Individual dose packaging

Abstract

Aspects of the present invention relate to a separate dose package. The individual dose package may include a single portion cartridge and an outer package surrounding the single portion cartridge as a whole and sealing the single portion cartridge therein, wherein the outer package is child resistant and creates an impermeable barrier that prevents the passage of liquids and gases. The single-serving cartridge may include a cup, at least one pharmaceutically active ingredient provided in the cup, and a lid affixed to the cup. The outer package is of a multi-layer structure and comprises a first layer which is a biaxially oriented polyethylene glycol terephthalate layer, a second layer which is a polyethylene layer, a third layer which is an aluminum foil layer and a fourth layer which is an ionomer layer.

Description

[0001] This application is a divisional application based on a patent application with an application date of June 11, 2019, a priority date of June 11, 2018, an application number of 201980039514.9, and an invention name of "Single Dose Packaging". Technical Field

[0002] Various aspects of the present invention are directed to individual dose packages comprising a single serving pod comprising at least one pharmaceutically active ingredient sealed within a child-resistant outer packaging that provides an impermeable barrier to environmental elements. Background Art

[0003] Single-serve cartridges for automatic brewing machines provide a convenient method of making a single serving of a beverage for consumption. The method is particularly suitable for preparing beverages containing pharmaceutical active ingredients, as users of such products generally seek ease of use and convenience. In addition, user-friendly single-serve cartridges encourage users to use products containing pharmaceutical active ingredients that are beneficial to their health and well-being by simplifying the preparation process. Brewing a single serving of a beverage also avoids waste by avoiding preparing more than the user requires.

[0004] Single-serve cartridges are currently available and are generally intended for use with coffee, tea, etc. Such products are not suitable for use with pharmaceutical active ingredients, which can be attributed to the sensitive nature of the ingredients. Specifically, standard single-serve cartridges cannot protect sensitive pharmaceutical active ingredients from exposure to the environment. It is critical that such products are designed to maintain the quality of the ingredients by preventing exposure to water, oxygen, and other environmental factors. Therefore, sensitive drugs must be packaged in barrier packaging to prevent degradation and maintain efficacy and safety over the duration of their shelf life.

[0005] Additionally, it is important that any product used to contain medications be packaged in child-resistant packaging to prevent children from ingesting potentially hazardous substances. Current statistics indicate that almost one-third of reported pediatric exposures to toxic substances are due to accidental medication ingestion, and over seventy percent of pediatric deaths from such exposures are due to accidental exposure to hazardous substances. Therefore, child-resistant packaging has been an important area of ​​research over the past several decades.

[0006] In addition to being contained in child-resistant packaging, it is also important that the packaging of the active pharmaceutical ingredient is accessible to older people with hand dexterity issues. People with arthritis and people with disabilities have higher rates of per capita pharmaceutical consumption. Opening child-resistant packaging may cause pain in the wrist-metacarpal joints of users with arthritis and similar conditions. This may prevent older people from using such products and obtaining important medicines.

[0007] In view of the above considerations, there is a great need for a single-serving cartridge comprising at least one pharmaceutically active ingredient sealed in a child-resistant and elder-friendly packaging that also provides an impermeable barrier to environmental factors. SUMMARY OF THE INVENTION

[0009] Aspects of the present invention are directed to a single dose package for an automatic brewing machine, comprising: a single serving cartridge comprising: a cup having a bottom portion and a sidewall portion extending from the bottom portion to a rim surrounding an opening and with a space between the bottom portion and the sidewall portion defining an interior space, at least one pharmaceutically active ingredient provided in the interior space of the cup, and a lid attached to the rim of the cup to close the opening and to secure the at least one pharmaceutically active ingredient in the interior space of the cup; and an outer packaging surrounding the entirety of the single serving cartridge and sealing the single serving cartridge therein, wherein the outer packaging is child-resistant and creates an impermeable barrier to the passage of liquids and gases, and wherein the outer packaging is a multilayer structure comprising a first layer being a biaxially oriented polyethylene terephthalate layer, a second layer being a polyethylene layer, a third layer being an aluminum foil layer, and a fourth layer being an ionomer layer.

[0010] The present invention also provides that at least one pharmaceutically active ingredient is acetaminophen, phenylephrine, dextromethorphan, diphenhydramine, ibuprofen, pseudoephedrine, guaifenesin, acetylcysteine, chlorpheniramine, cetirizine, levocetirizine, doxylamine succinate, loratadine, doxylamine or a combination thereof. In one embodiment of the present invention, at least one pharmaceutically active ingredient is acetaminophen. In another embodiment of the present invention, at least one pharmaceutically active ingredient is a combination of acetaminophen, phenylephrine and dextromethorphan. In another embodiment of the present invention, at least one pharmaceutically active ingredient is a combination of acetaminophen, phenylephrine and diphenhydramine. In another embodiment of the present invention, at least one pharmaceutically active ingredient is a combination of guaifenesin and dextromethorphan.

