RU2800895C2 - Packaging with individual dose - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: group of inventions relates to medical packages with an individual dose. The individual dose package for use with an automatic cooker contains a single dose capsule comprising a cup having a bottom and a side wall extending from the bottom to a rim surrounding the opening, with the space between the bottom and the side wall defining the interior space. The pharmaceutical active ingredient is in the interior of the cup. The lid is attached to the rim of the cup, thereby closing the opening and keeping the pharmaceutical active ingredient within the interior of the cup. The outer wrapper surrounds the entire single dose capsule and seals the single dose capsule. The outer wrap creates an impermeable barrier that prevents the penetration of liquids and gases. The outer wrapper is a multilayer structure including a first layer which is a biaxial oriented polyethylene terephthalate layer, a second layer which is a polyethylene layer, a third layer which is an aluminium foil layer, and a fourth layer which is an ionomer layer. The outer wrap is 100% childproof with zero openings within a 10-minute period. A multilayer outer wrapper is disclosed.

EFFECT: providing packaging that is child-proof and accessible to older adults with an impenetrable barrier against environmental factors.

24 cl, 4 dwg, 7 tbl

Description

Field of invention

Objects of the present invention are directed to a single dose package comprising a single dose capsule containing at least one pharmaceutical active ingredient sealed in a child-resistant wrapper that provides an impermeable barrier against environmental factors.

State of the art

Single serving capsules that work with automatic brewing machines allow you to easily prepare one serving of drink for consumption. This method is particularly useful for preparing beverages containing pharmaceutical active ingredients, as users of such products typically seek ease of use and convenience. In addition, convenient single-use capsules encourage users to use products containing pharmaceutical active ingredients that are beneficial to their health and well-being by streamlining the preparation process. Brewing a single drink also prevents waste, as it avoids having to prepare more than the user needs.

Disposable capsules are currently available and are generally intended to be used with coffee, tea, and the like. Such products are not suitable for use with pharmaceutical active ingredients due to the sensitivity of such ingredients. In particular, standard single serving capsules are unable to protect sensitive pharmaceutical active ingredients from environmental attack. It is imperative that such products are designed to maintain the quality of the ingredients by preventing exposure to water, oxygen and other environmental factors. Therefore, sensitive pharmaceuticals must be packaged in barrier packaging to prevent degradation and maintain efficacy and safety throughout their shelf life.

In addition, it is vital that any products used to house pharmaceuticals are packaged in child-resistant packaging to prevent children from ingesting potentially hazardous substances. Current statistics show that almost a third of reported pediatric exposures to toxic substances are due to unintentional drug use, and that more than seventy percent of deaths in children are due to unintentional exposure to hazardous substances. Thus, child-resistant packaging has been an area of significant research over the past few decades.

In addition to being placed in a child-resistant package, it is equally important that the packaging for pharmaceutical active ingredients be suitable for use by older people with hand mobility problems. Consumers with arthritis and people with disabilities have higher per capita consumption of pharmaceuticals. Opening a child-proof package may cause a painful strain on the carpometacarpal joints in users suffering from arthritis or similar conditions. This may prevent older people from using such products and accessing life-saving pharmaceuticals.

Based on the problems noted above, a single serving capsule containing at least one pharmaceutical active ingredient that is sealed in a child-resistant, senior-adult-accessible package that also provides an impenetrable barrier against environmental factors is highly desirable.

The essence of the invention

Objects of the present invention relate to a single dose package for use with an automatic brewing machine, comprising: a single dose capsule including a cup having a bottom and a side wall extending from the bottom to a rim surrounding the opening, a space between the bottom and the side wall, defining an interior of at least one pharmaceutical active ingredient provided in the interior of the cup and a lid attached to the rim of the cup, thereby closing the opening and holding the at least one pharmaceutical active in the interior of the cup; and an outer wrapper enclosing the entire single-dose capsule and sealing the single-dose capsule in itself, wherein the outer wrapper is childproof and provides an impermeable barrier to the passage of liquids and gases, and wherein the outer wrapper is a multilayer structure including a first a layer that is a biaxially oriented polyethylene terephthalate layer, a second layer that is a polyethylene layer, a third layer that is an aluminum foil layer, and a fourth layer that is an ionomer layer.

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

The present invention further provides that the individual dose package is greater than 70% childproof as determined by a child safety test. In a preferred embodiment of the present invention, the single dose package is 100% childproof as determined by a child safety test.

