HK1209372A1 - Low melting propionic acid derivative particles for use in oral dosage forms - Google Patents
Low melting propionic acid derivative particles for use in oral dosage forms Download PDFInfo
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- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
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- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/145—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic compounds
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- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/148—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with compounds of unknown constitution, e.g. material from plants or animals
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- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
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- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
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- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
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Abstract
Low melting propionic acid derivative particles that are free flowing and have significantly reduced or eliminated throat burn are disclosed. A method of manufacturing the low melting propionic acid derivative particles; dosage forms containing the low melting propionic acid derivative particles; methods of manufacturing the dosage forms; and methods of treatment using the dosage forms are also disclosed.
Description
Technical Field
The present invention relates to low melting propionic acid derivative particles that are free flowing and have a significantly reduced or eliminated throat burn or burning sensation in the mouth and throat. The invention also relates to a method for producing taste-masked low-melting propionic acid derivative particles; a method for producing controlled-release low-melting propionic acid derivative particles; dosage forms comprising these low melting propionic acid derivative particles; methods of making these dosage forms; and methods of treatment using these dosage forms.
Background
The present invention relates to low melting propionic acid derivative particles, and more particularly to low melting propionic acid derivative compositions comprising low melting propionic acid derivative particles with reduced or no throat burn characteristics. The invention is particularly useful for manufacturing dosage forms containing low melting propionic acid derivative compounds such as ibuprofen, ketoprofen, dexibuprofen, and the like.
Child medication is often a challenging task for caregivers, primarily because of the bitter taste associated with many drugs. Chewable tablets or powders are one of many formulations that can address these challenges. A variety of flavors and sweeteners have been added to pharmaceuticals in order to make them more palatable and to mask the unpleasant taste and aftertaste that is common in many pharmaceuticals. Certain pharmaceutical ingredients, when administered in the form of chewable tablets, swallowable powders/granules, suspensions and uncoated tablets, in addition to having an unpleasant taste, also produce a burning or grating sensation in the mouth and/or throat. Flavors and sweeteners are less effective in overcoming this throat burning sensation. Despite the considerable effort expended in finding effective ways to eliminate this burning, there remains a need for methods to effectively eliminate the burning sensation of a medicament, preferably so that burning can be reduced to a level that allows for the provision of chewable compositions.
Propionic acid derivatives are used to relieve pain, tenderness, swelling and stiffness caused by osteoarthritis (arthritis due to the destruction of the joint lining) and rheumatoid arthritis (arthritis due to the swelling of the joint lining). They are also used to relieve mild to moderate pain, including menstrual pain (pain occurring before or during the menstrual period). Propionic acid derivatives are also useful for reducing fever and relieving mild pain of headache, myalgia, arthritis, menstrual period, common cold, toothache and backache. For example, ibuprofen (a propionic acid derivative of the class of drugs known as NSAIDs) acts by preventing the body from producing substances that cause pain, fever and inflammation.
Propionic acid derivatives have unpleasant burning sensation in the mouth and throat after ingestion. Several methods have been proposed in the art to overcome this burning sensation.
Japanese patent application 91997-. This patent application discloses the separation of ibuprofen from its racemic mixture to form an oral pharmaceutical composition containing only S (+) -ibuprofen and essentially no R (-) -ibuprofen. Although this approach may provide a more palatable form of ibuprofen, separation and isolation of the enantiomers is difficult.
U.S. patent No. 5,320,855 to McNeil-PPC, inc, discloses a method of masking the taste of ibuprofen by: granulating with polyvinylpyrrolidone, sodium carboxymethyl starch and sodium lauryl sulfate, and coating the obtained granule with hydroxyethyl cellulose or mixture of hydroxyethyl cellulose and hydroxypropyl methyl cellulose. Although resulting in an improvement in taste, this approach does not completely eliminate the "throat burn" associated with ibuprofen in chewable dosage forms.
