, although population outcomes may also
improve.

However, creative formulation approaches that can be used to enable patient-centered

solutions do not always relate to product stability. For example, Halozyme Therapeutics has
been successful in applying its proprietary Enhance technology for subcutaneous delivery of
large injection volumes to enable convenient delivery of high-dose products that otherwise
would have to be delivered intravenously. Another company with creative technology for
improving patient convenience is Alkermes. Using controlled-release and long-acting
technologies, the company is improving product concepts that reduce the frequency of
administration, leading to increased patient compliance. The patient-focused approach to
product development may be a relatively new concept, but it is certain to remain a key
aspect of drug development in the future. As an increasing number of novel product formats
emerge — such as complex protein constructs, mRNA drugs, viral vectors, and products
based on mixing two or more active ingredients — challenges are likely to increase in
addressing their required quality attributes for patient-centered product formats.

Patient-centricity can inform clinical trial design and assist with patient recruitment and
retention thereby driving the development and delivery of new, high-value health
innovations.
 o Some of the examples, where patient-centered treatment is implemented.

1. Patient-centered cancer treatment.

A primary goal of patient-centered treatment planning is to engage patients and
their families in meaningful, thorough interactions with their health care providers to
develop an accurate, well-conceived treatment plan, using all available medical
information appropriately while also considering the medical, social, and cultural
needs and desires of the patient and the family. Some of the features of patient-
centered care raised at the workshop include the importance of patient education
and empowerment; communication that involves patients, family, and friends,
explaining treatment options, and including patients in treatment decisions that
reflect patients' values, preferences, and needs; coordination and integration of
care; and the provision of emotional support as needed to relieve fear and anxiety
and address mental health issues.
A number of model programs have attempted to make cancer treatment planning
and other aspects of health care more patient-centered. These models include
patient coaching programs, centers for shared decision-making, enhanced discharge
programs, accountable care systems, and self-help support groups. For example, the
University of California, San Francisco's Carol Franc Buck Breast Care Center has a
Decision Services program that offers decision aids and informational packets in
advance of patient visits, planning calls to assist patients in developing questions for
their providers, and note-takers to accompany patients to their medical
appointments.

Each patient with cancer can be compared to a fingerprint each one is unique. The
type of cancer, the age of the patient, his or her weight, and several such factors determine
the kind of treatment plan to be offered and the resulting outcomes. A treatment plan may
entail a prognostic and therapeutic plan at the time of initial diagnosis, which can be
updated with changes during the course of treatment, as well as a prognostic and palliative
care plan near the end of life. Patient-centered care is argued to be an essential component
in the delivery of quality health and cancer care. This manuscript discusses the need to
generate credible data which indicates the quality of patient-centered care provided by
cancer treatment centers. Patient-centered care covers six domains including physical
comfort; emotional support; respect for patients’ preferences and values; integration and
coordination; involvement of family and friends; and the provision of information,
communication, and education to enable patients to understand and make informed
decisions about their care.
 2. Patient-centered treatment for Parkinson’s Disease.

Patient-Centered Care Living well with Parkinson’s disease (PD) begins by taking a patient-
centered approach to healthcare. People experience Parkinson’s differently. By building a
diverse team of health experts to successfully manage your unique PD symptoms, you can
maximize your quality of life. Although there are general guidelines that doctors use to
choose a treatment regimen, each person with Parkinson’s disease (PD) must be individually
evaluated to determine which drug or combination of medications is best for them.

Parkinson's disease (PD) is a chronic neurodegenerative disease with complex motor and
non-motor symptoms often leading to significant caregiver burden. An integrated,
multidisciplinary care setup involving different healthcare professionals is the mainstay in
 the holistic management of PD. Many challenges in delivering multidisciplinary team (MDT)
care exist, such as insufficient expertise among different healthcare professionals, and poor
interdisciplinary collaboration, and communication.

Carbidopa/levodopa immediate release (brand name Sinemet) is the original formulation

and the one that is most frequently used. This is typically the first formulation to be tried
when someone is started on levodopa treatment. This medication comes in three dosages
10/100, 25/100, and 25/250.

