Compressed pharmaceutical dosage form

Abstract

The present invention relates to compressed pharmaceutical dosage forms comprising paracetamol for oral administration and methods of manufacturing. Particularly, the pharmaceutical dosage form is a coated tablet that has a coating consisting of wax alone.

Description

[0001] COMPRESSED PHARMACEUTICAL DOSAGE FORM

[0002] Field of the Invention

[0003] The present invention relates to compressed pharmaceutical dosage forms comprising paracetamol for oral administration and methods of manufacturing. Particularly, the pharmaceutical dosage form is a coated tablet that has a coating consisting of wax alone.

[0004] Background of the Invention

[0005] Over-the-counter (OTC) oral tablets are widely used and are expected to be easy to swallow, pleasant in the mouth, and visually appealing. These attributes are commonly achieved by applying a coating during the final stage of manufacture.

[0006] Conventional coatings are typically polymer-based films produced by spraying aqueous polymer dispersions onto the tablets in a rotating pan followed by warm-air drying. Sugar coatings may also be used. Such coatings can mask taste, provide colour, and offer varying degrees of protection from moisture, oxygen or light. A wax polishing step is sometimes added for the purposes of imparting a glossy finish that is more attractive to consumers.

[0007] Despite their widespread adoption, polymeric film coatings have recognised limitations. Film-forming polymers often create hydrophilic, higher-friction surfaces that may exhibit drag or adhesion during swallowing. Coating systems that include titanium dioxide opacifiers can show susceptibility to light-induced discolouration, leading to aesthetic changes over shelf-life. In addition, polymer films can influence surface chemistry at the tablet interface, which may be relevant for active ingredients such as paracetamol that are known to generate surface degradants under certain conditions.

[0008] From a manufacturing perspective, film coating is time-intensive, requiring extended spray and drying stages, elevated energy consumption, and long residence times in rotating drums. These factors increase cost and can contribute to tablet attrition, breakage, static build-up and dust generation, which in turn can cause disruption in downstream bottling or blistering operations.There is therefore a need for alternative coating strategies that deliver acceptable swallowability, appearance and handling characteristics without relying on polymeric or titanium dioxide-based film systems and without the production inefficiencies inherent to conventional coating processes.

[0009] Summary of the Invention

[0010] The present Invention addresses manufacturing and downstream handling challenges by employing a non-polymeric, wax-only monolayer coating whilst maintaining swallowability and appearance. The coating may serve to reduce dust generation and static-related fouling during conveying, bottling and blistering. In addition, the wax-only coating enables shorter coating cycle times and reduced energy consumption relative to polymer-film and sugar-coating processes.

[0011] Thus, in a first aspect of the Invention, there is provided a compressed pharmaceutical dosage form for oral administration comprising paracetamol (APAP) and one or more pharmaceutically acceptable diluents, excipients or carriers, wherein the pharmaceutical dosage form is a coated tablet, wherein the coating consists of wax and wherein the total weight of wax is from about 0.01% w / w to about 0.5% w / w based on the weight of the tablet core.

[0012] In some embodiments, the total weight of wax is from 0.02% w / w to 0.5% w / w, such as 0.03%w / w to 0.3% w / w or 0.05% w / w to 0.3% w / w.

[0013] The wax is present as a continuous phase forming a coherent monolayer, not as discrete particles or discontinuous patches. Particularly the wax coating covers at least 95%, more preferably at least 99% and yet more preferably 100% of the tablet core external surface, as determined by optical microscopy or micro-CT segmentation. Particularly, the wax coating has a mean thickness of at least 2-5 pm, for example, measured by cross-sectional microscopy.

[0014] Particularly, the compressed pharmaceutical dosage form may further comprise ibuprofen, dexibuprofen, diphenhydramine chloride or caffeine.

[0015] Particularly, the compressed pharmaceutical dosage form may comprise from 200mg to lOOOmg of paracetamol and from 80mg to 400mg of ibuprofen orequivalent ibuprofen salt. In certain embodiments, the compressed pharmaceutical dosage form may comprise 250mg of paracetamol and 125mg of ibuprofen or equivalent ibuprofen salt. In other embodiments, the compressed pharmaceutical dosage form may comprise 500mg of paracetamol and 250mg of ibuprofen or equivalent ibuprofen salt.