The present invention also provides that the outer wrap has a thickness of about 70-100 microns. The present invention further provides that the first layer of the outer wrap has a thickness of about 20-30 microns. The present invention also provides that the second layer of the outer wrap has a thickness of about 10-20 microns. The present invention further provides that the third layer of the outer wrap has a thickness of about 7-12 microns. The present invention further provides that the fourth layer of the outer wrap has a thickness of 30-40 microns.

The present invention also provides that the outer wrap has a moisture vapor transmission rate of less than 0.001 g H ₂ O/100 inches ² /24 hours. The present invention also provides that the outer wrap has an oxygen transmission rate of less than 0.001 cm ³ /100 inches ² /24 hours.

The present invention further provides that the outer wrap has a length of about 130-140 mm and a width of about 80-90 mm in the horizontal position.

The present invention further provides that a fourth layer of one end of the overwrap is folded and adhered to a fourth layer of the other end of the overwrap to form a sealed portion and seal the single dose capsule within the overwrap.

BRIEF DESCRIPTION OF THE DRAWINGS

In FIG. 1 is a perspective view of a single dose capsule of the present invention;

Fig. 2 is a perspective view of the individual dose package of the present invention;

In FIG. 3 is a perspective view of an overwrap according to the present invention; And

On FIG. 4 shows a cross section of the layers of the outer wrap according to the present invention.

Detailed description

Objects of the present invention relate to a single dose package comprising a single dose capsule for use in an automatic brewing machine to prepare a single serving of a beverage containing at least one pharmaceutical active ingredient. The single dose capsule serves as the primary packaging for at least one pharmaceutical active ingredient. The single dose capsule is further packaged and sealed in a secondary pack, which is an outer wrapper that creates a child-resistant, senior-accessible package around the capsule. In addition, the outer wrapper provides a barrier that is impervious to the environment, including but not limited to water and oxygen.

The individual dose package 250 according to the present invention is generally depicted in FIG. 2. In particular, FIG. 2 illustrates a perspective view of a single dose capsule 100 containing at least one pharmaceutical active ingredient 200 packaged and sealed within an outer wrapper 300. During use, a single dose capsule 100 may be removed from the outer wrapper 300 and placed in an automatic cooking machine.

In FIG. 1 is a perspective view of a single dose capsule 100 in accordance with the present invention. As shown in FIG. 1, a single-dose capsule 100 includes a cup 110 and a lid 120. Cup 110 has a bottom 150 and a side wall 160 extending upward from the bottom 150 to a rim 130 surrounding opening 170. Opening 170 leads to an interior space 140 defined by a side wall. wall 160 and bottom 150 of cup 110. Lid 120 may be attached to rim 130 of cup 110 to provide a permanent airtight seal. During the infusion cycle, the lid 120, bottom 150, and/or side wall 160 may be pierced or otherwise penetrated by the automatic brewer so that liquid, such as water, can enter cup 110 to be mixed with pharmaceutical active ingredient 200, and cooked the beverage can be dispensed from the cup 110.

Non-limiting examples of materials that may be included in the laminate of cup 110, lid 120, or outer wrap 300 include polystyrene, ethylene vinyl alcohol, polyethylene, biaxially oriented polyethylene terephthalate, high density polyethylene vinyl acetate, polyethylene, cyclic olefin copolymers, biaxially oriented polyamide, ionomer, polychlorotrifluoroethylene , polypropylene, polyester, amorphous polyethylene terephthalate, polyvinyl chloride, polyethylene, aluminum foil, polyethylene terephthalate glycol, polyethylene terephthalate glycol, polyethylene terephthalate of any density, polyethylene terephthalate of any density, polyethylene terephthalate of any density, polyethylene terephthalate with any orientation of their combination. Each layer of the cup 110, lid 120, or outer wrap 300 laminate may be adhesively attached to the adjacent layer.

In a preferred embodiment, cup 110, including bottom 150 and side wall 160, may be a multilayer structure made from any suitable materials that provide the desired barrier properties. Preferably, cup 110 includes at least an outer polystyrene layer, an ethylene vinyl alcohol (EVOH) middle layer, and an inner polyethylene layer.