U.S. patents 6,627,214 and 7,078,053 to McNeil-PPC, inc. disclose methods of inhibiting the burning sensation of a racemic mixture of propionic acid derivatives by: fumaric acid is generally provided in an amount of about 50% to about 150% by weight relative to the propionic acid derivative dose. While fumaric acid is effective in reducing burning sensation, proportionally higher levels of fumaric acid may cause a degree of sourness, which may make convenient dosage forms such as fast dissolving tablets and chewable tablets less palatable. Another approach is to coat the ibuprofen particles with hydrocolloids and fumaric acid in order to minimize irritation of the throat mucosa, as disclosed in us patent 4,762,702 to Gergely et al. Since hydrocolloids are hydrophilic, they allow water to be rapidly absorbed into the drug particles after ingestion, thereby disadvantageously reducing the burn-masking effect of the coating. Yet another approach is to mix an acid compound (such as fumaric acid) with an active ingredient coated with a taste-masking film comprising a polymer that is insoluble in an acidic environment and soluble at a pH of 5 or higher, as disclosed in U.S. patent No. 5,409,711 to Eurand International, SpA.
U.S. patent application 20080113021 to Shen discloses a dosage form capable of being chewed or disintegrated in the mouth prior to swallowing, the dosage form comprising: a plurality of particles comprising a propionic acid derivative (such as ibuprofen) and a taste-masking effective amount of a water-soluble acid having a solubility greater than about 10g/100mL water at 20 ℃; and a matrix comprising an acid having a solubility at 20 ℃ of less than about 5g/100mL of water.
U.S. patent 6,117,452 to Fuisz Technologies Ltd discloses microspheres containing a combination of glyceryl monostearate and polyethylene glycol glyceryl palmitostearate. This reference discloses that microspheres can be easily treated, for example with taste masking and/or controlled release coatings.
U.S. patent No. 5,405,617 to McNeil-PPC, inc, discloses a method of preparing a pharmaceutical matrix without the use of organic and/or volatile solvents, the method comprising melting a taste-masking amount of an aliphatic ester or fatty acid ester; admixing at least one pharmaceutically active substance with a molten aliphatic ester or fatty acid ester; and allowing the blend to cure.
European patent EP818992B1 to Eurand America, inc. discloses a taste masked, water insoluble NSAID comprising separate microcapsules simultaneously microencapsulated with gelatin and cellulose acetate phthalate.
European patent EP1301176B1 to Gattefosse Holding discloses a process for coating solid particles with a hot melt.
European patent application EP2198856a1 to Reckitt benckkiser Healthcare discloses a process for preparing a granular composition of solidified melt granules comprising an NSAID drug as a continuous phase.
International patent application WO 1994005260 to Affinity Biotech, inc. discloses a drug taste masking method that involves mixing a drug in particulate form into a lipid at a temperature below that at which significant drug degradation occurs, and adding an emulsifier, a polymer, and an aqueous dilution solution.
Despite the disclosures of the above patents and patent applications, there remains a need for methods of providing taste-masked propionic acid derivative compositions with reduced throat burning.
According to an embodiment of the present invention, propionic acid derivative particles were prepared as follows:
1. melting the propionic acid derivative and the wax while mixing;
2. dispersing the molten propionic acid derivative/wax mixture in hot water;
3. transferring the hot dispersion to another vessel containing ambient/cold water;
4. the dispersed droplets of propionic acid derivative/wax coagulate and form fine/spherical particles due to the rapid decrease in temperature;
5. the fine/spherical particles are filtered and dried.
The method of the present invention can be used to manufacture propionic acid derivative particles for pediatric and adult oral dosage forms. For example, the process of the invention may be used to make taste masked particles for use in chewable, powder, suspension, confectionery and/or orally disintegrating dosage forms.