[0016] Particularly, the compressed pharmaceutical dosage form may comprise from 200mg to lOOOmg of paracetamol and from 40mg to 400mg of dexibuprofen or equivalent dexibuprofen salt, for example, 50mg, 60mg, 62.5mg, 65mg, lOOmg, 125mg, 200mg, 300mg or 400mg of dexibuprofen. In certain embodiments, the compressed pharmaceutical dosage form may comprise 250mg of paracetamol and about 62.5mg of dexibuprofen. In other embodiments, the compressed pharmaceutical dosage form may comprise 500mg of paracetamol and about 125mg of dexibuprofen.

[0017] The compressed pharmaceutical dosage form may comprise from 200mg to lOOOmg of paracetamol and from 50mg to 65mg of caffeine, particularly 65mg of caffeine.

[0018] The compressed pharmaceutical dosage form may comprise 500mg of paracetamol and 25mg of diphenhydramine chloride.

[0019] Particularly, the wax is selected from the group consisting of carnauba wax, candelilla wax, beeswax (white or yellow), hard paraffin wax, cetyl palmitate, rice bran wax, and combinations thereof. Preferably, the wax is carnauba wax. The wax may optionally be coloured with a colouring agent.

[0020] Preferably, compressed pharmaceutical dosage forms of the invention are free of polymeric film-forming materials and titanium dioxide.

[0021] In a Second Aspect of the Invention, there is provided a method of manufacturing the compressed pharmaceutical dosage form of the First Aspect.

[0022] Particularly, the method for manufacturing the compressed pharmaceutical dosage form comprises the steps of preparing a tablet core and directly coating the outer surface of the tablet core with a coating consisting of wax. Particularly, the totalweight of wax is from about 0.01% w / w to about 0.5% w / w based on the weight of the tablet core. Preferably, the wax is carnauba wax.

[0023] Particularly, the step of directly coating the outer surface of the tablet core with a coating consisting of wax may comprise, transferring a tablet core into a coating pan, adding a wax powder to the coating pan, heating and rotating the coating pan.

[0024] Particularly, the step of directly coating the outer surface of the tablet core with a coating consisting of wax may comprise spraying molten wax onto the tablets.

[0025] The method for manufacturing may further comprise the step of packaging the coated tablets.

[0026] In high-throughput manufacturing, friable edges and uncoated surface micro-asperities may contribute to fines generation ("dust"), which increases airborne particulates, sensor fouling, and line stoppages.

[0027] Particularly, coated tablets of the invention exhibit reduced dust generation during simulated handling whilst maintaining swallowability relative to polymer-coated references. Dust reduction may be quantified by a Dust Emission Index (DEI) test. For example, a lot of 100 tablets is tumbled in a stainless-steel drum (diameter ~200mm) at 10 rpm for 10 min with four 10 mm PTFE baffles. The exhaust passes through a pre-weighed 1 pm glass-fiber filter. The Dust Emission Index (mg / 100 tablets) is the mass gain of the filter. Particularly, coated tablets exhibit DEI < 5 mg / 100 tablets, more particularly < 3 mg / 100 tablets under these conditions.

[0028] Airborne particulate reduction during packaging may be quantified by an Airborne Particle Burden test. For example, tablets are conveyed at 100-200 cpm under a sampling probe connected to an optical particle counter. Particle counts >0.5 pm and >5.0 pm are recorded over 5 min at a fixed probe geometry. APB scores are reported as particles / ft3(or particles / L). Particularly, coated compressed pharmaceutical dosage forms of the invention exhibit an Airborne Particle Burden score (>0.5 pm) at least 10% lower than polymer film-coated reference tablets produced from the same core composition.Brief description of Figures

[0029] Figure 1: Experimental set-up for a comparative slide test to compare a commercial product with a product according to the invention; (1) stainless-steel ramp, (2) ramp angle, (3) slide lane, (4) paper ribbon, slide borders, (5) test tablet.

[0030] Figure 2: Results of a comparative slide test comparing a commercial product with a product according to the invention.

[0031] Description of the Invention

[0032] The present invention provides coated compressed pharmaceutical dosage forms, such as tablets, that offer acceptable patient experience and appearance whilst avoiding the disadvantages of polymer- and sugar-based coating systems, particularly with respect to swallowability, light stability and manufacturing efficiency. The invention further provides more sustainable and efficient methods for producing coated tablets by reducing the cost, energy use and operational complexity inherent in conventional coating processes. It has been found that a coating consisting solely of wax provides an unexpectedly simple and resource-efficient manufacturing approach while maintaining the key attributes normally delivered by coated pharmaceutical dosage forms, including acceptable appearance and patient experience.