During brewing in a standard automatic brew machine, cup 110 may be exposed to very hot liquid; thus, the cup 110 must retain its shape and securely hold the pharmaceutical active ingredient 200 in the interior 140 during the brewing process. Polystyrene can be used as the outer layer of cup 110 due to its high resistance to extreme temperatures. In addition, the automatic brewer may pierce the bottom 150 of the cup 110 to allow the prepared beverage to pass through the cup 110 and into the user's container for consumption. The polystyrene is brittle, that is, it breaks under stress without significant deformation, and allows the bottom 150 of the cup 110 to be easily and reliably pierced with any standard automatic cooking machine. The beverage prepared for consumption may be of any volume. In some embodiments, the prepared beverage may be 5 fl oz, 8 fl oz, or 10 fl oz. In the preferred embodiment, the volume of the prepared beverage is 8 fluid ounces.

The cup 110 may include an EVOH middle layer that protects the pharmaceutical active ingredient 200 from deterioration due to its low oxygen permeability. This increases the shelf life and reliability of the pharmaceutical active ingredient 200 stored in the interior 140 of the cup 110.

Pharmaceutical active ingredient 200 within interior space 140 of cup 110 may be any compound or composition that can be used to treat and/or prevent a disease and/or provide an overall improvement in the health and well-being of the wearer. Non-limiting examples of a pharmaceutical active ingredient include OTC actives, over-the-counter ingredients, vitamins, minerals, herbal materials, energy boosting materials, probiotics, fiber, prebiotics, decongestants, anti-inflammatory agents, cough suppressants, expectorants. , antihistamines, antitussives, painkillers, or any combination thereof.

Pharmaceutical active ingredient 200 may be acetaminophen, phenylephrine, dextromethorphan, diphenhydramine, ibuprofen, pseudoephedrine, guaifenesin, acetylcysteine, chlorpheniramine, cetirizine, levocetirizine, doxylamine succinate, loratadine, or any combination thereof. However, the present invention may be used with any pharmaceutical active ingredient or any combination of pharmaceutical active ingredients or combination of pharmaceutical active ingredients with one or more excipients. Pharmaceutical active ingredient 200 may be in any suitable form, including but not limited to powder, liquid, gel, or tablet.

In a preferred embodiment, the pharmaceutical 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.

In some embodiments, one or more pharmaceutical active ingredients may be present in an amount of from about 1 mg to about 2000 mg. In embodiments in which the pharmaceutical active ingredient 200 includes acetaminophen, it is present in an amount of from about 300 mg to about 1000 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 in which the pharmaceutically active ingredient 200 includes phenylephrine, it is present in an amount of from about 5 mg to about 30 mg. In a preferred embodiment, the phenylephrine is present in an amount of about 10 mg. In embodiments in which the pharmaceutical active ingredient 200 includes dextromethorphan, it is present in an amount of from about 5 mg to about 30 mg. In a preferred embodiment, dextromethorphan is present in an amount of about 20 mg. In embodiments in which the pharmaceutical active ingredient includes diphenhydramine, it is present in an amount of from about 5 mg to about 50 mg. In a preferred embodiment, diphenhydramine is present in an amount of about 25 mg.

Non-limiting examples of excipients include flavors, fillers, leavening agents, glidants, lubricants, antioxidants, sweeteners, colors, preservatives, lubricants, sorbents, or any combination thereof. Suitable flavors may include, for example, mint, menthol, peppermint, wintergreen, sweet mint, vanillin, caramel, chocolate, coffee, cinnamon, cloves, citrus, lemon, green tea, white tea, chamomile, lime, orange, grape, cherry , strawberry, fruit punch, honey, honey-lemon, other fruit flavors, or any combination thereof. Suitable excipients may include, for example, maltodextrin, silica, sodium citrate, tribasic calcium phosphate, anhydrous citric acid, sodium citrate, various grades of microcrystalline cellulose such as Avicel PH101, Avicel PH102 and Avicel PH2 00, corn starch, or any other combination thereof. . Suitable disintegrants may include, for example, sodium starch glycolate [Explotab], cross-linked polyvinylpyrrolidone, corn starch, gum arabic, croscarmellose sodium [Ac-di-sol], sodium carboxymethylcellulose, veegum, alginates, 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 and mineral oils, or any combination thereof. Suitable lubricants may include, for example, magnesium stearate, stearic acid and its pharmaceutically acceptable alkali metal salts, calcium stearate, sodium stearate, Cab-O-Sil, siloid, sodium lauryl sulfate, sodium chloride, magnesium lauryl sulfate, talc, or any other substances or their combination. 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, sodium propyl gallate, sodium sodium metabisulphite; or any combination thereof. Suitable sweeteners may include, for example, acesulfame potassium, aspartame, sucrose, or any combination thereof. Suitable colors may include, for example, FD&C. blue #1, FD&C red #40, D&C yellow #10, FD&C blue #1, FD&C red #40.