In one embodiment, the particles of the present invention may be used in a liquid dosage form, such as a suspension. In embodiments in which a suspension dosage form is formed using the methods of the present invention, the particles may or may not be dried prior to incorporation into the suspension vehicle. In one embodiment of the suspension, the suspension is formed using the following process:
1. melting the propionic acid derivative and the wax while mixing;
2. dispersing the molten propionic acid derivative/wax mixture in hot water or in hot water containing a pharmaceutically preferred suspending agent (e.g. xanthan gum);
3. transferring the hot dispersion to another container containing an ambient/cold suspension vehicle;
4. the dispersed droplets of propionic acid derivative/wax coagulate and form fine/spherical particles due to the rapid decrease in temperature;
5. suspension is completed by the addition of excipients, sweeteners, preservatives and/or flavoring agents; according to another embodiment, a suspension is prepared by: the coagulated propionic acid/wax particles are isolated, dried and incorporated into the suspension by combining with excipients and water.
The preferred ratio of propionic acid derivative/wax for immediate release dosage forms is from about 80:20 to about 95: 5. A more preferred ratio of propionic acid derivative/wax for immediate release dosage forms is 85: 15.
The process of the present invention can also be used to manufacture propionic acid derivative particles for use in sustained release dosage forms. Suitable sustained release dosage forms include compressed tablets, capsules, liquid filled capsules, bilayer tablets. In one embodiment, the extended release coated particles of the present method may be blended with immediate release particles of a propionic acid derivative to form a dosage form having both immediate release and extended release characteristics. In another embodiment, the particles of the invention may be combined with additional active ingredients.
The preferred ratio of propionic acid derivative/wax for sustained release dosage forms is less than about 80: more than about 20 to about 40: 60. A more preferred ratio of propionic acid derivative/wax for a sustained release dosage form is from about 50:50 to about 70: 30. The preferred ratio of propionic acid derivative/wax for the sustained release dosage form is 70: 30. The preferred ratio of propionic acid derivative/wax for the sustained release dosage form is 50: 50.
The method of the present invention can be used to produce propionic acid derivative particles in the size range of about 50 microns to about 300 microns.
The process of the present invention can be used to produce propionic acid derivative particles having a narrow particle size range.
According to the present invention, the preferred propionic acid derivative is ibuprofen. Other propionic acid derivatives useful in the methods of the invention include, but are not limited to, ketoprofen and dexibuprofen.
Other features and advantages of the invention will be apparent from the description of the invention and from the claims.
Drawings
Figure 1 is a graph showing the dissolution of ibuprofen tablets containing taste masked ibuprofen particles with 15% glyceryl behenate and prepared according to the present invention.
Figure 2 is a graph showing the dissolution profiles of sustained release ibuprofen particles having 30% and 50% glyceryl behenate and prepared in accordance with the present invention.
Detailed Description
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Additionally, all publications, patent applications, patents, and sieve filtration references mentioned herein are incorporated by reference. As used herein, all percentages are by weight unless otherwise indicated. Moreover, all ranges shown herein are intended to encompass any combination of values between the two endpoints (inclusive of the recited endpoint).
As used herein, the term "immediate release" shall mean that the dissolution of the dosage form meets the United States Pharmacopeia (USP) specifications for immediate release tablets containing the particular active ingredient employed. For example, for ibuprofen tablets, USP 35 specifies that at least 80% of the ibuprofen contained in the dosage form is released within 60 minutes using USP apparatus 2 (paddle) in phosphate buffer at pH 7.2 at 50 rpm. See USP 35-NF 302012Ibuprofen Tablets Monograph and General Chapter <711> (Ibuprofen Tablets per treaty and Chapter 711).
Timed release technology (also known as sustained release) is a mechanism used in tablets or capsules to slowly dissolve and release drug over time. Sustained release tablets or capsules have the advantage that they can be taken less frequently than immediate release formulations of the same drug and that they maintain relatively stable levels of the drug in the bloodstream.
The term "good mouthfeel" shall refer to the general perception experienced by the consumer during and after oral administration of the following dosage forms, including but not limited to chewable dosage forms and/or suspensions.
The term "burning" should be understood to mean the pungent or pungent sensation typically perceived in the throat and/or mouth, which tends to be more pronounced with lower melting propionic acid derivatives such as ibuprofen and related compounds. This burning is different from bitter taste, as the addition of sweeteners is not effective in reducing this sensation. Cauterization may manifest itself as a irritative choking throat or a sudden cough.
