Parkinson’s disease (PD) is a progressive, neurological condition affecting the brain’s ability to coordinate movement. PD occurs when the brain cells that produce dopamine, a chemical messenger or neurotransmitter, become dysfunctional or die. The exact cause of PD is unknown, but research suggests that genetics and environmental factors play a role in the development of the condition.
Symptoms of PD
Symptoms of PD develop and worsen slowly over time, significantly impacting daily function and quality of life in those affected by the condition. PD symptoms are divided into those that affect movement, or motor symptoms, and those that affect things other than movement, or non-motor symptoms.
Motor symptoms include the following:
Slowed movement (bradykinesia)
Difficulty initiating movement
Difficulty walking characterized by a shuffling gait pattern and/or freezing of gait
Resting tremor, notably a pill-rolling movement of the thumb and index finger
Involuntary movements (dyskinesias)
Problems with balance that may lead to frequent falls (postural instability)
Rigidity or stiffness of the muscles
Non-motor symptoms may include the following:
Cognitive impairment
Dementia
Depression or anxiety
Changes in sensation
Pain
Sleep disturbances
Progression of PD
Over time, these symptoms can progress to the point where performing daily activities becomes increasingly difficult, particularly due to motor symptoms. Motor symptoms of PD progress over 5 stages as defined by the Hoehn and Yahr Scale in 1967.
Stages 1 and 2 indicate milder, early-stage PD symptoms, stage 3 indicates mid-stage disease, and stages 4 and 5 indicate more advanced stages of disease progression, requiring significant assistance with daily tasks.
Treatment of PD
Although there is no cure for PD, certain treatments can help to manage PD-related symptoms. These treatments may involve medications, surgeries including implantation of a deep brain stimulator, or rehabilitative therapies, such as physical therapy, occupational therapy, speech therapy, and psychotherapy.
One of the most effective medications used to treat PD is levodopa, a precursor to dopamine. Levodopa serves as a dopamine replacement strategy for people with PD and is particularly important for people who have bradykinesia that is difficult to control and is significantly interfering with daily function.
Challenges of Long-Term Levodopa Treatment
Challenges with traditional Levodopa treatment include determining the optimal dosing frequency to effectively manage symptoms while minimizing medication-related side effects, including:
Mental and behavioral changes, such as confusion, agitation, impulsiveness, hallucinations, delusions, and psychosis
Nausea/vomiting
Loss of appetite
Headache
Dizziness/lightheadedness
Drowsiness/sleepiness
Levodopa-induced side effects associated with its long-term use may include dyskinesias (excessive movements) and unpredictable motor fluctuations related to loss of medication effectiveness (on-off periods). These side effects significantly diminish quality of life, participation in activities of daily living, and emotional well-being of individuals with PD.
Consequently, motor fluctuations may require patients in more advanced stages of PD to take more frequent doses of levodopa—sometimes up to 8 times a day in a fasted state—to maintain the medication’s effectiveness. The need for more frequent doses of levodopa increases the degree of treatment burden. This treatment regimen may disrupt sleep duration or make it difficult for patients to move upon waking if they have not received a dose of levodopa during the night.
Laxxon’s Extended-Related Levodopa: A Game Changer
Laxxon Medical’s Levodopa project aims to revolutionize Parkinson's treatment by addressing the challenges of dosing frequency and improving quality of life by reducing drug intake burden for patients with PD.
Achim Schneeberger, Laxxon’s chief strategy officer (CSO), stated in an interview that Laxxon’s technology helps to “formulate the Levodopa [tablets] in a way that it releases at a certain point in time... This is achieved by a combination of having an outer surface that is retarding the release of the [active pharmaceutical ingredient (API)] and…an inner structure that has…an extended-release profile.”
This extended-release profile allows the levodopa to be released slowly over a longer period of time, particularly at night when the individual with PD is sleeping. This drug formulation strategy helps people with PD to get a good night’s sleep without having to get up in the middle of the night to take another dose of medication to prevent the medication’s beneficial therapeutic effects from wearing off. Extended release of the levodopa simultaneously enables them to be able to move in the morning when they awake.
