INGESTIBLE PLANT SOURCE PILL AND METHOD

FIELD

The present disclosure relates to pills, and more generally to an ingestible plant source pill for administering a dose of active ingredients.

BACKGROUND

[0001] Many medicinal ingredients of therapeutic efficacy for various conditions or ailments may be found in plant sources, including the cannabis plant. In some cases, delivering these therapeutic medicinal ingredients from the plant source may involve subjecting the plant source material to combustion, or heating the plant source material for delivery of vapor via inhalation. However, these delivery methods are relatively slow, and may require a patient to spend a significant amount of time to complete a dose. While this may be acceptable in some cases, if a patient lacks the necessary time, a dose may only partially completed or perhaps may be skipped altogether, possibly reducing the efficacy and likelihood of successful treatment of the condition for which the therapeutic plant source material was prescribed.

[0002] What is therefore needed is a more convenient delivery method that overcomes at least some of these limitations.

SUMMARY

[0003] The present disclosure relates to an ingestible therapeutic plant source pill for administering a dose of one or more active ingredients. The pill may be a tablet, capsule or a hybrid variant such as a caplet, suitable for delivering an oral dosage of the therapeutic plant source pill.

[0004] In an aspect, the ingestible therapeutic plant source pill comprises a tablet formed by compressing loose plant source material that has been processed into a compressible state. This processing may involve drying, shredding, grinding, and mixing the plant source material with one or more base materials which may help the loose plant source material and any base material to bind together during compression, helping the resulting compressed tablet retain its shape. [0005] As the tablet must be ingestible orally, the size of the tablet should be of a suitable size for swallowing, and to allow for flexibility in prescribing dosages by taking multiple tablets as may be necessary. In an embodiment, each tablet preferably has a maximum dimension of 22mm in the largest dimension.

[0006] The tablets may also include a scored center line to allow the tablet to be cut in half, as may be necessary to comply with the prescribed dosage. Each tablet may also be coated with a smooth coating which allows the tablet to be swallowed more easily.

[0007] In another aspect, the ingestible therapeutic plant source pill comprises a capsule containing plant source material in loose form such as dried and finely shredded pieces, formed granular pellets, or a finely ground powder. The amount of shredding, the granularity of the pellets, or the fineness of the powder may be selected to control digestibility and the rate of absorption of the plant source material and its active ingredient(s) in a patient's digestive tract.

[0008] In another aspect, the ingestible therapeutic plant source pill comprises a liquid gel capsule containing plant source material processed into a liquid form.

[0009] In another aspect, the plant source material may be processed to reduce the bulk of non-therapeutic ingredients prior to being compressed into a tablet, or into granular pellets or a power for encapsulation. The plant source material may also be processed to obtain one or more extracts of therapeutic ingredients for inclusion in a tablet or capsule.

[0010] In another aspect, the ingestible therapeutic plant source pill may be distinguished by size, shape, or color to identify the variant of the plant material, or to identify a dose. The ingestible therapeutic plant source pill may be packaged in a bottle, or alternatively may be individually packaged in blister packaging to extend the shelf life of each pill. Sealing in a blister pack may strictly control the amount of desired humidity in the tablet, in order to maintain freshness and longevity of the ingredients.

[0011] In an embodiment, the ingestible therapeutic plant source pill may include various flavoring agents which may provide a pleasant taste as the pill is put into the mouth of a patient to be swallowed.

[0012] In this respect, before explaining at least one embodiment of the system and method of the present disclosure in detail, it is to be understood that the present system and method is not limited in its application to the details of construction and to the arrangements of the components set forth in the following description or illustrated in the drawings. The present system and method is capable of other embodiments and of being practiced and carried out in various ways. Also, it is to be understood that the phraseology and terminology employed herein are for the purpose of description and should not be regarded as limiting.

BRIEF DESCRIPTION OF THE DRAWINGS

[0013] FIG. 1 shows ingestible therapeutic plant source pills in accordance with various embodiments.

[0014] FIG. 2 shows an illustrative example of a pill in accordance with an embodiment sealed within a blister pack.

[0015] FIG. 3 shows an illustrative process for preparing various forms of ingestible plant source pills.

DETAILED DESCRIPTION

[0016] As noted above, the present disclosure relates to pills, and more generally to an ingestible therapeutic plant source pill suitable for delivering an oral dosage of active ingredients of a therapeutic plant source.

[0017] In an embodiment, the active ingredients are mixed with one or more of binders, fillers, flavoring, bulking agents, preservatives and antioxidants. The ingredients may be dried, milled, blended, compressed and granulated to achieve the desired properties before they are manufactured as a final formulation. Tablets and capsules are very common oral dosage forms, as are hybrids such as caplets and gel caps. Another common form is sterile liquids for injection or ophthalmic application.

[0018] When cannabis is ingested, one of its main active ingredients, THC, is metabolized by a patient's liver, which converts the THC to 11 -hydroxy-THC. This active metabolite has been found to readily cross the blood-brain barrier, resulting in a more potent effect of the active ingredient on the patient. In comparison, inhaled cannabis undergoes a different metabolic process, and rather than passing through a patient's stomach and then his/her liver, inhaled cannabis (e.g. its active ingredient THC) travels directly to the patient's brain. Consequently, inhalation of vaporized cannabis from smoking or a vaporizer works faster than ingested cannabis, but its effect on the patient also diminishes more quickly than ingested THC.

[0019] The effects of inhaled cannabis via smoking or vaporizing tend to peak within about the first 10 minutes of inhalation, and rapidly dissipate over the next 30 to 60 minutes. In contrast, metabolization by the liver can take anywhere from about 30 minutes to 2 hours before the effects of ingestion of cannabis become apparent, and this can last several hours, significantly longer than inhaled cannabis. As large dosages of active ingredient, THC, may have a negative effect on the patient, the dosages should initially be small, and spaced apart sufficiently such that the effects on a patient are known before any incremental increase or decrease in the dosage is prescribed.