In a preferred embodiment, cover 120 may be a sandwich structure made from any suitable materials that provide the desired barrier properties. Cover 120 preferably includes at least an outer primer layer, a middle aluminum foil layer, and an inner sealant layer. Lid 120 can be securely and permanently attached to rim 130 of cup 110 with an inner sealant layer of lid 120 with pharmaceutical active ingredient 200 in interior space 140 of cup 110. The inner sealant layer can form an airtight seal between lid 120 and cup 110 that further protects the pharmaceutical active ingredient 200.

The total thickness of the cap 120 is from about 65 microns to about 82 microns. Preferably, the total thickness of the lid 120 is about 73.8 microns. The outer primer layer has a thickness of about 4 microns to about 9 microns. Preferably, the outer primer layer is about 6.8 microns thick. The middle layer of aluminum foil has a thickness of about 34 microns to about 40 microns. Preferably, the middle layer of aluminum foil is about 37 microns thick. The inner layer of sealant has a thickness of about 27 microns to about 33 microns. Preferably, the inner sealant layer is about 30 microns thick. The total thickness of the cover 120 after embossing is from about 100 microns to about 150 microns. Preferably, the total thickness of the cap 120 after embossing is about 125 microns. In general, the laminate structure of the lid 120 has a water vapor transmission rate of less than 0.05 g/100 inch ² /24 hours.

While cup 110 and lid 120, as described above, provide barrier properties, they may not be sufficient on their own to protect the sensitive pharmaceutical active ingredient 200 of the present invention. Thus, the single dose capsule 100 can be further packaged and sealed within the multilayer outer wrap 300 to provide additional protection against water, oxygen, and other environmental factors. The outer wrapper 300 may completely surround the single dose capsule 100, thereby sealing the single dose capsule 100 within the outer wrapper 300.

In particular, the outer wrap 300 provides the level of moisture and child protection required for pharmaceutical products. This is a higher standard than what is required by the manufacturers of disposable capsules used for tea, coffee or other similar beverages. The outer wrapper 300 may have a length of about 135 mm to about 140 mm and a width of about 80 mm to about 90 mm when laid flat on a surface without the single dose capsule 100 sealed inside. Preferably, the length of the outer wrapper 300 is about 135 mm and the width of the outer wrapper 300 is about 86.5 mm when laid flat on the surface without the single dose capsule 100 sealed inside. In addition, the outer wrap 300 may have a total thickness of from about 70 microns to about 100 microns. Preferably, the thickness of the outer wrap 300 is about 79.2 microns.

In FIG. 4 shows a cross section of the layers of the outer wrap 300 of the present invention. The outer wrap 300 can be made from any suitable materials that provide the desired barrier properties. In a preferred embodiment, the outer wrapper 300 includes a first layer which is a layer 410 of biaxially oriented polyethylene terephthalate (BoPET). The first layer 410 is a polyester film made from

polyethylene terephthalate stretched in two different directions to improve mechanical orientation. The first layer 410 provides several useful characteristics for the present invention, including, but not limited to, high tensile strength, durability, barrier properties, and transparency.

In addition, the first layer 410 of the outer wrap 300 has a thickness of about 20 microns to about 30 microns. Preferably, the first layer 410 is about 2-3 microns thick. The thickness of the first layer 410 increases the strength of the outer wrap 300 and makes it childproof. Usually the thickness of the BOPET layer used for similar products will be much less; however, such similar products will not be childproof and therefore cannot be used with pharmaceutical ingredients.

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

In a preferred embodiment, the outer wrap 300 includes a third layer, which is a layer 430 of aluminum foil. The third layer 430 has a thickness of about 7 microns to about 12 microns. Preferably, the thickness of the third layer 430 is about 8.9 microns. The third layer 430 allows the outer wrap 300 to be resistant to the passage of liquids and gases, including but not limited to water and oxygen. In particular, the molecular structure of aluminum foil creates a strong barrier that is ideal for use with pharmaceutical ingredients due to their sensitivity to environmental factors.