[0011] The present invention also provides that the single dose package is more than 70% child resistant as determined by a child resistant test. In a preferred embodiment of the present invention, the single dose package is 100% child resistant as determined by a child resistant test.

[0012] The present invention also provides that the thickness of the outer packaging is about 70-100 microns. The present invention also provides that the thickness of the first layer of the outer packaging is about 20-30 microns. The present invention also provides that the thickness of the second layer of the outer packaging is about 10-20 microns. The present invention also provides that the thickness of the third layer of the outer packaging is about 7-12 microns. The present invention also provides that the thickness of the fourth layer of the outer packaging is 30-40 microns.

[0013] The present invention also provides an outer package having a water vapor permeability of less than 0.001 g H2O / 100 in 2 / 24 hours. The present invention also provides an outer packaging with an oxygen permeability of less than 0.001cc / 100in 2 / 24 hours.

[0014] The present invention also provides that when laid flat, the outer package has a length of about 130-140 mm and a width of about 80-90 mm.

[0015] The present invention also provides that the fourth layer at one end of the outer package is folded and adhered to the fourth layer at the other end of the outer package to create a sealed portion and seal the single-serving box in the outer package. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] Figure 1 A perspective view of a single serving cartridge of the present invention is illustrated;

[0017] Figure 2 illustrates a perspective view of an individual dose package of the present invention;

[0018] Figure 3 illustrates a perspective view of the outer package of the present invention; and

[0019] Figure 4 A cross-sectional view of the multiple layers of the overpack of the present invention is shown. DETAILED DESCRIPTION

[0020] Aspects of the present invention relate to a single dose package comprising a single serving cartridge, the single dose package being used in an automatic brewing machine to brew a single serving of a beverage comprising at least one pharmaceutically active ingredient. The single serving cartridge is used as a first package of at least one pharmaceutically active ingredient. The single serving cartridge is also packaged and sealed within a second package, which is an outer package that creates a child-resistant and elderly-friendly seal around the package. In addition, the outer package provides a barrier that is impermeable to an environment including, but not limited to, water and oxygen.

[0021] The individual dose package 250 according to the present invention is generally as follows Figure 2 Specifically, Figure 2 There is shown a perspective view of a single serving cartridge 100 comprising at least one pharmaceutically active ingredient 200, packaged and sealed in an outer packaging 300. In use, the single serving cartridge 100 may be removed from the outer packaging 300 and placed in an automatic brewing machine for preparation.

[0022] Figure 1 A perspective view of a single serving box 100 according to the present invention is shown. Figure 1As shown, the single-serving cartridge 100 includes a cup 110 and a lid 120. The cup 110 has a bottom portion 150 and a sidewall portion 160 extending from the bottom portion 150 to a rim 130 surrounding an opening 170. The opening 170 leads to an interior space 140 defined by the sidewall portion 160 and the bottom portion 150 of the cup 110. The lid 120 can be attached to the rim 130 of the cup 110 to create a permanent airtight seal. During a brewing cycle, the lid 120, the bottom portion 150, and / or the sidewall portion 160 can be pierced or otherwise penetrated by an automatic brewing machine, thereby allowing a liquid such as water to enter the cup 110 to mix with the pharmaceutically active ingredient 200, and the resulting beverage can be released from the cup 110.

[0023] Non-limiting examples of materials that can be added to the laminate of the cup 110, lid 120, or outer packaging 300 include polystyrene, ethylene vinyl acetate, polyethylene, biaxially oriented polyethylene terephthalate, polyethylene vinyl acetate, high density polyethylene, cyclic olefin copolymer, biaxially oriented polyamide, ionomer, polytrifluoroethylene, polypropylene, polyester, amorphous polyethylene terephthalate, polyvinyl chloride, polyethylene, aluminum foil, polyethylene terephthalate glycol, polyethylene terephthalate, oriented polyamide, low density polyethylene, polyvinylidene chloride, or any combination thereof. Each layer of the laminate of the cup 110, lid 120, or outer packaging 300 can be adhered to an adjacent layer via an adhesive.

[0024] In a preferred embodiment, the cup 110 including the bottom portion 150 and the sidewall portion 160 can be a multilayer structure made of any suitable material that provides the desired barrier properties. Preferably, the cup 110 comprises at least an outer polystyrene layer, a middle ethylene-vinyl acetate (EVOH) layer, and an inner polyethylene layer.

[0025] During the brewing process of a standard automatic brewing machine, the cup 110 may be exposed to extremely hot liquids; therefore, the cup 110 should maintain its shape and hold the pharmaceutically active ingredient 200 securely in the interior space 140 during the duration of the brewing process. Polystyrene can be used as the outer layer of the cup 110 because it has high stability at extreme temperatures. In addition, the automatic brewing machine can pierce the bottom portion 150 of the cup 110 to allow the beverage made to pass through the cup 110 into the user's container for consumption. Polystyrene is brittle, that is, it will break when it is subjected to stress without significant deformation, and the bottom portion 150 of the cup 110 is easily and reliably pierced by any standard automatic brewing machine. The beverage made for consumption can be any volume. In some embodiments, the beverage made can be 5 fluid ounces, 8 fluid ounces, or 10 fluid ounces. In a preferred embodiment, the beverage made is 8 fluid ounces.