[0020] While the resulting effects of ingesting cannabis on a patient may be relatively strong when compared to inhaled cannabis, ingestion actually delivers a smaller concentration of cannabinoids to the bloodstream. On average, ingesting edibles may introduce only about 10 to 20 percent of the total ingested THC and other cannabinoids to the blood plasma, whereas inhaled cannabis may introduce closer to 50 or 60 percent of the total THC in the cannabis material.

[0021] Determining the THC content within an ingestible therapeutic plant source pill may sometimes be difficult, and consequently patients may sometimes underestimate or overestimate the dose they have already received. Inhaled cannabis, with its instantaneous effects, allows a patient to gradually increase a dose as needed. However, as noted, this may not be a practical alternative.

[0022] As an illustrative example, in the State of Colorado, 10 milligrams of THC (or

CBD) is considered a "standard" dose that normally delivers relatively mild effects to a patient.

[0023] In comparison, a 1 OOmg edible cannabis product is potentially much more potent, and therefore should be split into several doses over time. Therefore, the ingestible therapeutic plant source pills of the present invention should allow for flexibility in prescribing smaller doses of cannabis and its active ingredients. [0024] In a preferred embodiment, each batch of plant source material processed in preparation for producing a pill such as by using MAP (Modified Atmosphere Packaging) techniques may undergo potency testing.

[0025] Advantageously, by controlling the amount of the active ingredients in a given pill, which can be readily replicated, the ingestible therapeutic plant source pill of the present disclosure allows significantly greater control over standardized dosing of active ingredients in the cannabis plant and other plant sources, and better control over the desired therapeutic effect on the condition being treated.

[0026] Furthermore, as ingestion completely avoids potentially harmful by-products of combustion, as is present in smoking, ingestion may be a preferred alternative for dosage for some patients. Vaporization is another health-conscious alternative commonly recommended, but ingestible pills can oftentimes provide longer lasting relief for chronic symptoms such as pain, often making them a preferred choice for patients.

[0027] Various illustrative embodiments will now be described in more detail with reference to the figures.

Tablets

[0028] Referring to FIG. 1(a), shown is an ingestible tablet in accordance with an illustrative embodiment. Different types of tablets include sublingual tablets, buccal tablets, melts, and oro-dispersible tablets, for example.

[0029] Sublingual tablets are designed to be dissolved under the tongue, are rapidly absorbed through the tongue and therefore work quickly. This is why some tablets for the treatment of angina pain and others for general pain are formulated in this manner. The sublingual (under the tongue) or oromucosal (in the oral cavity) delivery method of an oil or tincture provides another rapid onset of action as the medication is readily absorbed into the blood system.

[0030] Buccal tablets are intended to be placed on the gum or in the cheek to allow the drug to be absorbed. Because the medicine can be held for a longer period of time on the gum, medicines which need to be released at a slower rate than sub-lingual tablets can be given via this route. This route is used for anti-nausea drugs and nicotine replacement gums. Anti-nausea medicines are particularly suitable for buccal administration as the nausea itself can cause swallowed tablets to be vomited and therefore rendered ineffective.

[0031] Melt tablets are placed on the tongue and are designed to dissolve directly in the mouth's saliva. The contents are then swallowed with saliva and consequently water does not have to be administered with these medicines. This is particularly useful in patients who are at risk of aspiration and therefore unable to swallow tablets with water concurrently.

[0032] Oro-dispersible tablets are similar to melts and are designed to disperse in the mouth and to be washed down with saliva. As with sub-lingual, buccal and melts, oro-dispersible products require an adequate amount of saliva production. Some oro-dispersible tablets consist of coated granules and therefore it is not appropriate to crush the oro-dispersible product prior to dispersion.

[0033] In an aspect, the ingestible therapeutic plant source pill comprises a tablet formed by compressing plant source material that has been processed into a compressible state. This processing may involve drying, shredding, grinding, and mixing the plant source with or without one or more base materials which may help the loose plant source material and any base material to bind together during compression, helping the resulting compressed tablet retain its shape.

[0034] As an illustrative example, in an embodiment, the plant source material may be the hemp plant which is composed of approximately 20% lignin, a polymer in plants that provides rigidity. In another embodiment, the plant source material may be the cannabis plant.

[0035] In an embodiment, as the plant source material is compressed, it is heated by frictional forces. The lignins (contained in all woody-cellulose materials) begin to flow and act as a natural glue to bind the compressed plant source materials. Sticky trichomes, which are present predominantly in flowers, will also serve to bind the material, possibly reducing the total pressure needed to form the tablets. When the compressed material exits the compression machine, the lignins cool, solidify and hold the plant source material together to form the tablet.

[0036] In experimentation, it has been found that hydraulic presses will generally produce compressed tablets which are suitably dense and of sufficient hardness to retain their rigid shape. However, it will be appreciated that other types of presses (e.g. mechanical presses) may also be used if they can provide the sufficient compression force and desired ambient parameters.

[0037] During compression, temperatures rise sufficiently to make the raw material liberate various adhesives that will assist in keeping the particles together in the compressed shape. However, to make this process successful, the moisture content for most hemp based material is preferably around 10 - 12%, although the range may be somewhat broader in the range of 8 - 14% and still provide good performance.

[0038] In a preferred embodiment, tablets are formed, using special dies. High pressures

(e.g. 10 tons) and temperatures (200 °F/93°C) are generated in this process, which softens components of the hemp (the lignin) and binds the material in the tablet together. No additional adhesives are required.

[0039] To form a tablet, the granulated material must be metered into a cavity formed by two punches and a die. A tablet is formed by the combined pressing action of two punches and a die. In the first step of a typical operation, the bottom punch is lowered in the die creating a cavity into which the ground material is fed. The exact depth of the lower punch can be precisely controlled to meter the amount of material that fills the cavity. The excess is scraped from the top of the die, and the lower punch is drawn down and temporarily covered to prevent spillage. Then, the upper punch is brought down into contact with the material as the cover is removed. The force of compression is delivered by high pressure compression rolls which fuse the ground material together into a hard tablet. After compression, the lower punch is raised to eject the tablet.