[0033] There is therefore provided a compressed pharmaceutical dosage form, such as a coated tablet for oral administration, comprising a compressed core and a coating consisting of wax, the wax being present in a total amount of about 0.02% w / w to about 0.5% w / w based on the weight of the tablet core. The compressed pharmaceutical dosage form is formed from the compressed core and the directly applied wax coating, which together define the full coated structure. Compressed pharmaceutical compositions of the invention consist of a compressed core (e.g. a tablet core) and a coating consisting of wax.

[0034] Pharmaceutical dosage forms are dosage forms comprising a safe and effective amount of at least one active ingredient and pharmaceutically acceptable excipients in final form suitable for administration to a patient. The dosage forms are for oraladministration, via the mouth, intended to be delivered to or released in the stomach or small intestine of a patient.

[0035] The terms "compressed core" and "tablet core" refer to a non-liquid oral dosage form intended to be swallowed and having a sufficiently defined form to be coated. Preferably the composition of the tablet core is a homogenous composition in which paracetamol and one or more pharmaceutically acceptable diluents, excipients or carriers are blended together to form a homogenous solid core with a uniform structure or composition throughout, free of discreet zones or layers of the active agent combinations. The homogenous solid core is formed by compression methods known in the art using conventional equipment and processes, for example by compressing uniform volumes of powder, particles or particle aggregates produced by granulation methods.

[0036] The tablet core may be of any size or shape known in the art, such as, by way of non-limiting example round, elliptical, oval, square or triangular.

[0037] The compressed pharmaceutical dosage form, may comprise one or more debossed patterns, applied to the tablet core, such as, by way of non-limiting example, at least one letter and / or at least one number. Surprisingly, the use of a wax coating consisting of about 0.02% w / w to about 0.5% w / w of wax based on the weight of the tablet core, does not fill the debossed pattern, retaining the 'crispness' of the edges of the pattern and enabling, for example, tablet identification without the need for ink.

[0038] The tablet core is directly coated with a coating consisting of wax, the total weight of the wax being from about 0.01% w / w to about 0.5% w / w based on the weight of the tablet core. For example, from 0.01% w / w to 0.5% w / w, from 0.01% w / w to 0.45% w / w, from 0.01% w / w to 0.40% w / w, from 0.01% w / w to 0.35% w / w, from 0.01% w / w to 0.30% w / w, from 0.01% w / w to 0.25% w / w, from 0.01% w / w to 0.20% w / w, from 0.01% w / w to 0.15% w / w or from 0.01% w / w to 0.10% w / w. For example, from 0.02% w / w to 0.5% w / w, from 0.02% w / w to 0.45% w / w, from 0.02% w / w to 0.40% w / w, from 0.02% w / w to 0.35% w / w, from 0.02% w / w to 0.30% w / w, from 0.02% w / w to 0.25% w / w, from 0.02% w / w to 0.20% w / w, from 0.02% w / w to 0.15% w / w or from 0.02% w / w to 0.10% w / w. For example, about0.01% w / w, 0.02% w / w, 0.03% w / w, 0.04% w / w, 0.05% w / w, 0.06% w / w, 0.07% w / w, 0.08% w / w, 0.09% w / w, 0.10% w / w, 0.15% w / w, 0.20% w / w, 0.25% w / w, 0.30% w / w, 0.35% w / w, 0.40% w / w, 0.45% w / w or 0.50% w / w. In some embodiments, approximately 0.079kg of wax is used per 400kg of tablet cores.

[0039] The term "coating" refers to a substantially continuous, preferably continuous, layer surrounding the core of the compressed pharmaceutical composition. The term "directly coated" refers to a configuration whereby the layer of wax is applied to the surface of the compressed core with no intervening layers or structures present between the compressed core and the coating layer. The layer of wax is the only coating applied. Thus, the wax coating directly contacts the surface of the compressed core and forms the outer surface of the dosage form that is exposed to the atmosphere or external environment, i.e. it is a single, monolayer coating of wax with no additional material added between the compressed core and the wax layer or beyond the wax layer. For the avoidance of doubt, the compressed pharmaceutical dosage form does not comprise any polymeric film layer or sugar-coating layer beneath the wax, and the wax layer is the outermost and only coating. Particularly, the dosage form is constructed only of the compressed core and the wax coating, which together constitute the complete coated unit. More particularly, the compressed pharmaceutical dosage form consists of a compressed core directly enveloped by a wax coating as the exclusive, only, coating layer.