Propionic acid derivatives are a well-known class of analgesic compounds. As used herein, propionic acid derivatives should be understood to include, but are not limited to, ibuprofen, naproxen, benzeneLoxfen, naproxen sodium, flurbiprofen, fenoprofen, fenprofen (fenbufoprofen), ketoprofen, indoprofen, pirprofen, carprofen (carpofen), oxaprofen (oxaprofen), pranoprofen, miroprofen (microprofen), sulfurLoxfen, suproprofen, alminoprofen, tiaprofenic acid, fluprofen and bucloxic acid. Structural formulae are shown in U.S. patent 4,923,898, which is hereby incorporated by reference. Propionic acid derivatives as defined herein are defined as having a free-CH (CH)3) COOH or-CH2CH2COOH or a pharmaceutically acceptable salt group (such as- -CH (CH)3) COO-Na + or CH2CH2COO — Na +) which is attached to the aromatic ring system, usually directly or via a carbonyl function.
Typical adult daily doses of the over the counter drug ibuprofen (a propionic acid derivative) are in the range of 200mg to 1200mg, and prescribed daily doses up to 3200 mg/day.
Ibuprofen is a widely used, well known non-steroidal anti-inflammatory propionic acid derivative. The chemical name of ibuprofen is 2- (4-isobutylphenyl) -propionic acid. As used herein, ibuprofen is understood to include 2- (4-isobutylphenyl) -propionic acid as well as pharmaceutically acceptable salts. Suitable ibuprofen salts include, but are not limited to, sodium, arginine, lysine, histidine and other salts as described, for example, in U.S. Pat. Nos. 4,279,926, 4,873,231, 5,424,075 and 5,510,385, the contents of which are incorporated herein by reference.
The formulations of the present invention may also contain pharmaceutically acceptable excipients, fillers, flavoring agents, diluents, lubricants, disintegrants, suspending agents, stabilizers, binders, colorants, carriers, and the like. For example, suitable carriers include lactose, starch, dicalcium phosphate, calcium sulfate, kaolin, mannitol, and powdered sugar. Typical binders include starch, gelatin, sugars (such as dextrose, mannitol, xylitol, sorbitol, maltodextrin, fructose, sucrose, molasses) and lactose, polyvinylpyrrolidone, polyethylene glycol, ethylcellulose and waxes. The lubricant comprises boric acid, sodium benzoate, magnesium stearate, sodium acetate, sodium chloride, leucine, polyethylene glycol, etc. Typical disintegrants include starches derived from wood, maize, potato and rice, methylcellulose, magnesium silicate, aluminum silicate, sucrose, dextrose, maltodextrin, agar, alginic acid, wood products, guar gum, citric acid syrup (citric pulp), sodium lauryl sulfate, and the like.
The present invention may be provided in liquid or semi-solid form, for example, elixirs, suspensions, syrups, gels, creams, ointments or creamy candies (sugar cream confection), such as fondant or nougat. Liquid or semi-solid formulations are prepared using manufacturing methods known in the art and pharmaceutically acceptable surfactants, dispersants, sweeteners, and diluents. Preferably, the present invention is provided in a tablet or other solid dosage form, and most preferably in a chewable dosage form.
The invention will now be illustrated by the following examples, but is not intended to be limited thereto. In the examples, it is to be understood that all parts are by weight unless otherwise indicated.
Examples of the invention
Specific embodiments of the present invention are illustrated by the following examples. The invention is not limited to the specific limitations shown in these examples.