[0040] While the tablet should be sized small enough to be swallowed, it will be appreciated that the amount of plant source material and the dimensions of the tablet are provided by way of illustration only, and are not meant to be limiting.

[0041] There are generally two types of tablet presses: single-punch and rotary tablet presses. Most high speed tablet presses take the form of a rotating turret that holds any number of punches. As they rotate around the turret, the punches come into contact with cams which control the punch's vertical position. Punches and dies are usually custom made for each application, and can be made in a wide variety of sizes, shapes, and can be customized with manufacturer codes and scoring lines to make tablets easier to break. Depending on tablet size, shape, material, and press configuration, a typical modern press can produce from 250,000 to over 1,000,000 tablets an hour. Consequently, an automated process for compressing tablets may produce a large quantity of ingestible tablets cost effectively.

[0042] In the tablet pressing process, the main guideline is to ensure that the appropriate amount of active ingredient is in each tablet. Hence, all the ingredients should be well-mixed. If a sufficiently homogenous mix of the components cannot be obtained with simple blending processes, the ingredients must be granulated prior to compression to assure an even distribution of the active compound in the final tablet. Two basic techniques are used to granulate powders for compression into a tablet: wet granulation and dry granulation.

[0043] Wet granulation is a process of using a liquid binder to lightly agglomerate the powder mixture. The amount of liquid has to be properly controlled, as over-wetting will cause the granules to be too hard and under-wetting will cause them to be too soft and friable. Aqueous solutions have the advantage of being safer to deal with than solvent-based systems but may not be suitable for drugs which are degraded by hydrolysis. The active ingredient and excipients are weighed and mixed.

[0044] The wet granulate is prepared by adding the liquid binder-adhesive to the powder blend and mixing thoroughly. Examples of binders/adhesives include aqueous preparations of cornstarch, natural gums such as acacia, cellulose derivatives such as methyl cellulose, gelatin, and povidone.

[0045] A conventional tray-dryer or fluid-bed dryer are most commonly used. After the granules are dried, they are passed through a screen of smaller size than the one used for the wet mass to create granules of uniform size.

[0046] Low shear wet granulation processes use very simple mixing equipment, and can take a considerable time to achieve a uniformly mixed state. High shear wet granulation processes use equipment that mixes the powder and liquid at a very fast rate, and thus speeds up the manufacturing process. Fluid bed granulation is a multiple-step wet granulation process performed in the same vessel to pre-heat, granulate, and dry the powders. It is used because it allows close control of the granulation process. [0047] Dry granulation processes create granules by light compaction of the powder blend under low pressures. The compacts so-formed are broken up gently to produce granules (agglomerates). This process is often used when the product to be granulated is sensitive to moisture and heat. Dry granulation can be conducted on a tablet press using slugging tooling or on a roll press called a roller compactor. Dry granulation equipment offers a wide range of pressures to attain proper densifi cation and granule formation. Dry granulation is simpler than wet granulation, therefore the cost is reduced. However, dry granulation often produces a higher percentage of fine granules, which can compromise the quality or create yield problems for the tablet. Dry granulation requires drugs or excipients with cohesive properties, and a 'dry binder' may need to be added to the formulation to facilitate the formation of granules.

[0048] After granulation, a final lubrication step is used to ensure that the tableting blend does not stick to the equipment during the tableting process. This usually involves low shear blending of the granules with a powdered lubricant, such as magnesium stearate or stearic acid.

Capsules

[0049] Referring to FIG. 1(b), in an alternative embodiment, the ingestible therapeutic plant source pill may be a capsule containing loose plant source material. The loose plant source material may be, for example, shredded leaves of the cannabis plant, a powder obtained by grinding a cannabis plant, or granular pellets formed from further processing of the cannabis plant.

[0050] Mechanical separation methods use physical action to remove the trichomes from the plant, such as sieving through a screen by hand or in motorized tumblers. This technique is known as "drysifting". The resulting powder, referred to as "kief or "drysift", is compressed with the aid of heat into blocks of hashish; if pure, the kief will become gooey and pliable. When a high level of pure THC is present, the end product will be almost transparent and will start to melt at the point of human contact. Ice-water separation is another mechanical method of isolating trichomes. The clarity of the final product determines quality of the final product. Nowadays, new techniques have been developed, such as heat and pressure separations, static- electricity sieving or acoustical dry sieving.

[0051] As an illustrative example, a process for forming a capsule of loose plant source material may involve the steps of 1) preliminary identification and testing for potency; 2) pre- blending; 3) wet granulation; 4) weighing and mixing; 5) encapsulating; 6) polishing; and 7) inspection.

[0052] The cannabis intended for use must first be tested for identity and potency, and for possible bacterial contamination as well.

[0053] If the ingredients are not finely granulated, they will be run through a mill and ground. Some may be pre-blended with a filler ingredient such as microcrystalline cellulose or malto-dextrin, because this produces a more even granule which aids further processing steps. Laboratory technicians may run test batches when working with new ingredients and determine if pre-blending is necessary.

[0054] Particle size is extremely important in determining how well the formula will run through the encapsulating machine. A wet granulation step may be necessary. In wet granulation, the fine cannabis powder is mixed with a variety of cellulose particles, then wetted. The mixture is then dried in a dryer. After drying, the formula may be in chunks as large as a dime. These chunks are sized by being run through a mill. The mill forces the chunks through a small hole of the desired diameter of the granule. These granules can then be weighed and mixed.

[0055] When all the cannabis ingredients are ready, a worker takes them to the weigh station and weighs them out on a scale. The required weights for each ingredient in the batch are listed on a formula batch record. After weighing, all the ingredients go into a mixer. The ingredients spend from 15 to 30 minutes in the mixer. At this point, samples are taken from different sides of the mixer and checked in the laboratory. The lab technicians verify that all the ingredients are distributed in the same proportion throughout the mix. After mixing is complete, the cannabis is taken to the encapsulating machine.