[0040] The coating covers at least 95%, at least 98%, at least 99%, 100% of the external tablet surface as measured by optical microscopy; and / or (ii) the wax coating has a mean thickness of at least 2 pm, at least 3 pm, at least 4 pm or at least 5 pm measured on a tablet cross-section; and / or (iii) the wax is applied in molten form to produce a fused monolayer.

[0041] The compressed pharmaceutical dosage forms comprise paracetamol. In certain embodiments, the compressed pharmaceutical dosage forms comprise paracetamol and at least one other active pharmaceutical ingredient (API). An "active pharmaceutical ingredient" is a term used in the art to refer to a drug substance or mixture of drug substances intended to be used in the manufacture of a drug product and that, when used in the production of a drug, becomes an activeingredient in the drug product. Such substances have pharmacological activity within the body of a patient.

[0042] Particularly, the at least one other API is useful for treating a variety of types of pain. The term "pain" encompasses both acute and chronic pain. Acute pain means immediate, generally high threshold, pain brought about by physical injury such as a cut, crush or burn for example. Chronic pain is pain other than acute pain and includes, without limitation, neuropathic pain, visceral pain, inflammatory pain, headache pain, muscle pain and referred pain. Chronic pain may be of relatively long duration, for example, months or years and can be continuous or it may be intermittent, such as headache pain. Particular types of pain include headache pain, menstrual pain, dental pain, jaw pain and arthritis pain.

[0043] Particularly, the at least one other API is selected from the group consisting of naproxen, ibuprofen, dexibuprofen, diphenhydramine chloride and caffeine.

[0044] It should be understood that reference to naproxen, ibuprofen and dexibuprofen herein is also intended to include their pharmaceutically acceptable salts, for example, ibuprofen lysine, naproxen sodium and the like.

[0045] Preferably the at least one other API is selected from the group consisting of ibuprofen and dexibuprofen.

[0046] Particularly, the compressed pharmaceutical dosage form may comprise from 200mg to lOOOmg of paracetamol and from 80mg to 400mg of ibuprofen or equivalent ibuprofen salt. In certain embodiments, the compressed pharmaceutical dosage form may comprise from 80mg to 400mg of ibuprofen or equivalent ibuprofen salt. In certain embodiments, the compressed pharmaceutical dosage form may comprise from 200mg to lOOOmg of paracetamol and from 80mg to 400mg of ibuprofen or equivalent ibuprofen salt.

[0047] Particularly, the compressed pharmaceutical dosage form may comprise from 40mg to 200mg of dexibuprofen or equivalent dexibuprofen salt. In certain embodiments, the compressed pharmaceutical dosage form may comprise from 200mg to lOOOmgof paracetamol and from 40mg to 200mg of dexibuprofen or equivalent dexibuprofen salt.

[0048] The compressed pharmaceutical dosage form may comprise from 200mg to lOOOmg of paracetamol and from 125mg to 500mg of naproxen or equivalent naproxen salt.

[0049] In certain embodiments, the pharmaceutical dosage form may comprise from 200mg to lOOOmg of paracetamol and at least one other API selected from the group consisting of caffeine, diphenhydramine chloride, phenylephrine HCI and pseudoephedrine.

[0050] The compressed pharmaceutical dosage form may comprise 500mg of paracetamol and 25mg of diphenhydramine chloride.

[0051] Compressed pharmaceutical dosage forms of the Invention comprise one or more pharmaceutically acceptable diluents, excipients or carriers including, but not limited to, polymers, resins, plasticizers, fillers, lubricants, binders, disintegrants, solvents, cosolvents, surfactants, preservatives, sweetener agents, flavouring agents, buffer systems, pharmaceutical-grade dyes and pigments.

[0052] Preferably, the wax is selected from the group consisting of carnauba wax, candelilla wax, beeswax (white or yellow), hard paraffin wax, cetyl palmitate, rice bran wax, and combinations thereof. More preferably, the wax is carnauba wax. In some embodiments, the wax may be a coloured wax, for example, coloured with a colouring agent.

[0053] There is also provided a method of manufacturing the compressed pharmaceutical dosage form. Particularly, the method for manufacturing the compressed pharmaceutical dosage form comprises the steps of preparing an uncoated tablet core and directly coating the outer surface of the tablet core with a coating consisting of wax.