The third layer 430 eliminates exposure to liquids and gases; thereby prolonging the shelf life of the present invention and maintaining the quality and potency of the pharmaceutical active ingredient 200 contained in the cup 110. In addition, the third layer 430 is durable and strong while being lightweight and pliable. Therefore, it is ideal for packaging products of various shapes and sizes without losing its barrier properties.

In a preferred embodiment, the outer wrapper includes a fourth layer which is the ionomer layer 440. The fourth layer 440 has a thickness of 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 sealant and can be folded back on itself to create a seal around the single dose capsule 100.

As can be seen in FIG. 4, the first layer 410 may be the outermost layer of the outer wrap 300 on the outside. The second layer 420 may be provided between the first layer 410 and the third layer 430. The third layer 430 may be provided between the second layer 420 and the fourth layer 440. The fourth layer 440 may be the innermost layer of the outer wrap 300 on the seal or inner side.

In FIG. 3 is a perspective view of a single dose capsule 100 sealed within an outer wrapper 300. As shown in FIG. 3, the fourth layer 440 of one end of the overwrap 300 may be attached to the fourth layer 440 of the other end of the overwrap 300 to create a seal 310. The seal 310 provides an ideal seal to further protect the pharmaceutical active ingredient 200 contained in the single dose capsule 100.

The outer wrap 300 has a moisture vapor transmission rate of less than 0.005 g H ₂ O/100 inch ² /24 hours. Preferably, the outer wrap 300 has a moisture vapor transmission rate of less than 0.001 g H ₂ O/100 inch ² /2 4 hours. The moisture vapor transmission rate of the outer wrap was tested at 100°F and 90% relative humidity. In addition, the outer wrap 300 has an oxygen transmission rate of less than 0.005 cm ³ /100 inch ² /24 hours. Preferably, the outer wrap 300 has an oxygen transmission rate of less than 0.001 cm ³ /100 inch ² /24 hours. The oxygen transmission rate was tested at 73°F and 0% relative humidity. Thus, the outer wrapper 300 has excellent oxygen and moisture barrier properties ideal for pharmaceutical active ingredient 200 that can be used in individual dose packaging 250.

In addition, the outer wrapper 300 provides a child-resistant and tear-resistant package for the single dose capsule 100. The definition of tear resistant refers to a material that is capable of undergoing a reasonable level of stress and/or deformation without significant loss of integrity when subjected to forces that can be applied by a person. It is very important that the outer wrapper 300 be out of the reach of children in order to prevent children from ingesting potentially hazardous substances, such as the pharmaceutical active ingredient 200, which may be stored in the cup 110 of the present invention.

A standardized test for child safety in accordance with 16.CFR § 1700 Poison prevention packaging was made in accordance with the present invention, a failed test is defined as when a child opens the package or accesses the contents of the package. In one embodiment, the present invention may be childproof and may be assigned a score, which is referred to as an F value. The F value is the number of unit doses access to which is considered a failed test. The F value is determined based on the number of single doses that could cause serious injury or serious illness to a child, based on a child weighing 25 pounds (11.4 kg). In an embodiment of the present invention, the individual dose package 250 may be an F=1 package. In another embodiment, the individual dose package 250 of the present invention may be an F=3 package. In another embodiment, the individual dose package 250 of the present invention may be an F=4 package. In another embodiment, the individual dose package 250 of the present invention may be an F=5 package. In a preferred embodiment of the present invention, the individual dose package is an F=2 package.

A child safety test has shown that an individual dose package of 250 is more than 70% childproof when the package is an F=1, F=2, F=3, F=4, or F=5 package. In another embodiment, the individual dose package is more than 80% childproof when the package is F=1, F=2, F=3, F=4, or F=5. In a preferred embodiment, the individual dose package is 100% childproof when the package is an F=1, F=2, F=3, F=4, or F=5 package.

Additionally, a 16.CFR §1700 Poison Prevention Packaging test for senior adults was performed on the outer wrapper 300 of the present invention to ensure that adults with mobility problems could access the single dose capsule 100. In one embodiment, more than 90% of the elderly subjects successfully opened the outer wrap 300 using scissors or other suitable means. In a preferred embodiment, 100% of the elderly subjects successfully opened the outer wrap 300 with scissors or other suitable means.

Additional aspects of the present invention may be directed to methods for treating symptoms of a cold and/or flu, allergies, or other illnesses, comprising preparing a beverage as described herein and administering or consuming the prepared beverage. Additional aspects of the present invention may be directed to the use of a beverage prepared as described herein for the treatment of cold and/or flu symptoms, allergies or other diseases.