[0026] The cup 110 may include an intermediate EVOH layer that protects the pharmaceutically active ingredient 200 from degradation due to its low oxygen permeability. This increases the shelf life and reliability of the pharmaceutically active ingredient 200 stored in the interior space 140 of the cup 110.

[0027] The pharmaceutical active ingredient 200 provided within the interior space 140 of the cup 110 can be any compound or composition that can be used to treat and / or prevent disease and / or provide overall health and wellness benefits to the user. Non-limiting examples of pharmaceutical active ingredients include over the counter actives, behind the counter actives, prescription drugs, vitamins, minerals, plant-derived materials, energy boosting materials, probiotics, fiber, prebiotics, decongestants, anti-inflammatory drugs, cough suppressants, expectorants, antihistamines, antitussives, analgesics, or any combination thereof.

[0028] The pharmaceutically active ingredient 200 can be acetaminophen, phenylephrine, dextromethorphan, diphenhydramine, ibuprofen, pseudoephedrine, guaifenesin, acetylcysteine, chlorpheniramine, cetirizine, levocetirizine, doxylamine succinate, loratadine, doxylamine, or any combination thereof. However, the present invention can be used for any pharmaceutically active ingredient, or any combination of pharmaceutically active ingredients, or a combination of a pharmaceutically active ingredient and one or more excipients. The pharmaceutically active ingredient 200 can have any suitable form, including but not limited to a powder, a liquid, a gel, or a tablet.

[0029] In a preferred embodiment, the pharmaceutically active ingredient may be a combination of acetaminophen, phenylephrine and dextromethorphan. In another preferred embodiment, the pharmaceutically active ingredient may be a combination of acetaminophen, phenylephrine and diphenhydramine. In another preferred embodiment, the pharmaceutically active ingredient may be acetaminophen.

[0030] In certain embodiments, one or more pharmaceutically active ingredients may be present in an amount of about 1 mg to about 2,000 mg. In embodiments where the pharmaceutically active ingredient 200 comprises acetaminophen, it is present in an amount of about 300 mg to about 1,000 mg. In a preferred embodiment, acetaminophen is present in an amount of about 650 mg. In another preferred embodiment, acetaminophen is present in an amount of about 500 mg. In embodiments where the pharmaceutically active ingredient 200 comprises phenylephrine, it is present in an amount of about 5 mg to about 30 mg. In a preferred embodiment, phenylephrine is present in an amount of about 10 mg. In embodiments where the pharmaceutically active ingredient 200 comprises dextromethorphan, it is present in an amount of about 5 mg to about 30 mg. In a preferred embodiment, dextromethorphan is present in an amount of about 20 mg. In embodiments where the pharmaceutically active ingredient comprises diphenhydramine, it is present in an amount of about 5 mg to about 50 mg. In a preferred embodiment, diphenhydramine is present in an amount of about 25 mg.

[0031] The non-limiting example of excipients includes spices, fillers, disintegrants, glidants, lubricants, antioxidants, sweeteners, pigments, preservatives, lubricants, adsorbents or its arbitrary combination.Suitable spices may include, for example, peppermint, menthol, peppermint, wintergreen oil, sweet mint, green mint, vanillin, caramel, chocolate, coffee, cinnamon, cloves, citrus, lemon, green tea, white tea, chamomile, lime, orange, grape, cherry, strawberry, fruit punch (fruit punch), honey, honey lemon, other fruit flavors or its arbitrary combination.Suitable fillers may include, for example, maltodextrin, silicon dioxide, sodium citrate, tricalcium phosphate, anhydrous citric acid, sodium citrate, various levels of microcrystalline cellulose (such as Avicel PH101, Avicel PH102 & Avicel PH200), corn starch or its arbitrary combination. Suitable disintegrants may include, for example, sodium starch glycolate [Explotab], cross-linked polyvinyl pyrrolidone, corn starch, gum arabic, cross-linked sodium carboxymethylcellulose [Ac-di-sol], sodium carboxymethylcellulose, aluminum magnesium silicate, alginate, or any combination thereof. Suitable glidants may include, for example, talc, corn starch, stearic acid, calcium stearate, polyethylene glycol, silicon dioxide, sodium stearyl fumarate, magnesium stearate, vegetable oil and mineral oil, or any combination thereof. Suitable lubricants may include, for example, magnesium stearate, stearic acid and pharmaceutically acceptable alkali metal salts thereof, calcium stearate, sodium stearate, Cab-O-Sil, Syloid, sodium lauryl sulfate, sodium chloride, magnesium lauryl sulfate, talc, or any combination thereof. Suitable antioxidants may include, for example, alpha-tocopherol, beta-tocopherol, gamma-tocopherol, delta-tocopherol, butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA), ascorbic acid, fumaric acid, malic acid, ascorbyl palmitate, propyl gallate, sodium ascorbate, sodium pyrosulfite, or any combination thereof. Suitable sweeteners may include, for example, acesulfame potassium, aspartame, sucrose, or any combination thereof. Suitable pigments may include, for example, FD&C blue No. 1, FD&C red No. 40, D&C yellow No. 10, FD&C blue No. 1, FD&C red No. 40.