[0054] Particularly, the method for manufacturing the compressed pharmaceutical dosage form comprises the steps of preparing an uncoated tablet core and directly coating the outer surface of the tablet core with a coating consisting of wax.Particularly, the method for manufacturing the compressed pharmaceutical dosage form comprises the steps of preparing an uncoated tablet core and a coating step consisting of directly coating the outer surface of the tablet core with a coating consisting of wax.

[0055] Particularly, the total weight of wax is from about 0.01% w / w to about 0.5% w / w based on the weight of the tablet core. Preferably, the wax is carnauba wax. Particularly, about 0.079kg of wax is used per 400kg of tablet cores.

[0056] Coating can be achieved by methods known to one skilled in the art such as by using fluidized bed equipment, rotating pharmaceutical pan, compression coating, spray coating or drenching. For example, wax may be applied onto the uncoated tablet core by spraying using any suitable spray equipment known in the art. In certain embodiments, the tablet core is coated by continuous spray methods.

[0057] Particularly, the step of directly coating the outer surface of the uncoated tablet core with a coating consisting of wax may comprise, transferring an uncoated tablet core into a coating pan, adding a wax powder to the coating pan, heating and rotating the coating pan.

[0058] Particularly, the step of directly coating the outer surface of the uncoated tablet core with a coating consisting of wax may comprise spraying molten wax onto the uncoated tablet core. Particularly, the step of directly coating the outer surface of the uncoated tablet core with a coating consisting of wax may comprise spraying molten wax onto the uncoated tablet core.

[0059] Particularly, the step of directly coating the outer surface of the uncoated tablet core comprises applying a wax coating having a total weight of from about 0.01% w / w to about 0.5% w / w based on the weight of the tablet core.

[0060] In preferred embodiments, the step of directly coating the outer surface of the uncoated tablet core with a coating consisting of wax may comprise, transferring an uncoated tablet core into a coating pan, adding a wax powder to the coating pan,heating and rotating the coating pan until the wax coating has a total weight of from about 0.01% w / w to about 0.5% w / w based on the weight of the tablet core.

[0061] Particularly, the coating step maintains tablet-surface temperatures at > 35-40°C to enable wax softening and adhesion.

[0062] In certain embodiments, coating is achieved under pan rotation of 2-6 rpm for at least 3 minutes after wax addition, with concurrent application of heated inlet air (25-50°C). In certain embodiments, the wax is applied as a molten spray to form a continuous, fused monolayer. Particularly, the variation in wax mass across 20 randomly sampled tablets is <10%, more particularly <5%, yet more particularly <1%.

[0063] The method for manufacturing may further comprise the step of packaging the coated tablets.

[0064] General

[0065] The term "comprising" encompasses "including" e.g. a composition "comprising" X may include something additional e.g. X + Y. In some implementations, the term "comprising" refers to the inclusion of the indicated active agent, such as recited compounds, as well as inclusion of other active agents, and carriers, excipients, emollients, stabilizers, etc., known in the consumer health industry and generally recognized as safe (GRAS). Use of the transitional phrase "consisting essentially of" means that the scope of a claim is to be interpreted to encompass the specified materials or steps recited in the claim, and those that do not materially affect the basic and novel characteristic(s) of the claimed invention. See, In re Herz, 537 F.2d 549, 551-52, 190 USPQ 461, 463 (CCPA 1976) (emphasis in the original); see also MPEP § 2111.03. Thus, the term "consisting essentially of" when used in a claim of this invention is not intended to be interpreted to be equivalent to "comprising". The term "consisting of" and variations thereof means including and limited to (for example, the specific recited constituent(s) or steps). In certain territories, the term "comprising an active ingredient consisting of" may be used in place of "consisting essentially". The term "about" in relation to a numerical value x is optional and means, for example, that the numerical value may comprise some variance around the stated number to allow for routineexperimental fluctuation, measurement variance or to encompass minor deviations that may achieve substantially the same results as the stated number, such as x±10%, x±5%, x±4%, x±3%, x±2% or x±l%. The word "substantially" does not exclude "completely" e.g. a composition which is "substantially free" from Y may be completely free from Y. Where necessary, the word "substantially" may be omitted from the definition of the invention. All percentages and ratios used herein are by weight of total composition, unless otherwise indicated. For the avoidance of doubt, reference to percent by weight, "X% by weight", "X% w / w" and the like means by weight of the total composition, the amount of each ingredient being selected so that total ingredients in the composition sum to 100 percent by weight.