Example 1:

Example 1 describes the stability and suitable shelf life of the present invention. In particular, a stability study was conducted in an embodiment of the present invention in which the pharmaceutical active ingredient 200 is a combination of 650 mg of acetaminophen, 10 mg of phenylephrine and 20 mg of dextromethorphan.

The present invention has been tested under 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. %.

As shown in Tables 1-3 below, the study generally concluded that the evaluation data met specifications for all time points and storage conditions. In particular, the data obtained for the appearance of the granules and solution met the specifications for all time points and storage conditions. The data obtained for analysis for each active substance met the specifications for all time points and storage conditions with minimal changes over time. The data obtained for p-aminophenol showed no increase in degradation for all time points and storage conditions, with maximum results of less than 0.05%. Data generated for PHL021, PHL033, PHL052+PHL021-2, maximum unspecified degradation products (money) and total amount of degradation products, were within acceptable limits at each scheduled time and storage conditions. Data generated for DEX921, DEC922-1, undetermined degradation products, and maximum and total degradation products were within acceptable limits at each scheduled time and storage state. The microbiological purity of the present invention was assessed by total aerobic microbial count (TAMC), total combined yeast and mold count (TYMC), and the absence of specific E. coli microorganisms. The microbiological purity has been proven to meet the requirements of the finished product specification for all samples tested.

Based on the results noted above, the stability study concluded that there is a high level of confidence that the present invention is sufficiently reliable and that the individual dose capsule 100 can provide long-term stability of the pharmaceutical active ingredient 200 in the interior space 140 of the cup body 110.

Long term and accelerated stability data have demonstrated that the present invention is not adversely affected when packaged in a 100 single dose capsule. Therefore, the shelf life of the present invention is 24 months when packaged in a single dose capsule 100 of the present invention and stored below 25°C or equivalent.

A temperature cycling study was performed 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 for 12 hours at -20°C and then 12 hours at 10°C for a total of 5 cycles and 10 cycles. In addition, a high temperature static study was conducted at 50° C. for two weeks. The study concluded that the present invention is not sensitive to freezing, thawing and high temperatures.

Notes to table 1

Failed = test out of specification

NT = Not tested, ND = Not determined, NS = Not scaled

NMT = He more than

NR = No result

N/A = not applicable

Example 2:

Example 2 describes the stability and suitable shelf life of the present invention. In particular, a stability study was conducted in an embodiment of the present invention in which the pharmaceutical active ingredient 200 is a combination of 650 mg of acetaminophen, 10 mg of phenylephrine and 25 mg of diphenhydramine.

The present invention has been tested under 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 relative humidity. 75%.

As can be seen from Tables 4-6 below, the study as a whole concluded that the evaluation data met the specifications for all time points and storage conditions. In particular, the data obtained for the appearance of the granules and solution met the specifications for all time points and storage conditions. The data obtained for analysis for each active substance met the specifications for all time points and storage conditions with minimal changes over time. The data obtained for p-aminophenol showed no increase in degradation for all time points and storage conditions, with maximum results of less than 0.05%. Data generated for PHL021, PHL033, PHL052+PHL021-2, unspecified degradation products, and the maximum number and sum of total degradation products were within acceptable limits at each scheduled time and storage conditions. Data obtained for DPH, BEN, BPH degradation components, unspecified degradation components, and the maximum number and sum of all degradation products were within acceptable limits at each scheduled time and storage conditions. The microbiological purity of the present invention was assessed by the total number of aerobic microbes, the total number of combined yeasts and molds, and the absence of specific E. coli microorganisms. The microbiological purity has been proven to meet the requirements of the finished product specification for all samples tested.

Based on the results noted above, the stability study concluded that there is a high level of confidence that the present invention is sufficiently reliable and that a single serving capsule 100 can provide long-term stability of the pharmaceutical active ingredient 200 in the interior 140 of the cup body 110.

Long term, intermediate and accelerated stability data demonstrated that the present invention is not adversely affected when packaged in a 100 single dose capsule. Therefore, the shelf life of the present invention is 24 months when packaged in a single-dose capsule 100 of the present invention and stored below 25°C or equivalent.

A temperature cycling study was performed 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 for 12 hours at -20°C and then 12 hours at 10°C for a total of 5 cycles and 10 cycles. In addition, a high temperature static study was conducted at 50° C. for two weeks. The study concluded that the present invention is not sensitive to freezing, thawing and high temperatures.