[0032] In a preferred embodiment, the lid 120 can be a multi-layer structure made of any suitable material that provides the desired barrier properties. Preferably, the lid 120 includes at least an outer primer layer, an intermediate aluminum foil layer, and an inner sealing layer. The lid 120 can be securely and permanently sealed to the edge 130 of the cup 110 via the inner sealing layer of the lid 120, and the active pharmaceutical ingredient 200 is in the interior space 140 of the cup 110. The inner sealing layer can create an airtight seal between the lid 120 and the cup 110, which also protects the active pharmaceutical ingredient 200.

[0033] The overall thickness of the cover 120 is about 65 microns to about 82 microns. Preferably, the overall thickness of the cover 120 is about 73.8 microns. The thickness of the outer primer layer is about 4 microns to about 9 microns. Preferably, the outer primer layer has a thickness of about 6.8 microns. The thickness of the intermediate aluminum foil layer is about 34 microns to about 40 microns. Preferably, the intermediate aluminum foil layer has a thickness of about 37 microns. The thickness of the inner sealing layer is about 27 microns to about 33 microns. Preferably, the inner sealing layer has a thickness of about 30 microns. The total thickness of the cover 120 after embossing is about 100 microns to about 150 microns. Preferably, the total thickness of the cover 120 after embossing is about 125 microns. The overall multilayer structure of the cover 120 has a weight of less than 0.05 g / 100 in. 2 / 24 hours water vapor transmission rate.

[0034] Although the cup 110 and lid 120 as described above provide barrier properties, they themselves may not be sufficient to contain the sensitive pharmaceutical active ingredients 200 of the present invention. Therefore, the single-serving cartridge 100 can be further packaged and sealed in a multi-layer outer packaging 300 to provide additional protection against water, oxygen and other environmental factors. The outer packaging 300 can surround the entirety of the single-serving cartridge 100, thereby sealing the single-serving cartridge 100 in the outer packaging 300.

[0035] Specifically, outer package 300 realizes the required waterproof and child-proof level of pharmaceutical products.This is the required higher standard than the manufacturer of the single-portion material box for tea, coffee or other such beverages.When lying on the surface without sealing single-portion material box 100, the length of outer package 300 can be about 135mm to about 140mm and the width is about 80mm to about 90mm.Preferably, when lying on the surface without sealing single-portion material box 100, the length of outer package 300 is about 135mm, and the width of outer package 300 is about 86.5.In addition, the gross thickness of outer package 300 can be about 70 microns to about 100 microns.Preferably, the thickness of outer package 300 is about 79.2 microns.

[0036] Figure 4 The multilayer cross-sectional view of outer package 300 of the present invention is illustrated.Outer package 300 can have any suitable material that provides desirable barrier properties to make.In a preferred embodiment, outer package 300 comprises the first layer 410 that is biaxially oriented polyethylene terephthalate (BoPET) layer.The first layer 410 is the polyester film made by stretching in two different directions to improve the polyethylene terephthalate of mechanical orientation.The first layer 410 provides some beneficial properties for the present invention, includes but not limited to, high tensile strength, durability, barrier properties and transparency.

[0037] In addition, the thickness of the first layer 410 of the outer package 300 is about 20 microns to about 30 microns. Preferably, the thickness of the first layer 410 is about 23 microns. The thickness of the first layer 410 increases the strength of the outer package 300 and allows it to be child-proof. Usually, the thickness of the BoPET layer used for similar products will be much smaller; however, such similar products will not be child-proof and therefore cannot be used for pharmaceutical ingredients.

[0038] In a preferred embodiment, the outer package 300 includes a second layer 420 which is a polyethylene (PE) layer having a thickness of about 10 microns to about 20 microns. Preferably, the thickness of the second layer 420 is about 13 microns. Specifically, the second layer 420 can be a white PE layer. The second layer 420 can provide a white background for printing and bond the first layer 410 and the third layer 430.

[0039] In a preferred embodiment, the outer package 300 includes a third layer 430 that is an aluminum foil layer. The thickness of the third layer 430 is about 7 microns to about 12 microns. Preferably, the thickness of the third layer 430 is about 8.9 microns. The third layer 430 prevents liquid and gas (including water and oxygen, etc.) from passing through the outer package 300. Specifically, due to the sensitivity of the molecular structure of aluminum foil to environmental factors, it has produced a strong barrier that can be ideally used for drug ingredients.