Example 1: preparation of a pharmaceutical composition containing ibuprofen in a ratio of 85:15 drug to glyceryl behenate
Melted taste-masking particles of
Approximately 85g ibuprofen USP and 15g glyceryl behenate (which is commercially available as Comritol ATO 888 from Gattefose corporation in Lyon, France) were added to a suitable container while mixing with a laboratory mixer at a suitable speed and heated to 80-90 deg.C until the two ingredients melted. 200g of purified water was added to a second suitable stainless steel vessel and heated to about 80-90 deg.C. While mixing, the molten ibuprofen and glyceryl behenate mixture was added to the hot water. The dispersion of the molten mixture of ibuprofen and glyceryl behenate and hot water was then added to a separate container containing 200g of cold water (less than 10 ℃) while mixing to coagulate the ibuprofen/wax droplets. The resulting particles were filtered through a suitable stainless steel mesh, collected and dried overnight in a desiccator at room temperature. The resulting particles had an average particle size range between 170 and 250 microns.
Example 2: preparation of chewable tablets containing taste masked ibuprofen particles from example 1
The dried taste-masked ibuprofen granules from example 1 and the materials in the table below were blended together in a V-blender and then compressed to a hardness of 4-7kp using a rotary tablet press.
Table 1: formula of prototype ibuprofen chewable tablet
| Composition (I) | Percentages (weight/weight) |
| Containing ibuprofen (85% active substance)Melted taste-masking particles | 9.8 |
| Dextrose monohydrate | 83.2 |
| Crosslinked Povidone NF | 1.7 |
| Sweet orange flavoring agent | 0.3 |
| Magnesium stearate NF | 1.6 |
| Colloidal silica NF | 0.1 |
| Fumaric acid NF | 0.6 |
| Citric acid USP | 0.3 |
| FD&C yellow No. 6 aluminum lake | 0.2 |
| Acetylsulfanilic acid | 1.1 |
| Sucralose (NF) | 1.1 |
| Total of | 100.0 |
Example 3：Taste-masking cloths prepared with a 85:15 ratio of ibuprofen to glyceryl behenate Ibuprofen suspensions
The taste masked ibuprofen suspension was prepared in situ using the formulations in table 2. Ibuprofen and glyceryl behenate were melted in a 1500mL glass beaker "a" at 80-90 ℃. In beaker "B", citric acid and a portion of xanthan gum are dissolved in approximately 300mL of purified water heated to 80-90 ℃. The contents of beaker B were added to the molten ibuprofen/wax combination in beaker a with continuous stirring. The temperature of beaker A was maintained at 80-90 ℃. The water in section II was at room temperature, placed in a third beaker "C" and cooled to below 10 ℃. Once the ibuprofen and glyceryl behenate formed a uniform dispersion in water, the mixture was removed from the water bath and hot plate. The contents of beaker C were slowly poured into beaker a and continuously stirred at 1000-. Xanthan gum (from part III) was poured into glycerol and added to the mixture in beaker a. The remaining ingredients from part III were added to beaker a and mixed for 5 minutes. The resulting suspension is stored in a suitable labeled container.
TABLE 2: formulation of prototype ibuprofen suspension
| Composition (I) | Batches (g) |
| Part I | |
| Ibuprofen | 25.0 |
| Glyceryl behenate | 4.4 |
| Citric acid | 2.3 |
| Xanthan gum | 1.0 |
| Purified water | 300.0 |
| Part II | |
| Purified water | 362.5 |
| Section III | |
| Acetylsulfanilic acid | 1.3 |
| Corn starch | 18.8 |
| FD&C Red No. 40 | 0.1 |
| Cherry flavoring agent | 1.7 |
| Glycerol | 125.0 |
| Polysorbate 80 | 0.6 |
| Sodium benzoate | 2.5 |
| Sucralose | 0.7 |
| Sucrose | 375.0 |
| Xanthan gum | 1.3 |
| Total of | 1222.0 |
Example 4: preparation of a pharmaceutical composition comprising glyceryl behenate in a ratio of 70:30 and 50:50 drug
Sustained release particles of ibuprofen
Part A: 70:30 ratio of ibuprofen to glyceryl behenate
Approximately 70g ibuprofen USP (70 μm grade) and 30g glyceryl behenate (which is commercially available as Comritol ATO 888 from Gattefose corporation in Lyon, France) were added to a suitable container while mixing with a laboratory mixer at approximately 50RPM and heated to 80-90 ℃. 200g of purified water was added to a second suitable stainless steel vessel and heated to about 80-90 deg.C while mixing. The ibuprofen and glyceryl behenate mixture was added to hot water while mixing. The molten mixture of ibuprofen and glyceryl behenate and hot water were then added to a separate container containing 200g of cold water (less than 10 ℃) while mixing. The resulting particles were filtered through a 100 mesh stainless steel screen, collected, and dried at 30 ℃ for 6 hours. The resulting particles had an average particle size range between 170 and 250 microns.