Example 3:

Example 3 details the test method and the result of a child safety test conducted on the present invention to ensure that it complies with the Poison Prevention Packaging Act of 1970 Regulations and CFR Title 16: Part 1700.20. The testing method and test results are detailed below.

Child safety test method:

25 boys and 25 girls aged 42 months to 51 months inclusive were tested in pairs in two different test situations. 30% of children were aged 42-44 months, 40% of children were aged 45-48 months and 30% of children were aged 49-51 months. All children were prepared in advance and received detailed information.

First, a couple of children were placed in a room, handed identical packages, and the receptionist asked them to "please try to open this for me." Each child was then given 5 minutes to try to open their package. The administrator closely observed the children at all times during the test and did not influence the children in any way, either verbally or non-verbally. The children were given freedom of movement to work with the packages, i.e. children were allowed to get up, get down on the floor, knock or pry off the packaging. The children were also allowed to talk to each other about opening packages and watch each other try to open packages. If the child opened the package, the administrator said "thank you", took the package from the child and placed it in a place inaccessible to the child. The child was not asked to open the package a second time.

After 5 minutes, the administrator demonstrated how to open the package if any child did not open their package. A separate demo package was used for the administrator's demonstration. Before the demonstration, the children were asked to put their bags aside and were not allowed to continue trying to open them. During the demonstration, the administrator held the package about two feet away from the children and opened the package at normal speed, as if the administrator was about to use the contents. The administrator did not exaggerate any movements. The administrator also did not discuss or describe how to open the package.

After the demonstration, the administrator began a second 5-minute test period by instructing the children with the prompt "you are now trying to open your packages." If one or both children did not open their packages with their teeth during the first 5 minutes of the test period, the administrator instructed the children before the start of the second 5 minute test period that "you can use your teeth if you wish." The administrator then observed the children during a second 5-minute testing period or until both children opened their packages, whichever came first.

Child safety test results:

In the first 5 minutes of testing (before the demo), there were zero openings. Also, in the second 5-minute test period (after the demo), there were zero opens. This corresponds to an overall percentage of 0.00% for a full 10-minute test, which is within the tolerance of US 16CFR § 1700.20. Thus, the present invention meets the requirements of the child safety test according to US 16 CFR § 1700.20 as shown in Table 7.

These results are based on the assumption that the opening of a package is defined as the situation where a child gains access to 1 (or more) units packed in a package. This corresponds to a failure rate F=1. Table 7 below lists the number of package openings that will be considered a success, require continued testing, or will be considered a failure during the first 5 minutes of testing and the full 10 minute test in accordance with US 16 CFR § 1700.20.

Example 4:

Example 4 details the test method and test result for a geriatric adult conducted in accordance with the present invention to ensure compliance with the Poison Prevention Packaging Act of 1970 Regulations and Code of Federal Regulations Title 16: Part 1700.20. The testing method and test results are detailed below.

Adult testing method:

The test was conducted with 100 participants, of which 70% were women and 30% were men. 25% of the participants were between the ages of 50 and 54, 25% of the participants were between the ages of 55 and 59, and 50% of the participants were between the ages of 60 and 70. Each participant participated in the test individually and was not in the presence of other participants or strangers. The test was conducted in a well-lit and distraction-free room.

The administrator began the first 5-minute test period by instructing the participant to open the provided package in accordance with the instructions on the package. The participant was given 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 removed all test materials from the participant.

The administrator then began the second trial period by providing the participant with another identical package. The second test period lasted 1 minute. The administrator instructed the participant that it was an identical package and reopen it as instructed. The administrator also informed the participants that in order to open the package, they must cut the seals at the ends with scissors. After the second testing period, or when the participant opened the package, whichever happened first, the administrator removed all test materials from the participant.

Test results for older adults:

16 CFR § 17 00.2 0 allows a 10% failure rate. The results of a test for elderly adults, carried out in accordance with the described procedure, show that during the first period of testing, zero unsuccessful attempts to open the package were recorded. During the second testing period, zero unsuccessful attempts to open the package were recorded. This corresponds to an overall percentage of 0.00% for a full 10-minute test, which is within the tolerance of US 16 CFR § 1700.20. Thus, the present invention meets the adult testing requirements of 16 CFR § 1700.20.