[0040] The third layer 430 eliminates exposure to liquids and gases; thereby extending the shelf life of the present invention and maintaining the quality and efficacy of the pharmaceutically active ingredient 200 stored in the cup 110. In addition, the third layer 430 is durable and strong, while also being lightweight and malleable; therefore, it is ideal for packaging products of various shapes and sizes without any loss of its barrier properties.

[0041] In a preferred embodiment, the outer packaging includes a fourth layer 440 that is an ionomer layer. The thickness of the fourth layer 440 is about 30 microns to about 40 microns. Preferably, the thickness of the fourth layer 440 is about 34.3 microns. The fourth layer 440 is a seal and can be folded upon itself to create a seal around the single-serving box 100.

[0042] like Figure 4 As can be seen in FIG. 1 , the first layer 410 can be the outermost layer on the outside of the outer package 300. The second layer 420 can be disposed between the first layer 410 and the third layer 430. The third layer 430 can be disposed between the second layer 420 and the fourth layer 440. The fourth layer 440 can be the innermost layer on the sealing side or inner side of the outer package 300.

[0043] Figure 3 A perspective view of a single serving cartridge 100 sealed in an outer packaging 300 is shown. Figure 3As can be seen in the figure, the fourth layer 440 at one end of the outer package 300 can be sealed to the fourth layer 440 at the other end of the outer package 300 to produce a sealed portion 310. The sealed portion 310 provides a perfect seal to further protect the active pharmaceutical ingredient 200 stored in the single-serving box 100.

[0044] The water vapor transmission rate of the outer packaging 300 is less than 0.005g H2O / 100in 2 / 24 hours. Preferably, the water vapor permeability of the outer package 300 is less than 0.001g H2O / 100in 2 / 24 hours. The water vapor transmission rate of the outer package is tested at a temperature of 100°F and a relative humidity of 90%. In addition, the oxygen transmission rate of the outer package 300 is less than 0.005cc / 100in 2 / 24 hours. Preferably, the oxygen permeability of the outer package 300 is less than 0.001cc / 100in 2 / 24 hours. The oxygen permeability is tested at a temperature of 73°F and a relative humidity of 0%. Therefore, the outer package 300 has excellent oxygen and water barrier properties, which is ideal for the active pharmaceutical ingredient 200 that can be used in the individual metered package 250.

[0045] In addition, the outer packaging 300 provides a child-resistant and tear-resistant packaging for the single-serving cartridge 100. Tear-resistant refers to a material that can undergo a reasonable level of stress and / or deformation without experiencing a significant loss of integrity when subjected to forces that can be applied by an individual. The important point is that the outer packaging 300 is child-resistant, thereby preventing children from ingesting potentially dangerous substances that may be stored in the cup 110 of the present invention, such as the pharmaceutically active ingredient 200.

[0046] The present invention is subjected to standardized child-proof testing according to 16.CFR§1700 Poison Prevention Packaging. Failure of the test is defined as any child opening the package or gaining access to the contents of the package. In one embodiment, the present invention can be child-proof and can be given a rating called an F value. The F value is the number of unit doses for which access is considered to be a failure of the test. The F value is determined based on the number of unit doses that can cause serious bodily injury or serious illness to a 25-pound (11.4 kg) child. In one embodiment of the present invention, the individual dose package 250 can be F=1 package. In another embodiment, the individual dose package 250 of the present invention can be F=3 packages. In another embodiment, the individual dose package 250 of the present invention can be F=4 packages. In another embodiment, the individual dose package 250 of the present invention can be F=5 packages. In a preferred embodiment of the present invention, the individual dose package is F=2 packages.

[0047] The conclusion of the child-resistant test is that the single dose package 250 is more than 70% child-resistant when the package is F=1, F=2, F=3, F=4 or F=5 packages. In another embodiment, the single dose package is more than 80% child-resistant when the package is F=1, F=2, F=3, F=4 or F=5 packages. In a preferred embodiment, the single dose package is 100% child-resistant when the package is F=1, F=2, F=3, F=4 or F=5 packages.

[0048] In addition, the outer package 300 of the present invention is subjected to the elderly test according to 16.CFR§1700 Poison Prevention Packaging to ensure that adults with dexterity problems can use the single-serving box 100. In one embodiment, more than 90% of the elderly tested successfully opened the outer package 300 using scissors or other reasonable means. In a preferred embodiment, 100% of the elderly tested successfully opened the outer package 300 using scissors or other reasonable means.

[0049] Other aspects of the invention may relate to methods of treating symptoms of colds and / or flu, allergies or other diseases, comprising preparing a beverage as described herein and administering or consuming the prepared beverage. Other aspects of the invention may relate to the use of a beverage prepared as described herein for treating colds and / or flu, allergies or other diseases.