And part B: 50:50 ratio of ibuprofen to glyceryl behenate
Approximately 50g ibuprofen USP (70 μm grade) and 50g glyceryl behenate (which is commercially available as Comritol ATO 888 from atteosse corporation in Lyon, France) were added to a suitable container while mixing with a laboratory mixer at approximately 50RPM and heated to 80-90 ℃. 200g of purified water was added to a second suitable stainless steel vessel and heated to about 80-90 ℃ while mixing. The ibuprofen and glyceryl behenate mixture was added to hot water while mixing. The molten mixture of ibuprofen and glyceryl behenate and hot water were then added to a separate container containing 200g of cold water (less than 10 ℃) while mixing. The resulting particles were filtered through a 100 mesh stainless steel screen, collected, and dried at 30 ℃ for 6 hours. The resulting particles had an average particle size range between 170 and 250 microns.
Example 5: alternative mixing method with 85:15 ratio of drug to glyceryl behenate
Preparation of melted taste-masked particles
Approximately 85g ibuprofen USP (70 μm grade) and 15g glyceryl behenate (which is commercially available as Comritol ATO 888 from Gattefose corporation in Lyon, France) were added to a suitable container while mixing with a laboratory mixer at approximately 50RPM and heated to 80-90 ℃. 200g of purified water preheated to 80-90 ℃ were added to the mixture while mixing. 200g of cold water (below 10 ℃) were then added to the same vessel while mixing. The resulting particles were filtered through a 100 mesh stainless steel screen, collected, and dried at 30 ℃ for 6 hours. The resulting particles had an average particle size range between 170 and 250 microns.
Example 6: dissolution of particles
The chewable tablets from example 2 (containing taste masked immediate release ibuprofen particles) were tested for dissolution using USP apparatus II. The dissolution medium was 900mL of pH 7.2 phosphate buffer with paddle speed 50 rpm. Dissolution data are shown in table 3 and figure 1. The dissolution of the sustained release ibuprofen particles from part a in example 4 (70:30 ibuprofen: glyceryl behenate) and part B in example 4 (50:50 ibuprofen: glyceryl behenate) was also analyzed, wherein the ibuprofen content was analyzed over a period of 10 hours using the same equipment relative to a standard prepared at 100% of theoretical concentration. Dissolution data are shown in table 4 and figure 2.
Table 3: dissolution analysis of chewable tablets prepared using taste masked ibuprofen particles
Table 4: dissolution analysis of sustained release ibuprofen particles
Claims (12)
1. A method of making propionic acid derivative particles, comprising:
melting the propionic acid derivative and the wax while mixing;
dispersing the molten propionic acid derivative/wax mixture in hot water;
transferring the hot propionic acid derivative/wax/water dispersion to another vessel containing cold water, wherein the dispersed droplets of propionic acid derivative/wax coagulate and form fine/spherical particles; and
the fine/spherical particles are filtered and dried.
2. The method of claim 1, wherein the propionic acid derivative is selected from the group consisting of: ibuprofen, naproxen and benzeneLoxfen, naproxen sodium, flurbiprofen, fenoprofen, fenprofen, ketoprofen, indoprofen, pirprofen, carprofen, oxaprofen, pranoprofen, carprofen, and sulfurLoxen, slpoprofen, alminoprofen, tiaprofenic acid, fluprofen and bucloxic acid.
3. The method of claim 1, wherein the wax is glyceryl behenate.
4. A method of manufacturing a dosage form comprising:
mixing the propionic acid derivative particles of claim 1 with a dosage form excipient; and
compressing the mixture into a dosage form.