Parkinson’s disease (PD) presents varying motor and non-motor features in each patient
owing to their different backgrounds, such as age, gender, genetics, and environmental
factors. Furthermore, in the advanced stages, troublesome symptoms vary between patients
due to the motor and non-motor complications. The treatment of PD has made great
progress over recent decades and has directly contributed to an improvement in patients’
quality of life, especially through the progression of advanced treatment. Deep brain
stimulation, radiofrequency, MR–guided focused ultrasound, gamma knife, levodopa-
carbidopa intestinal gel, and apomorphine are now used in the clinical setting for this disease.
With multiple treatment options currently available for all stages of PD, we here discuss the
most recent options for advanced treatment, including cell therapy in advanced PD, from the
perspective of personalized medicine.
 Before selecting medications for type 2 diabetes and to promote optimal outcomes,
three factors should be evaluated: patient-specific, metabolic/physiologic-specific, and
medication-specific.
 Type 2 diabetes medication selection should be individualized with a focus on
cardiovascular risk reduction and avoidance of hypoglycemia.
 Nurses are essential in educating patients about type 2 diabetes management, including
medication options and medication-taking behavior.

Consider potential side effects when selecting a medication class and discuss them with
patients. For example, if a patient has a pre-existing diagnosis of chronic urinary tract
infections (UTIs), an SGLT-2 inhibitor may not be the best option as this class can lead to an
increase in UTIs. If a patient has uncontrolled GI conditions, such as irritable or
inflammatory bowel syndromes, a GLP-1RA or metformin would not be ideal because they
can cause GI side effects such as diarrhea, constipation, and bloating and may exacerbate
underlying symptoms. A one-size-fits-all medical management approach for type 2 diabetes
doesn’t exist. Nurses, in collaboration with the rest of the patient’s care team, should
consider individual factors when selecting medications. When possible, encourage patient
choice and input and choose medications proven to reduce cardiovascular risk. Clinical trials
have suggested that when shared decision-making is applied to clinic visits, patients
increase their knowledge, experience improved communication with healthcare providers,
have more realistic expectations about treatment outcomes, and feel a sense of increased
autonomy.

Introducing “Pharmionics” to enhance Patient-Centric Drug Development

Researchers and leading companies in the supply chain are doing their part to advance the
science of drug adherence. According to the 2012 Ascertaining Barriers to Compliance (ABC)
paper “A new taxonomy for describing and defining adherence to medications,” there was
little agreement on a common vocabulary — necessary to accurately study the
issue.2 Searching popular life-science databases, the group studied 40 years of literature to
identify all the different terms used to describe medication- taking behavior and outline the
evolution of the lexicon associated with the field. As a result, ABC proposed the term
pharmionics, which labels and describes the study of dose adherence behavior. An
understanding of pharmionics is expected to help the industry more accurately predict and
mitigate the consequences of correct versus incorrect dosing and the harmful effects of
specific adherence errors in patient populations.

Measuring the elements of adherence (initiation, implementation and discontinuation) and

understanding the consequences of correct versus incorrect dosing followed by quantitative
analysis helps drug developers to design a product that will deliver health outcomes closer
to those predicted from the clinical trials. Failure to do this can be commercially disastrous.
In the US, more than 50% of prescribed medicines are taken incorrectly or not at all, which
can reduce the efficacy of the treatment, cause severe negative health effects and
ultimately, the failure of the drug in the marketplace.

Catalent has a broad range of experience and expertise in product development, which
sees the company support the development and launch of around 200 new products every
year.
 By adapting for each molecule’s unique characteristics and challenges, Catalent uses its
formulation and development experience, and a wide range of technologies to create dose
forms that can benefit drug developers, and help to improve convenience and patient
compliance, reducing patients’ pill burden. These dose forms include:

R.P. Scherer Softgel Solutions providing optimal drug release profiles through targeted
delivery, modified release, coated and fixed dose combinations. Innovations
including OptiGel® Bio allow oral delivery of macromolecules,
while OptiGel® Micro technology produces smaller, spherical capsules.