[0056] If the lot in the mixer has been approved, the mixture is dumped into the encapsulating machine hopper. The cannabis mixture flows through one hopper, and another hopper holds whole gelatin capsules. The capsules are broken into halves by the machine. The bottom half of the capsule falls through a funnel into a rotating dosing dish. Then the machine measures a precise amount of the powdered cannabis mixture into each open capsule half. Tamping pins push the powder down. Then the top halves of the capsules are pushed down onto the filled bottoms. [0057] The filled cannabis capsules are next run through a polishing machine. The cannabis capsules are circulated on a belt through a series of soft brushes. Any excess dust or cannabis powder is removed from the exterior of the capsules by the brushes. The polished capsules are then poured onto an inspection table.

[0058] The inspection table has a belt of rotating rods. The cannabis capsules fall in the grooves between the rods, and the cannabis capsules rotates as the rods turn. Thus, all sides of the cannabis capsules are visible for the inspector to see. The inspector removes any capsules that are too long, split, dimpled, or otherwise imperfect. The cannabis capsules that pass inspection are then taken over to the packaging area.

Liquid Gel Capsule

[0059] Cannabis can also be strained in a solvent (i.e.: isopropyl alcohol, ether, butane, propane, and C0 ₂ ) to form a viscous liquid which is then strained and the solvent is evaporated to yield hash oil. Hash oil (also known as hashish oil, BHO, wax, shatter, crumble, honey oil dabs, or budder) is a form of cannabis. It is a resinous matrix of cannabinoids obtained from the Cannabis plant by solvent extraction, formed into a hardened or viscous mass. Hash oil is a cannabis product obtained by separating resins from cannabis plant matter by solvent extraction.

[0060] In an embodiment, hash oil could also be put in to a capsule form or made into a suppository. Hashish, is a cannabis product composed of compressed or purified preparations of stalked resin glands, called trichomes. It contains the same active ingredients— such as tetrahydrocannabinol (THC) and other cannabinoids— but often in higher concentrations than unsifted buds or leaves.

[0061] It is possible to extract pure THC, CBD or any other cannabinoids individually from the cannabis and then to blend them in any ratio desired. Any terpenes could also be added to the blend. This blend of active ingredients could then be mixed with an excipient and formed into a suppository, tablet, capsule and variants like caplets...and patented.

[0062] Hashish may be solid or resinous depending on the preparation; pressed hashish is usually solid, whereas water-purified hashish— often called "bubble melt hash"— is often a pastelike substance with varying hardness and pliability, its color most commonly light to dark brown can vary to see-through glass varying toward yellow/tan, black or red. This all depends on the process and amount of solvent left over.

[0063] Hashish is made from cannabinoid-rich glandular hairs known as trichomes, as well as varying amounts of cannabis flower and leaf fragments. The flowers of a mature female plant contain the most trichomes, though trichomes are also found on other parts of the plant. Certain strains of cannabis are cultivated specifically for their ability to produce large amounts of trichomes. The resin reservoirs of the trichomes, are separated from the plant through various methods.

[0064] Hash oil can be the most potent of the main cannabis products because of its high level of psychoactive compound per its volume, which can vary depending on the plant's mix of essential oils and psychoactive compounds. Butane and supercritical carbon dioxide hash oil have become popular in recent years.

[0065] An excipient is a natural or synthetic substance formulated alongside the active ingredient of a medication included for the purpose of bulking-up formulations that contain potent active ingredients (thus often referred to as "bulking agents," "fillers," or "diluents"), or to confer a therapeutic enhancement on the active ingredient in the final dosage form, such as facilitating drug absorption or solubility. A wide variety of binders may be used, some common ones including lactose, dibasic calcium phosphate, sucrose, corn (maize) starch, microcrystalline cellulose, povidone polyvinylpyrrolidone and modified cellulose (for example hydroxypropyl methylcellulose and hydroxyethylcellulose).

[0066] Often, an ingredient is also needed to act as a disintegrant to aid tablet dispersion once swallowed, releasing the API for absorption. Some binders, such as starch and cellulose, are also excellent disintegrants.

[0067] Excipients can also be useful in the manufacturing process, to aid in the handling of the active substance concerned such as by facilitating powder flowability or non-stick properties, in addition to aiding in vitro stability such as prevention of denaturation over the expected shelf life. The selection of appropriate excipients also depends upon the route of administration and the dosage form, as well as the active ingredient and other factors. Though excipients were at one time considered to be "inactive" ingredients, they are now understood to be "a key determinant of dosage form performance". Pill Size

[0068] As the tablet must be ingestible orally, the size of the tablet should be of a suitable size for swallowing, and to allow for flexibility in prescribing dosages by taking multiple tablets as may be necessary. Generally, the largest dimension of a tablet should not exceed 22 mm and that capsules should not exceed standard 00 size. As an illustrative example, Table A, below, shows some common sizes for two piece capsules.

Standard sizes of two piece capsules (Domestic Supplier)

Table A

[0069] The tablets may also include a scored center line to allow the tablet to be cut in half, as may be necessary to comply with the prescribed dosage. Each tablet may also be coated with a smooth coating which allows the tablet to be swallowed more easily.