5. Propionic acid derivative particles prepared by the process of claim 1.
6. A dosage form prepared by the process of claim 2.
7. A method of treatment comprising administering the dosage form of claim 6.
8. An immediate release pharmaceutical formulation comprising the propionic acid derivative particles of claim 5.
9. The immediate release pharmaceutical formulation of claim 8, wherein the formulation is a chewable tablet.
10. The immediate release pharmaceutical formulation of claim 8, wherein the formulation is an orally disintegrating tablet.
11. The immediate release pharmaceutical formulation of claim 8, wherein the propionic acid derivative particles comprise from about 80 parts propionic acid derivative/about 20 parts wax to about 95 parts propionic acid derivative/about 5 parts wax.
12. The immediate release pharmaceutical formulation of claim 9, wherein the propionic acid derivative particles comprise about 85 parts propionic acid derivative per about 15 parts wax.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261702392P | 2012-09-18 | 2012-09-18 | |
| US13/789,797 | 2013-03-08 | ||
| US13/789,797 US20140256810A1 (en) | 2013-03-08 | 2013-03-08 | Low melting propionic acid derivative particles for use in oral dosage forms |
| PCT/US2013/059918 WO2014047001A1 (en) | 2012-09-18 | 2013-09-16 | Low melting propionic acid derivative particles for use in oral dosage forms |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HK1209372A1 true HK1209372A1 (en) | 2016-04-01 |
Family
ID=49231643
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HK15110267.8A HK1209372A1 (en) | 2012-09-18 | 2013-09-16 | Low melting propionic acid derivative particles for use in oral dosage forms |
| HK16100781.5A HK1212886A1 (en) | 2012-09-18 | 2013-09-16 | Low melting propionic acid derivative particles for use in oral dosage forms |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HK16100781.5A HK1212886A1 (en) | 2012-09-18 | 2013-09-16 | Low melting propionic acid derivative particles for use in oral dosage forms |
Country Status (8)
| Country | Link |
|---|---|
| EP (1) | EP2897584A1 (en) |
| CN (1) | CN104640537A (en) |
| AU (1) | AU2013318356A1 (en) |
| BR (1) | BR112015005876A2 (en) |
| CA (1) | CA2884119A1 (en) |
| HK (2) | HK1209372A1 (en) |
| RU (1) | RU2015114540A (en) |
| WO (1) | WO2014047001A1 (en) |
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|---|---|---|---|---|
| RU2015110511A (en) * | 2014-03-28 | 2016-10-20 | МакНЕЙЛ-ППС, ИНК. | PARTICULAR DERIVATIVE ACID PARTICLES FOR DIRECT PRESS |
| CN109956860B (en) * | 2019-03-08 | 2022-03-01 | 天津大学 | A kind of preparation method of ibuprofen spherical crystal |
| WO2021104253A1 (en) * | 2019-11-25 | 2021-06-03 | 上海博志研新药物技术有限公司 | Ibuprofen pharmaceutical composition, preparation method therefor and use thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1497044A (en) | 1974-03-07 | 1978-01-05 | Prodotti Antibiotici Spa | Salts of phenyl-alkanoic acids |
| DE3440288C2 (en) | 1984-11-05 | 1987-03-12 | Gergely, Gerhard, Dr.-Ing., Wien | Pharmaceutical preparation containing ibuprofen and process for its preparation |
| US4923898A (en) | 1984-12-26 | 1990-05-08 | Analgesic Associates | Analgesic, anti-inflammatory and skeletal muscle relaxant compositions comprising non-steroidal anti-inflammatory drugs and musculoskeletal relaxants and methods of using same |
