It has been a standard of care for cardiovascular patients to use aspirin to prevent and manage heart disease and stroke. A low-dose of aspirin (81 mg daily) has been proven to lower the risk of cardiovascular disease. At the same time, sublingual nitroglycerin (0.4 mg) is prescribed for acute angina pectoris or for its prophylaxis (activities or situations likely to provoke an anginal attack).
I have identified a key unmet need for these cardiovascular patients: a combination of aspirin and nitroglycerin. The combination enables the patient to carry a single tablet, as opposed to taking two separate tablets during a cardiovascular event. The convenience and efficacy of the combination could make a difference during cardiovascular events, which in turn creates an attractive marketing opportunity. To this end, a Provisional US Patent (Application No. 62736166), was submitted in September 2018. This patent is being offered for sale to interested parties. The title of the invention is: Dosage Forms For Administering Combination of Aspirin and Nitroglycerin.
According to the American Heart Association’s 2019 Heart Disease and Stroke Statistics Update, cardiovascular disease is the leading cause of death globally, accounting for more than 17.6 million deaths per year in 2016, and this number is expected to grow to more than 23.6 million by 2030. In US alone, there were 840,678 deaths in 2016 due to such diseases. Heart disease is the leading cause of death for both men and women. There were approximately 121.5 million Americans that had some form of cardiovascular disease in between 2013-16. These figures speak volumes for the number of heart patients that would be potentially benefited from this patent. Furthermore, between 2014-2015, direct and indirect medical costs of total cardiovascular diseases as well as stroke were about $351.2 billion and have been projected to significantly increase to $749 billion in 2035.
When warning signs of a heart attack occur such as: shortness of breath, chest pain, upper body pain, arm pain, neck, back, jaw, cold sweats, nausea, dizziness, etc., the individual must immediately place the sublingual pill identified within the patent under their tongue. Currently when a cardiovascular event occurs, the individual must take a separate nitroglycerin pill, as well as chew an aspirin tablet to avoid damage to the heart in the form of a heart attack, angina, stroke, or other cardiovascular events.
The medical community has identified certain risk factors that increase the potential to develop plaque in the coronary arteries, which causes the arteries to narrow and is commonly identified as atherosclerosis. Due to an aspirin’s antiplatelet activity, the risk of heart attacks is decreased.
Additionally, nitrates are critical to dilate arteries which increases blood flow to the heart muscle. Combination of the two drugs is usually recommended during emergency heart conditions.
The patent will benefit cardiovascular patients during a heart episode by requiring the patient to take only one pill, as opposed to the present-day method of taking two pills to minimize potential damage to the heart.
The current strategy of administering sublingual nitroglycerin as well as chewable aspirin in case of an emergency heart condition has shortcomings in terms of low patient compliance and adherence, as one may easily forget to carry the two medications together all the time, and this can take severe toll on one’s life. The invention in this patent describes formulating a single dosage form, preferably sublingual, comprising of both, aspirin and nitroglycerin. In addition to the formulation, a novel design for packaging of the combined dosage form as well as additional nitroglycerin dosage required in extremely severe conditions has also been elaborated.
This technology would not only reduce the need of carrying two different drug containers all the time; but administering aspirin via the sublingual route would also improve its onset of pharmacological action and reduce the dose requirements as well. Quick onset of action is definitely of the utmost importance, as the drug must act within minutes in an emergency condition, and sublingual route has superior absorption capabilities, being about 3-10 times higher than the oral route. With numerous advantages to offer, the novel technology described in this patent, if available to the prescribers, would probably be their first choice for prescription for heart-related emergency conditions.
Formulation development of fixed-dose combination containing nitroglycerin and aspirin in a single tablet designed for sublingual administration, has been proposed. A single layer monolithic sublingual tablet, in which aspirin and nitroglycerin will be mixed and compressed into one tablet, can be designed as shown in Fig 1a.
Other tablet designs, combining sublingual nitroglycerin and chewable aspirin, as bilayer, core tablet-in-tablet, or two-sided tablet are additional potential alternatives. These have been presented in Fig 1b-d:
c. Core tablet-in-tablet
The combined tablet may be prescribed to be taken immediately in case of an emergency, followed by the administration of one nitroglycerin tablet 5 minutes after the initial combination tablet, and if the symptoms persist, the user may take another nitroglycerin tablet 5 minutes from the last nitroglycerin tablet taken. It must be noted that within 15 minutes from the administration of the first combination tablet, the user is limited to a maximum of three tablets which includes the initial combination tablet within a fifteen-minute period in case of severe angina pain. For this purpose, a regular nitroglycerin tablet should be distinguishable from the proposed combination dosage. Fig 2. shows a proposed packaging design for 30 dispensing combination dosage forms of aspirin and nitroglycerin, along with two additional nitroglycerin tablets without the aspirin.
The use of fixed dose combination (FDC) drug therapies has been accepted worldwide with increasing number of products to enhance the therapeutic efficacy and safety, as well as improved patient compliance. The criteria to choose a design for an FDC formulation is as follows: If the two medications show physicochemical compatibility, and exert similar dissolution profile, a monolithic system can be designed in which the two APIs (aspirin and nitroglycerin) will be mixed and compressed into one tablet, with other appropriate excipients such as binder, disintegrant, etc. In case of non-compatibility, studies show that a bilayer or core tablet in tablet would be more practical.
Interested parties should contact Harry S. Bloch at (267) 252-8956, or online at Invent1836@gmail.com. There is a preference for an outright sale of the Provisional Patent rights, but a joint venture will also be considered.
About the author
Harry Bloch is the Inventor and has been recognized by the Wall Street Journal, The New York Times, Parents Magazine, featured in a Viking Penguin publication, appeared on television, and numerous other media outlets. Mr. Bloch has developed additional patents in diversified fields including electro-optics and healthcare products.