[0066] All references or patent applications cited within this patent specification are incorporated by reference herein. In order that this invention may be better understood, the following examples are set forth. These examples are for purposes of illustration only and are not to be construed as limiting the scope of the invention in any manner.

[0067] Examples:

[0068] Example 1:

[0069] A pharmaceutical composition comprising 500mg of Paracetamol and 25mg of diphenhydramine chloride as active pharmaceutical ingredients (APIs) was prepared.

[0070]

[0071]

[0072] Diphenhydramine is an antihistamine used to relieve symptoms of allergy, hay fever, and the common cold. In combination with paracetamol, it is often also used to induce or improve sleep. Such combination products are currently marketed under the brand name Panadol® as "Panadol Night". However, these products have a film coating comprising a polymer, plasticizer and a pigment, which comes with the disadvantages described above.

[0073] Manufacturing Method:

[0074] Uncoated tablets were manufactured according to conventional processes well known to the person skilled in the art. The uncoated tablets were placed in a Vector Hi-Coater 170 coating pan. The air temperature was set to 40°C (Range 25 to 50°C), and the air heater is started. The tablets are allowed to warm with jogging intermittently, until the outlet temperature reaches 35°C. When the outlet temperature reached 35°C, the pan was rotated slowly (RPM < 2) until the temperature stabilised at > 35°C.

[0075] Parameter ranges were set as follows:

[0076]

[0077] *lnlet air volume and temperature may be adjusted in order to achieve the desired exhaust temperature ranges.

[0078] **Pan speed RPM may be adjusted to achieve a good tablet mixing action inside the pan.The inlet I exhaust air was turned off, and carnauba wax was added to the rolling tablet bed and the pan rotated for 3 minutes. Approximately 0.079kg of carnauba wax is used per 400kg of tablets. The inlet I exhaust air was turned on, following which the pan was rotated for a further 5 minutes. Inlet air was then turned off and the pan rotated for further 5 minutes. The tablets are continuously jogged until the exhaust air temperature has dropped to <40°C. The average weight of the wax coated tablets was then determined, and the tablets filled into double lined fibre board drums before being packed into blisters, containers, or other suitable packaging.

[0079] Film coating of a comparable commercial product (such as Panadol Night) takes approximately 3.5 hours to complete whilst the process described above was completed in approximately 20 minutes.

[0080] Example 2:

[0081] A pharmaceutical composition comprising 500mg of Paracetamol, 25mg of caffeine, and 5mg of phenylephrine HCI was prepared:

[0082]

[0083] Caffeine stimulates the central nervous system making cold & flu patients suffering from fatigue more alert. Phenylephrine HCI is used for the temporary relief of stuffynose, sinus, and ear symptoms caused by the common cold, flu, allergies, or other breathing illnesses. Such combination products are currently marketed under the brand name Panadol ® as "Panadol Cold & Flu" or under the brand Beechams ® as "Beechams Flu Plus". However, the current Panadol Cold & Flu products have a film coating comprising a polymer, plasticizer and a pigment, which comes with the disadvantages described above. The manufacturing process was the same as for Example 1 and coating was completed in approximately 20 minutes.

[0084] Example 3:

[0085] A pharmaceutical composition comprising 250mg of Paracetamol and 125mg of Ibuprofen was prepared:

[0086]

[0087] Such combination products are currently marketed under the brand name Advil ® as "Advil Dual Action". The manufacturing process was the same as for Example 1 and coating was completed in approximately 20 minutes.

[0088] Example 4 - Comparative Slide Test

[0089] An in-vitro study was conducted to understand the effect of a wax-only coating on the swallowability and flowability of the tablets. The studies involved the determination of the angle of slide.

[0090] The angle of slide is the angle at which the caplets overcome inertia and I or friction and move / slide down an inclined plane without tumbling. The lower the angle of slide, the greater is the lubricity or slipperiness of the tablets. This further is corelated to the ease of swallowability and performance on packaging operation.

[0091] The study compared the commercially available Panadol Night tablets with the formulation according to Example 1. The commercially available Panadol Night product is based on the same uncoated tablet as the formulation of Example 1, but it is coated with an Opadry II Blue 33G20500 film coating, with each tablet comprising 19mg of coating, resulting in a total tablet weight of 638mg.