[0050] Example 1

[0051] The stability and appropriate shelf life of the present invention are described in Example 1. Specifically, stability studies were conducted on the following embodiment of the present invention: wherein the pharmaceutical active ingredient 200 is a combination of 650 mg acetaminophen, 10 mg phenylephrine, and 20 mg dextromethorphan.

[0052] The present invention was tested under the following conditions: long-term storage conditions at 25°C and 60% relative humidity, intermediate storage conditions at 30°C and 65% relative humidity, and accelerated storage conditions at 40°C and 75% relative humidity.

[0053] As shown in Tables 1-3 below, the conclusion of the study is that the evaluation data are generally consistent with the specifications at all time points and storage conditions. Specifically, at all time points and storage conditions, the data generated by the appearance of the particles and solutions are consistent with the specifications. At all time points and storage conditions, the data generated by each activity determination are consistent with the specifications, and the changes over time are minimized. At all time points and storage conditions, the data generated by acetaminophen show that there is no increase in degradation, and the maximum result is less than 0.05%. At each planned time point and storage condition, the data generated by PHL021, PHL033, PHL052+PHL021-2, the maximum value of unspecified degradation products, and the sum of total degradation products are all within the specification limits. At each planned time point and storage condition, DEX921, DEC922-1, unspecified degradation products, and the maximum value of total degradation products and the sum of total degradation products are all within the specification limits. The microbial purity of the present invention has been evaluated for total aerobic counts, total yeast counts, and mold counts, as well as specific microorganisms Escherichia coli. For all samples to be tested, microbial purity has been shown to meet the requirements of the final product specification.

[0054] Based on the above results, the stability study concluded that there is a high degree of confidence that the present invention is sufficiently robust and that the single serving cartridge 100 can provide long term stability for the pharmaceutically active ingredient 200 within the interior space 140 of the cup 110 .

[0055] The long-term and accelerated stability data verify that the present invention is not adversely affected when packaged in a single serving cartridge 100. Therefore, the present invention has a shelf life of 24 months when packaged in a single serving cartridge 100 of the present invention and stored at a temperature below 25°C or equivalent conditions.

[0056] Temperature cycling studies were conducted to investigate the stability of the present invention when stored under freezing conditions and then thawed. For freeze-thaw exposure, the present invention was exposed at -20°C for 12 hours, followed by 10°C for 12 hours, for a total of 5 cycles and 10 cycles. In addition, a high temperature static study was conducted at 50°C for 2 weeks. The results of this study concluded that the present invention is not temperature sensitive to freeze-thaw conditions and high temperatures.

[0057] Notes to Table 1

[0058] Note: Failure = Test exceeds Spec(s)sS

[0059] NT = Not Tested, ND = Not Detected, NS = Not Planned

[0060] NMT = not more than

[0061] NR = No result

[0062] N / A = Not Applicable

[0063]

[0064]

[0065]

[0066]

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[0068]

[0069]

[0070]

[0071] Example 2

[0072] The stability and appropriate shelf life of the present invention are described in Example 2. Specifically, the stability study was conducted on the following embodiment of the present invention: wherein the pharmaceutical active ingredient 200 is a combination of 650 mg acetaminophen, 10 mg phenylephrine and 25 mg diphenhydramine.

[0073] The present invention was tested under the following conditions: long-term storage conditions at a temperature of 25°C and a relative humidity of 60%, intermediate storage conditions at a temperature of 30°C and a relative humidity of 65%, and accelerated storage conditions at a temperature of 40°C and a relative humidity of 75%.

[0074] As can be seen in Tables 4-6 below, the conclusion of the study is that the evaluation data are generally consistent with the specifications at all time points and storage conditions. Specifically, at all time points and storage conditions, the data generated by the appearance of the particles and the solution are consistent with the specifications. At all time points and storage conditions, the data generated by each activity determination are consistent with the specifications, and the changes over time are minimized. At all time points and storage conditions, the data generated by acetaminophen show that the degradation has not increased, and the maximum result is less than 0.05%. At each planned time point and storage condition, the data generated by PHL021, PHL033, PHL052+PHL021-2, the maximum value of unspecified degradation products, and the sum of total degradation products are all within the specification limits. At each planned time point and storage condition, DEX921, DEC922-1, unspecified degradation products, and the maximum value of total degradation products and the sum of total degradation products are all within the specification limits. The microbial purity of the present invention has been evaluated for total aerobic count, total yeast count and mold count, and specific microbial Escherichia coli. For all samples tested, microbiological purity was shown to meet the requirements of the final product specifications.

[0075] Based on the above results, the stability study concluded that there is a high degree of confidence that the present invention is sufficiently robust and that the single serving cartridge 100 can provide long term stability for the pharmaceutically active ingredient 200 within the interior space 140 of the cup 110 .

[0076] The long-term and accelerated stability data verify that the present invention is not adversely affected when packaged in a single serving cartridge 100. Therefore, the present invention has a shelf life of 24 months when packaged in a single serving cartridge 100 of the present invention and stored at a temperature below 25°C or equivalent conditions.