Testing Potency

[0070] There are presently a number of major testing methods for testing potency of canabinoids in a drug formulation:

[0071] GC - Gas Chromatography- is a common type of chromatography used in analytical chemistry for separating and analyzing compounds that can be vaporized without decomposition. Typical uses of GC include testing the purity of a particular substance, or separating the different components of a mixture (the relative amounts of such components can also be determined). In some situations, GC may help in identifying a compound. In preparative chromatography, GC can be used to prepare pure compounds from a mixture. GC is perhaps the most common method of chemical analysis in use in the world today. In GC, the sample under study is vaporized and then pushed by a mix of gases through a long, thin, coated tube, not unlike a hollow fiber optic line up to 60 feet long. The different cannabinoids separate from each other as they travel, and are measured at the far end, usually by a detector known as a FID that burns whatever comes out of the tube and looks for the products of combustion. (One alternative detector is a mass spectrometer, much more sensitive but far more expensive and difficult to operate.) The response from the detector is compared to the response to a "reference sample" that contains a known amount of specific cannabinoids in it. Comparing the timing and size of the signals from the detector allows the analyst to calculate the amount of targeted cannabinoids in the unknown sample. GC is well suited for measuring small quantities of cannabinoids. For cannabinoid testing, its main weakness is that, because the sample is vaporized at high temperatures when it enters the machine, it cannot distinguish THC from THC-A in a sample unless significant additional processing is done. This makes the technology impractical for testing infused products. The coated tubes cost several hundred dollars apiece and are used for hundreds or thousands of tests before replacement, leading to problems from contamination and degradation of the column.

[0072] HPLC - High Performance Liquid Chromatography (HPLC; formerly referred to as high-pressure liquid chromatography), is a technique in analytical chemistry used to separate the components in a mixture, to identify each component, and to quantify each component. It relies on pumps to pass a pressurized liquid solvent containing the sample mixture through a column filled with a solid adsorbent material. Each component in the sample interacts slightly differently with the adsorbent material, causing different flow rates for the different components and leading to the separation of the components as they flow out the column. In HPLC, the sample is pushed by liquid solvents through a short tube packed with silica particles. The separated cannabinoids are measured at the far end, usually by monitoring the output with a beam of ultraviolet light. The main drawback of this method is that the UV detector responds to many substances in addition to cannabinoids, leading to interference, and has significantly different responses to different cannabinoids, requiring calibration for each separate cannabinoid. As with GC, the columns must be re-used many times, leading to contamination and degradation problems. Finally, HPLC equipment tends to be temperamental, with significant downtime for repair and maintenance.

[0073] HPLC differs from traditional ("low pressure") liquid chromatography as operational pressures are significantly higher (50-350 bar), compared to ordinary liquid chromatography which typically relies on gravity to pass the mobile phase through the column.

[0074] High-Performance Thin-Layer Chromatography (HPTLC) is the most advanced form of TLC (See below) and comprises the use of chromatographic layers of utmost separation efficiency and the employment of state-of-the-art instrumentation for all steps in the procedure: precise sample application, standardized reproducible chromatogram development and software controlled evaluation. HPTLC is an entire concept that includes a widely standardized methodology based on scientific facts as well as the use of validated methods for qualitative and quantitative analysis. In HPTLC, the sample is "spotted" onto a disposable, silica-coated plate. Liquid solvents are then run across the plate, separating out the cannabinoids. The plates are treated with chemicals and scanned at a particular frequency to reveal the cannabinoids. HPTLC particularly lends itself to the analysis of complex mixtures, such as plant or food samples, as detection can be limited to specific groups of substances - in this case, cannabinoids - and the use of disposable plates means that no residues accumulate from one test to the next. The main limitation of HPTLC is that it is not as sensitive to minute levels of cannabinoids as GC or HPLC. However, even the most dilute medical marijuana products such as sodas and drinks contain enough cannabinoids to be accurately measured with HPTLC.

[0075] TLC - Thin-Layer Chromatography (TLC) is a simple, flexible and cost efficient separation technique for both qualitative and quantitative analysis, enabling simultaneous analysis of many substances with minimal time requirement. Thin-layer chromatography can be used to monitor the progress of a reaction, identify compounds present in a given mixture, and determine the purity of a substance. Specific examples of these applications include: analyzing ceramides and fatty acids, detection of pesticides or insecticides in food and water, analyzing the dye composition of fibers in forensics, assaying the radiochemical purity of radiopharmaceuticals, or identification of medicinal plants and their constituents.

Coatings [0076] In another embodiment, the ingestible therapeutic plant source pill may be coated to make swallowing the pill easier, and to provide a barrier to objectionable taste or odor. For example, the pill may be coated with a colored or uncolored sugar layer. The coating may be water soluble and quickly dissolve after swallowing. The sugar coat may also act to protect the enclosed therapeutic ingredients from the environment. The sugar coat may also enhance the appearance of the pill, and permit imprinting of manufacturer's information. Thus, sugar coating may provide a combination of insulation, taste masking, smoothing of the pill core, coloring, and a modified release of the active ingredient. However, sugar coating does increase the size and weight of the pills, and thus the shipping costs.

[0077] Another type of coating is a film coating, which is more favored over sugar coating. Film coating is deposition of a thin film of polymer surrounding the tablet core. Conventional pan equipments may be used but now a day's more sophisticated equipments are employed to have a high degree of automation and coating time. The polymer is solubilised into solvent. Other additives like plasticizers and pigments are added. Resulting solution is sprayed onto a rotated tablet bed. The drying conditions cause removal of the solvent, giving thin deposition of coating material around each tablet core. Flavors, sweeteners, surfactants, antioxidants, antimicrobials, etc. may be incorporated into the coating solution.

[0078] Table B, below, summarizes some of the features of these two types of coating:

FEATURES FILM COATING SUGAR COATING

Tablet: Retain contour of original core

Rounded with high degree of Appearance Usually not as shiny as sugar

polish

coat type

Weight increase because of

30-50%

coating material 2-3%

Not possible

Logo or 'break lines' Possible

Process tends itself to

Process Considerable

automation and easy training of

Operator training required Difficulty may arise

operator

Adaptability to GMP Multistage process

High Process stages Usually single stage Not usually possible apart

from enteric coating

Functional coatings Easily adaptable for controlled

release

Table B

[0079] Another type of coating is enteric coating, which is typically used to protect s tablet core from disintegration in an acidic environment of a patient's stomach for one or more of the following reasons: i) To prevent degradation of acid sensitive API; ii) To prevent irritation of stomach by certain drugs like sodium salicylate; iii) Delivery of API into intestine; and iv) To provide a delayed release component for repeat action tablet.