Claims (37)

1. Individual dose package for use with an automatic brewer, containing: single dose capsule comprising: a cup having a bottom and a side wall extending from the bottom to a rim surrounding the opening, wherein the space between the bottom and the side wall defines the interior space, at least one pharmaceutical active ingredient located in the interior of the cup, and a lid attached to the rim of the cup, thereby closing the opening and keeping at least one pharmaceutical active ingredient in the interior of the cup; And an outer wrapper enclosing the entire single-dose capsule and sealing the single-dose capsule, wherein the outer wrapper creates an impermeable barrier preventing the penetration of liquids and gases, wherein the outer wrapper is a multilayer structure, including the first layer, which is a biaxially oriented polyethylene terephthalate layer, the second layer, which is a polyethylene layer, the third layer, which is an aluminum foil layer, and the fourth layer, which is an ionomer layer, while The outer wrap is 100% childproof with zero openings over a 10 minute period. 2. The unit dose package of claim 1, wherein at least one pharmaceutically active ingredient is acetaminophen, phenylephrine, dextromethorphan, diphenhydramine, ibuprofen, pseudoephedrine, guaifenesin, acetylcysteine, chlorpheniramine, cetirizine, levocetirizamine, doxylaminesuccine, or a combination thereof. 3. The unit dose package according to claim 2, wherein at least one pharmaceutically active ingredient is acetaminophen. 4. The individual dose package of claim 2, wherein the at least one pharmaceutical active ingredient is a combination of acetaminophen, phenylephrine, and dextromethorphan. 5. The unit dose package of claim 2 wherein at least one pharmaceutical active ingredient is a combination of acetaminophen, phenylephrine and diphenhydramine. 6. The unit dose package of claim 2 wherein at least one pharmaceutical active ingredient is a combination of guaifenesin and dextromethorphan. 7. The individual dose package of claim 1 wherein the outer wrapper has a thickness of 70-100 microns. 8. The individual dose package of claim 1, wherein the first layer of the outer wrap has a thickness of 20-30 microns. 9. The individual dose package of claim 1, wherein the second layer of the outer wrap has a thickness of 10-20 microns. 10. The individual dose package of claim 1, wherein the third layer of the outer wrap has a thickness of 7-12 microns. 11. The individual dose package of claim 1, wherein the fourth layer of the outer wrap has a thickness of 30-40 microns. 12. The individual dose package of claim 1, wherein the outer wrapper has a moisture vapor transmission rate of less than 0.001 g H ₂ O/100 in ² /24 hours. 13. The individual dose package of claim 1, wherein the outer wrapper has an oxygen transmission rate of less than 0.001 cm ³ /100 inches ² /24 hours. 14. The individual dose package of claim 1, wherein the outer wrapper has a length of 130-140 mm and a width of 80-90 mm in a horizontal position. 15. The individual dose package of claim 1, wherein the fourth layer of one end of the overwrap is folded and adhered to the fourth layer of the other end of the overwrap to form a sealed portion and seal the single dose capsule within the overwrap. 16. The individual dose package of claim 1 that is 100% accessible to older adults with zero failed openings over a 10 minute period. 17. A multilayer outer wrapper containing: the first layer, which is a biaxially oriented layer of polyethylene terephthalate; the second layer, which is a layer of polyethylene; the third layer, which is a layer of aluminum foil; and a fourth layer, which is an ionomer layer, while the outer wrap is childproof and creates an impermeable barrier that prevents the penetration of liquids and gases, while The outer wrap is 100% childproof with zero openings over a 10 minute period. 18. The multilayer overwrap according to claim 17, wherein the first layer of the multilayer overwrap has a thickness of 20-30 microns. 19. The multilayer overwrap according to claim 17, wherein the second layer of the multilayer overwrap has a thickness of 10-20 microns. 20. The multilayer overwrap according to claim 17, wherein the third layer of the multilayer overwrap has a thickness of 7-12 microns. 21. The multilayer overwrap according to claim 17, wherein the fourth layer of the multilayer overwrap has a thickness of 30-40 microns. 22. A multilayer overwrap according to claim 17, having a water vapor transmission rate of less than 0.001 g H ₂ O/100 ^{in 2} /24 hours. 23. A multilayer overwrap according to claim 17 having an oxygen transmission rate of less than 0.001 cm ³ /100 inches ² /24 hours. 24. The multilayer outer wrap of claim 17, which is 100% accessible to older adults with zero failed openings over a 10 minute period.