[0077] Temperature cycling studies were conducted to investigate the stability of the present invention when stored under freezing conditions and then thawed. For freeze-thaw exposure, the present invention was exposed at -20°C for 12 hours, followed by 10°C for 12 hours, for a total of 5 cycles and 10 cycles. In addition, a high temperature static study was conducted at 50°C for 2 weeks. The results of this study concluded that the present invention is not temperature sensitive to freeze-thaw conditions and high temperatures.

[0078]

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[0080]

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[0086]

[0087] Example 3

[0088] Example 3 details the test methods and test results of the child-resistant test conducted on the present invention to ensure that it complies with The Poison Prevention Packaging Act 1970 Regulations and The Code of Federal Regulations Title 16: Part 1700.2. The test methods and test results are detailed below.

[0089] Child-resistant testing method:

[0090] Twenty-five boys and 25 girls aged 42 months to 52 months (inclusive) were tested in pairs in two separate testing settings. Thirty percent of the children were aged 42-44 months, 40% were aged 45-48 months, and 30% were aged 49-51 months. All children were prepared and provided detailed information in advance.

[0091] First, a pair of children were placed in a room, handed the same package, and prompted by an administrator to "please try to open it for me". Each child was then given 5 minutes to try to open his / her package. During the entire test, the administrator observed the children closely and did not influence the children in any way, either verbally or non-verbally. The children were allowed to move freely to handle their packages, that is, they were allowed to stand up, sit on the floor, hit or pry open the packages. The children were also allowed to talk to each other about opening the packages and could observe each other trying to open the packages. If a child opened the package, the administrator said "thank you" and took the package back from the child and placed it out of the child's reach. The children were not required to open the package a second time.

[0092] At the end of the 5 minutes, if neither child has opened his / her package, the administrator demonstrates how to open the package. The administrator demonstrates using a packaged individual demonstration. Prior to the demonstration, the children are asked to set their packages aside and are not allowed to continue attempting to open their packages. During the demonstration, the administrator holds the package approximately two feet from the child and opens the package at a normal pace, as if the administrator were about to use the contents. The administrator does not exaggerate any actions. The administrator also does not discuss or describe how to open the package.

[0093] After the demonstration, the administrator instructed the children to begin the second 5-min test period by prompting, “Now you try to open your packages.” If one or both children did not use their teeth to open their packages during the first 5-min test period, the administrator instructed the children, “If you want, you can use your teeth,” before starting the second 5-min test period. The administrator then observed the children during the second 5-min test period or until both children opened their packages, whichever came first.

[0094] Child-resistant test results:

[0095] Zero openings were recorded during the first 5-minute test period (before demonstration). In addition, zero openings were recorded during the second 5-minute test period (after demonstration). This corresponds to a total percentage of 0.00% for the entire 10-minute test, which is within the permissible range of US16 CFR§1700.20. Therefore, the present invention meets the child-resistant testing requirements of US16 CFR§1700.20, as shown in Table 7.

[0096] These results are based on the following assumptions: opening a package is defined as a situation where a child has access to 1 (or more) units contained in the package. This corresponds to a failure rate of F = 1. Table 7 below lists the number of opened packages that constitute a pass, require continued testing, or constitute a failure during the first 5-minute test period and the entire 10-minute test according to US16CFR§1700.20.

[0097] Table 7: Open Numbers – Acceptance (Pass), Continue Testing, and Rejection (Failure) Criteria

[0098]

[0099] Example 4

[0100] Example 4 details the test methods and test results of the elderly testing of the present invention to ensure compliance with The Poison Prevention Packaging Act of 1970 Regulations and The Code of Federal Regulations Title 16: Part 1700. 20. The test methods and test results are detailed below.

[0101] Testing methods for the elderly:

[0102] The test was conducted on 100 participants, 70% of whom were female and 30% were male. 25% of the participants were between 50-54 years old, 25% of the participants were between 55-59 years old, and 50% of the participants were between 60-70 years old. Each participant took the test alone and there were no other participants or bystanders present. The test was conducted in a well-lit and distraction-free space.

[0103] The administrator began the first 5-minute testing period by instructing the participant to open the provided package following the instructions on the package. The participant was allowed up to 5 minutes to read the instructions and open the package. After 5 minutes, or when the participant opened the package, whichever came first, the administrator took all test materials from the participant.

[0104] Next, the administrator started the second test period by giving the participant another identical package. The second test period lasted 1 minute. The administrator instructed the participant that this was an identical package and to open it again according to the instructions. Additionally, the administrator informed the participant that to open the package, they needed to cut along the end seal with scissors. After the second test period, or when the participant opened the package, whichever came first, the administrator took all the test materials from the participant.