[0080] Several kinds of enteric layer systems are now available. In a one layer system, the coating formulation is applied in one homogeneous layer, which can be whites-opaque or colored. Benefit is only one application needed. In a two layer system, in order to prepare enteric tablets of high quality and pleasing appearance, the enteric formulation is applied first, followed by colored film. Both layers can be of enteric polymer, or only the basic layer may contain enteric polymer while top layer is a fast disintegrating and water-soluble polymer.

[0081] Ideal properties of enteric coating material include: i) resistance to gastric fluids; ii) susceptible/permeable to intestinal fluid; iii) compatibility with most coating solution components and the drug substrate; iv) formation of continuous film; v) nontoxic, inexpensive and easy to apply; and vi) ability to be readily printed.

[0082] Another possible type of coating is an enteric sugar coating. Here, the sealing coat is tailored to include one of the enteric polymers in sufficient quantity to pass the enteric test for disintegration. The sub coating and subsequent coating steps are then as for conventional sugar coating.

[0083] Another type of coating is an enteric film coating. Here, enteric polymers are capable of forming a direct film in a film coating process. Sufficient weight of enteric polymer has to be used to ensure an efficient enteric effect. Enteric coating can be combined with polysaccharides, which are enzyme degraded in colon e.g. cyclodextrin and galactomannan. [0084] Another type of coating is a controlled release coating, which may include polymers like modified acrylates, water insoluble cellulose (ethyl cellulose), etc.

[0085] Still another type of coating is a compressed coating. This type of coating requires a specialization tablet machine. Compression coating is not widely used, but it has advantages in some cases in which the tablet core cannot tolerate organic solvent or water and yet needs to be coated for taste masking or to provide delayed or enteric properties to the finished product and also to avoid incompatibility by separating incompatible ingredients.

[0086] Another type of coating is an electrostatic coating. Electrostatic coating is an efficient method of applying coating to conductive substrates. A strong electrostatic charge is applied to the substrate. The coating material containing conductive ionic species of opposite charge is sprayed onto the charged substrate. Complete and uniform coating of corners and adaptability of this method to such relatively nonconductive substrate as pharmaceutical is limited.

[0087] Still another type of coating is dip coating. Here, coating is applied to the tablet cores by dipping them into the coating liquid. The wet tablets are dried in a conventional manner in coating pan. Alternative dipping and drying steps may be repeated several times to obtain the desired coating. This process lacks the speed, versatility, and reliability of spray-coating techniques. Specialized equipment has been developed to dip-coat tablets, but no commercial pharmaceutical application has been obtained.

[0088] Still another type of coating is vacuum film coating. Vacuum film coating is a new coating procedure that employs a specially designed baffled pan. In operation, the pan is hot water jacketed, and it can be sealed to achieve a vacuum system. The tablets are placed in the sealed pan, and the air in the pan is displaced by nitrogen before the desired vacuum level is obtained. The coating solution is then applied with airless spray system. The evaporation is caused by the heated pan, and the vapor is removed by the vacuum system. Because there is no high-velocity heated air, the energy requirement is low and coating efficiency is high. Organic solvent can be effectively used with this coating system with minimum environmental or safety concerns.

[0089] One or more of the above types of coatings may be used to coat the tablet, or to coat a capsule, a caplet, or a gel cap as may be necessary. Decarboxylation

[0090] Raw cannabis mainly contains THCA which is not psychoactive. When cannabis is inhaled via smoking, the THCA molecule loses its carboxylic group (COOH) in the form of water vapor and carbon dioxide and becomes THC - which is psychoactive. This process of losing the carboxyl group is called "decarboxylation". THCA is one of a number of cannabinoid acids such as CBDA, CBGA etc. that undergoes this process when heat or drying is applied to cannabis.

[0091] When cannabis is smoked or vaporized, cannabis is decarboxylated by the heat.

However, without decarboxylation, cannabis that is ingested may not provide full effectiveness. Consequently, of it is intended to eat or digest cannabis to deliver a dosage of therapeutic active ingredients, then it is desirable to first decarboxylate the cannabis.

[0092] Basically, the goal of cannabis decarboxylation is to activate the cannabinoids with minimal vaporization of cannabinoids or terpenes (the ingredients responsible for how cannabis smells). The lower the temperature used for decarboxylation, the longer the decarboxylation time required, and reduced loss of terpenes due to vaporization. Heating the cannabis in a closed container will also help reduce the loss of cannabinoids and terpenes by trapping any vapor and allowing it to be reabsorbed into the cannabis material as it slowly cools down after being decarbed. Table C, below shows illustrative temperatures and an approximate range of times required to decarboxylate cannabis.

Table C

[0093] Significantly, over decarboxylation may cause the cannabis to have a more sedative effect, due to the degradation of THC into CBN. Furthermore, lower temperatures prevent terpenes from vaporizing, but allows the conversion rate of THC to CBN to become faster than the conversion of THCA to THC. At 70% decarboxylation, the amount of THC in the cannabis actually drops since it is converting faster into CBN than the THCA is converting into THC.

Blends

[0094] In another embodiment, the ingestible therapeutic plant source pill may include a blend of different plant source materials selected to alleviate specific conditions or ailments. These blends may be selected based on the active ingredients found in each plant source material, and the amount of each plant source material in the blend is proportional to the desired proportion of active ingredients.

[0095] As an illustrative example, THC (tetrahydrocannabinol) and CBD (cannabidiol) are the two most prominent chemical compounds in the cannabis plant. Consequently, the vast majority of research to date has focused on the ratio of these two cannabinoids.