 OptiShell® Soft Capsules offer formulators the option of higher fill temperatures.

As the inventor of the rotary die encapsulation process still used today in modern softgel
manufacturing, Catalent continues to lead the industry with cutting-edge drug delivery
innovations. Our award-winning OptiShell® technology platform further advances drug
delivery in softgel by providing development solutions for challenging compounds contained
within complex fill formulations.
OptiShell® capsules utilize a patented shell derived from plant polysaccharides that are
ideally suited for the encapsulation of higher melting point fill formulations. Softgels
containing semi-solid matrices for modified release of poorly soluble and/or poorly
permeable drug compounds are now an option, and only Catalent has succeeded in
achieving FDA approval for such a formulation. For immediate release applications,
OptiShell® technology expands the range of compatible fill formulations and excipients
available for developing lipid-based capsule formulations, providing more solutions for
solving unique drug delivery challenges.
The combined strength of OptiShell® technology and Catalent RP Scherer Softgels enable
encapsulation of a broader range of lipid-based formulations .
CATALENT BENEFITS
 Improves bioavailability for a greater number of poorly water-soluble and poorly
permeable compounds
 Modified or extended release of compounds delivered in consumer preferred softgels
 Solves complex development and formulation challenges beyond conventional softgel
technology
 Patented shell composition can handle:
 Encapsulation of high temperature fill formulations (up to 70˚C) for semi-solid and
highly viscous fill formulations
 Higher pH fill formulations
 A wider range of compatible fill excipients for enhancing drug bioavailability and
stability.
 Zydis® Orally Disintegrating Tablets- a unique, freeze-dried oral solid dosage form
that disperses almost instantly in the mouth. The new Zydis® Ultra technology provides
effective taste masking and increased drug loading for a wider range of active
ingredients.

 FlexDoseSM technology for the development of easy-to-take doses in stick packs.

In a 2013 survey on patient-centricity by research firm Patient-View, for example, ViiV

Healthcare (the GSK & Pfizer joint venture focussed on HIV therapies), Gilead, AbbVie,
Menarini and Janssen occupied the top 5 spots. Fast forward to 2016 and a review of
the eyeforpharma Barcelona Awards 2016 shows not a single one of these companies won
in the “Most Valuable Patient Initiative or Service” category, arguably the award most
focussed on patient-centricity. Instead, Sanofi took the top spot, and Merck, Roche,
Novartis and TEVA were the remaining nominees. UCB, with its renewed focus on the
patient, did particularly well that year with 3 nominations and 1 award across categories.
I would argue that this change over time is very good news for patients. It shows a degree
of competition across pharma companies and a dynamic environment aiming to improve
the status quo.
It is noteworthy that even generic pharma companies are focusing more on the patient.
The behemoth of the category, TEVA, has a number of initiatives in this space, and the
CEO of Dr. Reddy’s Laboratories, India’s largest maker of generic
pharmaceuticals, recently shared in an interview that all innovation at his company has to
be patient focussed.

References:

https://www2.deloitte.com/us/en/insights/industry/life-sciences/patient-centricity.html

https://www.ncbi.nlm.nih.gov/books/NBK202146/

https://bioprocessintl.com/manufacturing/formulation/creative-formulation-a-useful-
approach-to-patient-centered-drug-development/

https://www.ondrugdelivery.com/wp-content/uploads/2018/10/ONdrugDel-Prefilled-SI-
Devices-91-Oct-2018-PCI.pdf

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3248780/

https://www.nature.com/articles/s41591-022-01775-6

https://premierconsulting.com/resources/blog/patient-centered-drug-development-for-
oncology-products/

https://nap.nationalacademies.org/read/13155/chapter/2

https://www.mdpi.com/1183986

https://www.myamericannurse.com/patient-centered-medication-selection-for-type-2-
diabetes/
https://www.pharmtech.com/view/patient-centric-dose-forms