Laxxon has created a tablet formulation using its 3-dimensional (3D) printing technology to create an extended-release profile for levodopa over a 6-hour period. This specific formulation would decrease the number of times patients with more advanced stages of PD have to take their medication throughout the day.
Improving Quality of Life for Parkinson’s Patients
Over the past 60 years, research and clinical trials have aimed to improve the quality of life for patients with PD by improving levodopa treatment once it was evident that long-term use was associated with motor fluctuations. These motor fluctuations correlated with various pharmacokinetic and pharmacodynamic properties of levodopa, including its short half-life of around 1 hour, narrow therapeutic window, problems with gastrointestinal absorption, and poor bioavailability when orally administered due to first-pass metabolism and rapid degradation and clearance by enzymes via decarboxylation to dopamine once reaching the peripheral bloodstream.
Rapid metabolism of orally administered levodopa results in approximately 1% of the active drug ingredients crossing the blood-brain barrier to reach the brain to successfully affect dopaminergic transmission. All of these factors impact the effectiveness of the medication and the patient’s responsiveness.
Co-administration of medications, such as the combination of levodopa-carbidopa, have slowed down this conversion of levodopa to dopamine in the peripheral blood via carbidopa’s inhibition of the peripheral amino acid, decarboxylase. However, this strategy has only improved the amount of active levodopa that reaches the central nervous system to 5-10%.
Research and clinical trials to improve levodopa treatment have focused on two strategies: achieving continuous dopaminergic stimulation and identifying a method of administration that instantaneously delivers levodopa to the central nervous system. These strategies aim to improve quality of life by reducing the need for frequent dosing of levodopa throughout the day as well as decreasing the unpredictable occurrences of freezing of gait, dyskinesias, on-off times, and motor fluctuations that many patients with PD experience with long-term use of levodopa.
The Science Behind the Solution
Laxxon’s 3D printing technology allows customization of the solid dosage form of the levodopa tablet to tailor and easily modify its release profile. Materials that slow down the metabolism and conversion of levodopa to dopamine are specifically chosen to form a protective outer layer or coating that is more resistant to enzyme activity.
Differing release profiles can be achieved by manipulating the lipid ratio used to manufacture the solid dosage form of the tablet. Lipids are much harder for the digestive system to metabolize compared to other substances, such as carbohydrates or proteins.
The 3D printing process allows these different combinations of select materials to be printed in multiple layers and in varying geometric designs that impact the way the levodopa is released over time. These methods help to control the release of the active pharmaceutical ingredient more gradually over a longer period of time for more sustained and consistent therapeutic effects in the central nervous system.
3D printing facilitates the careful manipulation of the release profile for levodopa allowing for a targeted selection of materials to prevent rapid degradation of the active pharmaceutical ingredient and enabling precise control over the manufacturing process implementing a multi-layered approach and freedom to choose the exact geometric design of the levodopa tablet compared to standard manufacturing methods for oral medications.
Looking Forward Toward the Future for Parkinson’s Care
Laxxon's unique approach to create an extended-release oral formulation of levodopa has the potential to set a new standard in Parkinson's disease management. The Levodopa project aims to provide a solution that overcomes several of the challenges with long-term oral administration of levodopa.
Extending the release of levodopa in a more gradual manner widens the therapeutic window of effect for the drug, allowing more of the active drug to reach the brain in a more continuous flow. This strategy ultimately improves the quality of life for individuals with PD by restoring their ability to control their movements over a longer period of time without the need to take more medicine.
Patients with PD, their caregivers, and their healthcare providers should stay informed about new treatment options and advancements in Parkinson’s care. Laxxon’s extended-release Levodopa project may provide viable solutions to the daily challenges faced by individuals with PD. Why wait to explore this treatment option that can lead to a better quality of life?
Laxxon Medical is dedicated to engineering patented 3D pharmaceutical solutions that optimize products and benefit patients. Our goal is to establish SPID®-Technology as a manufacturing process with the individual and the pharmaceutical partner in mind.
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