[0096] THC is helpful for treating many, many ailments. Studies have shown that it has medicinal benefits for ALS (Lou Gehrig's disease), Alzheimer's, anxiety, arthritis, chemotherapy side effects, Crohn's Disease, chronic pain, fibromyalgia, HIV-related peripheral neuropathy, Huntington's Disease, incontinence, insomnia, multiple sclerosis, pruritus, sleep apnea, and Tourette Syndrome, among others. THC has even been shown to kill cancerous tumors, and to be therapeutic in the treatment of nausea and appetite loss. THC has also been found to alleviate spasticity in patients with multiple sclerosis. THC has also been found effective in treating difficult-to-treat nerve pain commonly found in amputees, AIDS patients, and patients with multiple sclerosis.

[0097] CBD is the other major medicinal compound identified so far, and interest in its effects is growing. It is non-psychoactive. CBD works through a number of complex mechanisms. Preclinical studies indicate that CBD has analgesic (pain-relieving), anticonvulsant, anti-psychotic and neuroprotective effects. Unlike THC, it does not bind to the CB1 or CB2 cannabinoids receptors, which is why it does not produce THC-like psychoactivity.

[0098] CBD is used to help with acne, ADD, anxiety, arthritis, chronic pain, depression, diabetes, Dravet syndrome, epilepsy, glaucoma, Huntington's Disease, multiple sclerosis, neuropathic pain, Parkinson's, and schizophrenia, just to name a few. CBD has also been shown to kill cancer cells.

[0099] Other important chemical compounds in the cannabis plant include THCA. Prior to drying, the chemical that becomes THC is known as THCA (tetrahydrocannibinolic acid). In its fresh form, THCA is non-psychoactive. Growing research is showing the benefits of juicing raw, fresh cannabis. It is believed that THCA has medicinal properties that are lost when the plant is dried, and it can be metabolized in much larger doses than THC, making it potentially more effective. THCA appears to help with chronic immune-system disorders, including potential treatment of chronic Lupus.

[00100] CBN (cannabinol) is another chemical compound found in the cannabis plant.

CBN is created when THC is exposed to light and oxygen. It's known to have some mild psychoactive effects, and it appears to increase the effects of THC. CBN may make users dizzy or groggy, and is not usually sought-after for medicinal purposes.

[00101] CBC (cannabichromene) is another chemical compound found in the cannabis plant. Evidence suggests that CBC it may play a role in the anti-inflammatory and anti-viral effects of cannabis, and may contribute to the overall analgesic effects of medical cannabis. A 201 1 study in the British Journal of Pharmacology found that CBD and CBC stimulated descending pathways of antinociception and caused analgesia by interacting with several target proteins involved in nociceptive control. It helps in fighting bacteria as an anti-fungal also as an anti-inflammatory, pain relief, anti-biotic, depression and brain growth.

Ratios of Compounds

[00102] Recent research has been done into CBD : THC ratios by the pharmaceutical industry, specifically around the GW Pharmaceuticals' Sativex, which has a 1 :1 ratio of THC and CBD. In the clinical trials phase of drug development, researchers examined the effects of THC, CBD, and combination extracts on sleep, pain control, and muscle spasms. They found that 1 : 1 CBD : THC extracts provided the most therapeutic relief across all categories.

[00103] CBD and THC combinations also show therapeutic promise across a number of disease states for which there has been limited therapeutic breakthrough to date. CBD modulates waking via activation of neurons in the hypothalamus and DRD (Dorsal Raphe Nucleus). Both regions are apparently involved in the generation of alertness. Also, CBD increases DA (Dopamine) levels as measured by microdialysis and HPLC procedures. Since CBD induces alertness, it might be of therapeutic value in sleep disorders such as excessive somnolence.

[00104] For example, in Amyotrophic Lateral Sclerosis (ALS), THC has been shown to delay motor deterioration and increase long term survival. Recent work has built on this study to show that the addition of CBD in conjunction with THC leads to a 14% increase in motor performance and an increase in survival beyond the survival rates with THC alone.

[00105] CBD and THC combinations have also been shown to increase alertness in some patients. By contrast, THC alone has more sedative effects. In fact, CBD is just an antagonist of CB1 receptors. It is probably true then that indica plants have a very high THC % compared to sativas and this has a stronger biphasic stimulant/sedative effect (CB1 receptors are the most widespread receptors in the brain, so its not unlikely that they can do both). The amount of CBD in most drug strains probably has no effect at all since CBD is not present in large amounts and has a much lower affinity for CB 1 receptors compared to THC.

[00106] Illustrative examples of CBD to THC ratios include the following:

[00107] 88: 1 - Non-psychoactive. Charlotte's Web is a well know example of a CBD dominant strain. Used to treat children with severe epilepsy and Dravet syndrome.

[00108] 18: 1 - Non-psychoactive. Some patients find CBD dominant medicines helpful for anxiety, depression, psychosis and other mood disorders.

[00109] 8:1 - Non-psychoactive. Some patients find mid-range CBD : THC" ratios helpful for spasms, convulsions, tremors, endocrine disorders, metabolic syndrome and overall wellness.

[00110] 4:1 Bordeline psychoactive. For patients who have some tolerance to THC.

Some patients find midrange ratios helpful for pain relief, immune support, and other health benefits.

[00111] 2:1 - Psychoactive in larger doses. For patients who have some tolerance for THC. Some patients find balanced ratios helpful for inflammation, chronic pain, gastrointestinal issues and stress relief.

[00112] 1 :1 - Psychoactive. For patients who tolerate THC well. Some patients find a balanced ratio helpful for neuropathic pain, rheumatism and overall mood enhancement. [00113] 1 : 4 - - Psychoactive. For patients who tolerate THC well. Higher levels of THC demonstrates analgesic, anti-emetic, and anti-inflammatory properties. Can also be used as a sleep aid due to its sedative effect. This ratio has been found to kill all forms of cancer in a Petri dish.

Dosing

[00114] A patient's sensitivity to THC (tetrahydrocannabinol) is a key factor to determining the appropriate ratio and dosage of high CBD cannabis medicine. CBD can lessen or neutralize the intoxicating effects of THC. So a greater ratio of CBD-to-THC means less of a "high." But CBD-dominant cannabis remedies with little THC, while not intoxicating, are not necessarily the most effective therapeutic option. That's because CBD and THC heighten one another's medicinal effects. A combination of CBD and THC will likely have a greater anticancer effect or analgesic (painkilling) effect, for example, than CBD or THC alone.