| US4873231A (en) | 1986-04-08 | 1989-10-10 | Smith Walton J | Decreasing the toxicity of an ibuprofen salt |
| CA2063141C (en) | 1989-08-04 | 1997-03-04 | Edward J. Roche | Rotogranulations and taste masking coatings for preparation of chewable pharmaceutical tablets |
| IT1246383B (en) | 1990-04-17 | 1994-11-18 | Eurand Int | METHOD FOR MASKING THE TASTE OF DRUGS |
| CA2061520C (en) | 1991-03-27 | 2003-04-22 | Lawrence J. Daher | Delivery system for enhanced onset and increased potency |
| US5405617A (en) | 1991-11-07 | 1995-04-11 | Mcneil-Ppc, Inc. | Aliphatic or fatty acid esters as a solventless carrier for pharmaceuticals |
| CA2143439A1 (en) | 1992-09-03 | 1994-03-17 | Seang H. Yiv | Taste-masking pharmaceutical compostiions and methods for making the same |
| IT1264855B1 (en) | 1993-06-21 | 1996-10-17 | Zambon Spa | PHARMACEUTICAL COMPOSITIONS CONTAINING S (+) - 2- (4-ISOBUTYLPHENYL) PROPIONIC ACID SALTS WITH BASIC AMINO ACIDS |
| ZA945944B (en) | 1993-08-13 | 1996-02-08 | Eurand America Inc | Procedure for encapsulating nsaids |
| TW442287B (en) | 1995-06-13 | 2001-06-23 | American Home Produits Corp | Organoleptically acceptable oral pharmaceutical composition comprising the S(+)1,8-diethyl-1-1,3,4,9-tetrahydropyrano[3,4-b] indole-1-acetic acid (Etodolac) |
| NZ333474A (en) | 1998-01-02 | 1999-06-29 | Mcneil Ppc Inc | A chewable tablet containing ibuprofen, fumaric acid and a non hydrocolloid binder e.g. a wax or a fat |
| US6117452A (en) | 1998-08-12 | 2000-09-12 | Fuisz Technologies Ltd. | Fatty ester combinations |
| FR2811912B1 (en) | 2000-07-21 | 2003-02-07 | Gattefosse Ets Sa | PROCESS FOR COATING SOLID PARTICLES WITH A HEAT-MELTING AGENT, AND SOLID PARTICLES THUS COATED |
| GB0113841D0 (en) | 2001-06-07 | 2001-08-01 | Boots Co Plc | Therapeutic agents |
| CA2548281C (en) * | 2003-12-09 | 2013-11-12 | Medcrystalforms, Llc | Method of preparation of mixed phase co-crystals with active agents |
| EP1845937A1 (en) * | 2004-12-10 | 2007-10-24 | Of Scientific & Industrial Research Council | Pharmaceutical composition for improving palatability of drugs and process for preparation thereof |
| BRPI0718428A2 (en) | 2006-10-25 | 2013-11-12 | Mcneil Ppc Inc | IBUPROPHEN COMPOSITION |
-
2013
- 2013-09-16 RU RU2015114540A patent/RU2015114540A/en not_active Application Discontinuation
- 2013-09-16 BR BR112015005876A patent/BR112015005876A2/en not_active IP Right Cessation
- 2013-09-16 AU AU2013318356A patent/AU2013318356A1/en not_active Abandoned
- 2013-09-16 CA CA2884119A patent/CA2884119A1/en not_active Abandoned
- 2013-09-16 EP EP13766453.8A patent/EP2897584A1/en not_active Withdrawn
- 2013-09-16 HK HK15110267.8A patent/HK1209372A1/en unknown
- 2013-09-16 WO PCT/US2013/059918 patent/WO2014047001A1/en not_active Ceased
- 2013-09-16 HK HK16100781.5A patent/HK1212886A1/en unknown
- 2013-09-16 CN CN201380048595.1A patent/CN104640537A/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| CA2884119A1 (en) | 2014-03-27 |
| BR112015005876A2 (en) | 2017-07-04 |
| WO2014047001A1 (en) | 2014-03-27 |
| EP2897584A1 (en) | 2015-07-29 |
| AU2013318356A1 (en) | 2015-03-19 |
| RU2015114540A (en) | 2016-11-10 |
| HK1212886A1 (en) | 2016-06-24 |
| CN104640537A (en) | 2015-05-20 |
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