[0105] Test results for the elderly:

[0106] 16 CFR § 1700.20 allows for a 10% unsuccessful opening rate. The results of the elderly test conducted according to the described procedure showed that zero unsuccessful attempts to open the package were recorded in the first test period. In the second test period, zero unsuccessful attempts to open the package were recorded. For the entire 10-minute test, this corresponds to a total percentage of 0.00%, which is within the permissible range of US 16 CFR § 1700.20. Therefore, the present invention meets the adult testing requirements of 16 CFR § 1700.20.

Claims

1. A single dose package for an automatic brewing machine, comprising: Single serving box containing: a cup having a bottom portion and a side wall portion extending from the bottom portion to an edge surrounding an opening, the space between the bottom portion and the side wall portion defining an interior space, at least one pharmaceutically active ingredient provided in the interior space of the cup, and a lid affixed to the rim of the cup thereby closing the opening and enclosing the at least one pharmaceutically active ingredient within the interior space of the cup; and an outer packaging surrounding the entirety of the single-serving box and sealing the single-serving box therein, wherein the outer packaging creates an impermeable barrier to the passage of liquids and gases, and The outer packaging is a multilayer structure comprising a first layer of biaxially oriented polyethylene terephthalate, a second layer of polyethylene, a third layer of aluminum foil and a fourth layer of ionomer.

2. The single dose package of claim 1, wherein the at least one pharmaceutically active ingredient is acetaminophen, phenylephrine, dextromethorphan, diphenhydramine, ibuprofen, pseudoephedrine, guaifenesin, acetylcysteine, chlorpheniramine, cetirizine, levocetirizine, doxylamine succinate, loratadine, doxylamine, or a combination thereof.

3. The individual dose package according to claim 2, wherein the at least one pharmaceutically active ingredient is acetaminophen.

4. The individual dose package of claim 2, wherein the at least one pharmaceutically active ingredient is a combination of acetaminophen, phenylephrine, and dextromethorphan.

5. The individual dose package of claim 2, wherein the at least one pharmaceutically active ingredient is a combination of acetaminophen, phenylephrine, and diphenhydramine.

6. The individual dose package of claim 2, wherein the at least one pharmaceutically active ingredient is a combination of guaifenesin and dextromethorphan.

7. The individual dose package of claim 1, wherein the single dose package is more than 70% child resistant as determined by child resistance testing.

8. The individual dose package of claim 6, wherein the single dose package is 100% child resistant as determined by child resistance testing.

9. The individual dose package of claim 1, wherein the outer package has a thickness of about 70-100 microns.

10. The individual dose package of claim 1, wherein the first layer of the outer packaging has a thickness of about 20-30 microns.

11. The individual dose package of claim 1, wherein the second layer of the outer packaging has a thickness of about 10-20 microns.

12. The individual dose package of claim 1, wherein the third layer of the outer packaging has a thickness of about 7-12 microns.

13. The individual dose package of claim 1, wherein the fourth layer of the outer packaging has a thickness of about 30-40 microns.

14. The individual dose package of claim 1, wherein the outer package has a volume fraction of less than 0.001 g H2O / 100 in 2 / 24 hours water vapor transmission rate.

15. The individual dose package of claim 1, wherein the outer package has a volume fraction of less than 0.001 cc / 100 in. 2 / 24 hours oxygen transmission rate.

16. The individual dose package of claim 1, wherein the outer package has a length of about 130-140 mm and a width of about 80-90 mm when laid flat.

17. The individual dose package of claim 1, wherein the fourth layer at one end of the outer package is folded and adhered to the fourth layer at the other end of the outer package to create a sealed portion and seal the single serving cartridge in the outer package.

18. A multi-layer outer package comprising: a first layer which is a biaxially oriented polyethylene terephthalate layer; A second layer, which is a polyethylene layer; The third time, it is an aluminum foil layer; and a fourth layer, which is an ionomer layer, Wherein the outer packaging is child-resistant and creates an impermeable barrier to the passage of liquids and gases.

19. The multi-layer overpack of claim 17, wherein the multi-layer overpack is more than 70% child-resistant as determined by a child-resistant test.

20. The multi-layer overpack of claim 18, wherein the multi-layer overpack is 100% child resistant as determined by child-resistant testing.

21. The multi-layer overpack of claim 17, wherein the first layer of the multi-layer overpack has a thickness of about 20-30 microns.

22. The multi-layer overpack of claim 17, wherein the second layer of the multi-layer overpack has a thickness of about 10-20 microns.

23. The multi-layer overpack of claim 17, wherein the third layer of the multi-layer overpack has a thickness of about 7-12 microns.

24. The multi-layer overpack of claim 17, wherein the fourth layer of the multi-layer overpack has a thickness of about 30-40 microns.

25. The multilayer overpack of claim 17, wherein the multilayer overpack has a content of less than 0.001 g H2O / 100 in 2 / 24 hours water vapor transmission rate.

26. The multi-layer overpack of claim 17, wherein the multi-layer overpack has a viscosity less than 0.001 cc / 100 in. 2 / 24 hours oxygen transmission rate.

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