[0092] The experimental set-up is shown in Fig. 1.

[0093] 1. A stainless-steel ramp was used to slide the tablets. A slide lane was established in the middle of the ramp using a paper ribbon.

[0094] 2. 20 tablets from each sample were left at the top of ramp and observed for complete slide through the ramp.

[0095] 3. The ramp angle was adjusted to an angle in which none of the 20 tablets from both samples slide through the ramp.

[0096] 4. Ramp angle was gradually increased after each run, noting down the number of tablets from each sample that slid through the entire ramp. The way in which tablets slide (flat or rotating) was also noted.

[0097] The results are shown in Figure 2.Both formulations show the same angle of slide ranges, with no sliding at 5°, slide start at 10° and complete slide of all samples tested at 30°. The number of tablets sliding the entire ramp increases gradually with the increase of the ramp angle on both products. The tablets coated with wax showed only a slight decrease in the flowability with respect to the commercial product, more relevant at low angles. Tablets coated with wax only show almost the same trend to tumble when sliding through the ramp as the commercial product (data not shown).

[0098] The differences observed on the capacity to slide the ramp and the trend to rotate between both products, original and wax only, were not considered significant. Based on these tests, replacement of a film coating with a coating consisting of wax only would not affect a patient's perception of swallowability. However, in terms of processing, the use of a coating consisting of wax alone simplified processing whilst significantly reducing time needed to complete the process. Importantly, the new process represented a significant saving in terms of energy.

[0099] Whilst specific embodiments have been described, these are provided by way of example only. It will be understood by those skilled in the art that various changes in form and detail may be made without departing from the spirit and scope of the invention as set forth in the appended claims.

Claims

CLAIMS1. A compressed pharmaceutical dosage form for oral administration comprising paracetamol (acetaminophen) and one or more pharmaceutically acceptable diluents, excipients or carriers, wherein the pharmaceutical dosage form is a coated tablet, wherein the coating consists of wax and wherein the total weight of wax is from about 0.01% w / w to about 0.5% w / w based on the weight of the tablet core.

2. The compressed pharmaceutical dosage form of claim 1, further comprising ibuprofen or dexibuprofen.

3. The compressed pharmaceutical dosage form of claim 2 comprising from 200mg to lOOOmg of paracetamol and from 80mg to 400mg of ibuprofen or equivalent ibuprofen salt.

4. The compressed pharmaceutical dosage form of claim 2 comprising from 200mg to lOOOmg of paracetamol and from 40mg to 200mg of dexibuprofen or equivalent dexibuprofen salt.

6. The compressed pharmaceutical dosage form of claim 2 comprising from 200mg to 500mg of paracetamol and 50mg to 65mg of caffeine.

7. The compressed pharmaceutical dosage form of any preceding claim wherein the wax is selected from the group consisting of carnauba wax, candelilla wax, beeswax (white or yellow), hard paraffin wax, cetyl palmitate, rice bran wax, and combinations thereof.

8. The compressed pharmaceutical dosage form of claim 7, wherein the wax is carnauba wax.

9. The tablet of any preceding claim, wherein (i) the coating covers at least 95% of the external tablet surface as measured by optical microscopy; and / or (ii) the wax coating has a mean thickness of at least 2 pm, measured on a tabletcross-section; and / or (iii) wherein the wax is applied in molten form to produce a fused monolayer.

10. A method for manufacturing the compressed pharmaceutical dosage form of claims 1 to 9, the method comprising the steps of preparing an uncoated tablet core and directly coating the outer surface of the uncoated tablet core with a coating consisting of wax.

11. The method for manufacturing of claim 10, wherein the step of directly coating the outer surface of the uncoated tablet core with a coating consisting of wax comprises, transferring an uncoated tablet core into a coating pan, adding a wax powder to the coating pan, heating and rotating the coating pan.

12. The method for manufacturing of claim 10 or 11, wherein the step of directly coating the outer surface of the uncoated tablet core with a coating consisting of wax comprises spraying molten wax onto the tablet cores to provide coated tablets.

13. The method for manufacturing of claim 10, 11 or 12, further comprising the step of packaging the coated tablets.

14. The method for manufacturing of any one of claims 10 to 13, wherein the wax is carnauba wax.

15. The method of any one of claims 10 to 14, wherein the tablet temperature is maintained at >35°C during coating to soften the wax and promote formation of a continuous layer.

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