Packaging

[00115] Now referring to FIG. 2, in another embodiment, the ingestible therapeutic plant source pill may be individually sealed and packaged in blister packs. In another embodiment, the blister packs may be designed to be child resistant and/or senior friendly in order to increase safety and convenience. Furthermore, in addition to physically protecting the tablets, the blister packs can strictly control the amount of desired humidity in order to maintain freshness and increase longevity of the active ingredients. Alternatively, the ingestible therapeutic plant source pill may be packed loosely in a bottle.

[00116] In a preferred embodiment, each batch of plant source material is processed in preparation for packaging, such as by using MAP (Modified Atmosphere Packaging) techniques. MAP is the practice of modifying the composition of the internal atmosphere of a package (commonly food packages, drugs, etc.) in order to improve the shelf life.

[00117] The modification process often tries to lower the amount of oxygen (O2), moving it from 20.9% to 0%, in order to slow down the growth of aerobic organisms and the speed of oxidation reactions. The removed oxygen can be replaced with nitrogen (N ₂ ), commonly acknowledged as an inert gas, or carbon dioxide (CO2), which can lower the pH or inhibit the growth of bacteria. Carbon monoxide can be used for preserving the red color of meat. With starting material at 10% THC, (CBD, or combination of), 0.1 grams of material would provide the standard dose of 10 milligrams of active components (THC, CBD, or combination). Such a small amount could compress to an extremely small size, possibly too small to easily handle. An excipient would need to be added to make a pill of size 5; 1 1.1 mm long by 4.91 mm external diameter. Additional excipient could be added to make a pill of any size to size 00.

[00118] In another embodiment, each pill may include a label or a coating on at least one side of the pill, which label or coating may include identifying information.

[00119] Now referring to FIG. 3, shown is an illustrative process for preparing various forms of ingestible plant source pills. As shown, one or more pharmacologically active substances are proportioned together with or without an excipient, such that a consistent bulk may be obtained.

[00120] The proportion of pharmacologically active substances and possibly one or more excipients are then mixed in preparation for processing the mixture into one of granules, tablets, pills or capsules. The mixture may be processed through a granulation step to form granules, or further processed through compression or further granulation steps into tablets, or through a coating process into pills. In another embodiment, the granules may go through a filling process to be formed into capsules.

[00121] Thus, in an aspect, there is provided a process for forming an ingestible therapeutic plant source pill, comprising: testing potency of pharmacologically active substances in a plant source material; proportioning the pharmacologically active ingredients; mixing the pharmacologically active ingredients; and processing the mixture into one of granules, tablets, or capsules.

[00122] In an embodiment, the ingestible therapeutic plant source material is a cannabis plant.

[00123] In another embodiment, the process further comprises processing the ingestible therapeutic plant source material by one or more of drying, shredding, grinding, and mixing with one or more excipients. [00124] In another embodiment, the process further comprises proportioning the pharmacologically active ingredients comprises proportioning CBD (cannabidiol) and THC (tetrahydrocannabinol) in a desired ratio.

[00125] In another embodiment, the process further comprises compressing the ingestible therapeutic plant source material and the one or more excipients into a tablet.

[00126] In another embodiment, the process further comprises measuring ingestible therapeutic plant source material of known CBD and THC content to obtain a desired CBD : THC ratio; heating the ingestible therapeutic plant source material and the one or more excipients; compressing the heated ingestible therapeutic plant source material and the one or more excipients into a tablet; and cooling the compressed tablet.

[00127] In another embodiment, the process further comprises identifying the tablet by the CBD : THC ratio.

[00128] In another embodiment, the process further comprises identifying the tablet by dosage.

[00129] In another embodiment, the process further comprises reducing the bulk of non- therapeutic ingredients in the ingestible therapeutic plant source material prior to compressing the ingestible therapeutic plant source material into a tablet.

[00130] In another embodiment, the process further comprises: forming granules from the processed ingestible therapeutic plant source material; measuring granules of known CBD and THC content to obtain a desired CBD : THC ratio; and encapsulating the measured granules in a capsule.

[00131] In another embodiment, the process further comprises identifying the capsule by the CBD : THC ratio.

[00132] In another embodiment, the process further comprises identifying the capsule by dosage.

[00133] In another embodiment, the process further comprises straining the ingestible therapeutic plant source material in a solvent to form a viscous liquid; measuring viscous liquid of known CBD and THC content to obtain a desired CBD : THC ratio; evaporating the solvent to yield hash oil; and encapsulating the hash oil in a liquid gel capsule. [00134] In another embodiment, the solvent is one of isopropyl alcohol, ether, butane, propane, and C0 ₂ .

[00135] In another embodiment, the process further comprises identifying the liquid gel capsule by the CBD : THC ratio.

[00136] In another embodiment, the process further comprises identifying the liqud gel capsule by dosage.

[00137] In another aspect, there is provided an ingestible therapeutic plant source pill, comprising: pharmacologically active substances CBD (cannabidiol) and THC (tetrahydrocannabinol) in a known ratio; and identification of the CBD : THC ratio.

[00138] In an embodiment, the ingestible therapeutic plant source pill of claim 17, further comprising identification of the dosage.

[00139] In another embodiment, the ingestible therapeutic plant source pill is one of a compressed tablet, a capsule containing granules, or a liquid gel cap containing liquid.

[00140] While illustrative embodiments of the invention have been described above, it will be appreciate that various changes and modifications may be made without departing from the scope of the present invention. For example, while the tablet has been shown as a relatively flat, wide cylinder, it will be appreciated that this shape is not limiting. Alternatively, the tablet may be an elongated cylindrical shape which may obviate the need for through holes by increasing the surface area relative to the mass of the tablet.

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