The present invention relates to novel orally administered pharmaceutical compositions of Coenzyme Q10 and (3-Hydroxy (3-methylbutyric acid (HMB). It also relates to the process for the preparation of said compositions.
BACKGROUND OF THE INVENTION
Nutraceutical dosage forms are commonly used for their preventative and medicinal properties and facilitate preventing specific diseases and ailments.
The synergistic combination of essential nutritional supplements like Coenzyme Q10 and HMB is beneficial as nutritional supplement and expected to have various therapeutic uses.
Coenzyme Q10 is chemically known as 2,3-dimethoxy-5-methyl-6-decaprenyl-1,4-benzoquinone. Coenzyme Q10 plays various important functions such as energy production, membrane stabilization and antioxidant activity in the living body. The deficiency of Coenzyme Q10 is known to cause fatigue, hypertension and heart disease accordingly Coenzyme Q10 is believed to have significant health benefits for Central Nervous System (CNS), cardiovascular, diabetes and others disease conditions.
Another important known nutraceutical agent (3-Hydroxy (3-methylbutyric acid (HMB) is a metabolite of essential amino acid Leucine. HMB is important for protein synthesis in muscle cells and accordingly is an important ingredient for various nutritional supplement for building muscle mass. HMB is also known to have therapeutic use related to cardiovascular, diabetes and others disease conditions.
Japanese Patent Publication Number 2009153529, assigned to Tsujido Chemical Corp., discloses that HMB enhances the absorption of coenzyme Q10 in the body. The preferred compositions in general included Coenzyme Q10 and HMB in encapsulated form. The dosage form provided in the example is a soft gelatin capsule.

There are various technical challenges when preparing a dosage form with Coenzyme QIO and HMB. Coenzyme QIO is lipophilic and poorly soluble in water and its absorption after oral administration is low. On the other hand, HMB has a comparatively higher dose.
There is an unmet need of compositions of Coenzyme QIO and HMB.
The inventors of the present invention have prepared high drug load orally administered compositions of Coenzyme QIO and HMB which are expected to exhibit desired pharmaceutical technical attributes. The prepared compositions have nutraceutical and/or various therapeutic uses.
SUMMARY OF THE INVENTION
The present invention relates to high drug load orally administered pharmaceutical compositions of Coenzyme QIO and HMB.
One embodiment of the present invention relates to a pharmaceutical composition comprising Coenzyme QIO and HMB wherein the ratio of Coenzyme QIO and HMB is 1:0.01 w/w to 1:100 w/w and at least one pharmaceutically acceptable excipient.
Another embodiment of the present invention relates to a high drug load pharmaceutical composition comprising Coenzyme QIO and HMB and at least one pharmaceutically acceptable excipient.
Another embodiment of the present invention relates to a high drug load pharmaceutical powder composition comprising Coenzyme QIO and HMB and at least one pharmaceutically acceptable excipient.
Another embodiment of the present invention relates to a high drug load pharmaceutical powder composition for reconstitution comprising Coenzyme QIO and HMB and at least one pharmaceutically acceptable excipient.

Another embodiment of the present invention relates to a high drug load pharmaceutical tablet composition comprising Coenzyme QIO and HMB and at least one pharmaceutically acceptable excipient.
Another embodiment of the present invention relates to a high drug load pharmaceutical powder composition of Coenzyme QIO and HMB comprising two populations:
a) first population comprising from about 0.5% to about 80% w/w Coenzyme QIO and one or more pharmaceutically acceptable excipients, and
b) a second population comprising from about 1% to about 90% w/w HMB and one or more pharmaceutically acceptable excipients.
Another embodiment of the present invention relates to a high drug load pharmaceutical powder composition of Coenzyme QIO and HMB comprising two populations:
a) first population comprising from about 0.5% to about 80% w/w Coenzyme Q10 and one or more pharmaceutically acceptable excipients, and
b) a second population comprising from about 1% to about 90% w/w HMB and one or more pharmaceutically acceptable excipients,
wherein the first population is in the form of powder and second population is in the form of granules.
Another embodiment of the present invention relates to a high drug load pharmaceutical powder composition of Coenzyme Q10 and HMB comprising two populations:
a) first population comprising from about 0.5% to about 80% w/w Coenzyme Q10 and one or more pharmaceutically acceptable excipients, and
b) a second population comprising from about 1% to about 90% w/w HMB and one or more pharmaceutically acceptable excipients,

wherein the first population is in the form of granules and second population is in the form of granules.
Another embodiment of the present invention relates to a high drug load pharmaceutical powder composition of Coenzyme Q10 and HMB comprising two populations:
a) first population comprising from about 0.5% to about 80% w/w Coenzyme Q10 and one or more pharmaceutically acceptable excipients, and
b) a second population comprising from about 1% to about 90% w/w HMB and one or more pharmaceutically acceptable excipients,
wherein the first population is in the form of granules and second population is in the form of powder.
Another embodiment of the present invention relates to a high drug load pharmaceutical powder composition of Coenzyme Q10 and HMB comprising two populations:
a) first population comprising from about 0.5% to about 80% w/w Coenzyme Q10 and one or more pharmaceutically acceptable excipients, and
b) a second population comprising from about 1% to about 90% w/w HMB and one or more pharmaceutically acceptable excipients,
wherein the first population is in the form of powder and second population is in the form of powder.
Another embodiment of the present invention relates to a high drug load pharmaceutical powder composition of Coenzyme Q10 and HMB comprising:
a) about 0.5% to about 30% w/w Coenzyme Q10,
b) about 10% to about 90% w/w HMB,
c) about 10% to about 90% w/w diluent; and
d) one or more pharmaceutically acceptable excipients.

Another embodiment of the present invention relates to a high drug load pharmaceutical powder composition for reconstitution of Coenzyme QIO and HMB comprising:
a) about 0.5% to about 30% w/w Coenzyme QIO,
b) about 10% to about 90% w/w HMB,
c) about 0.05 to 10% w/w of suspending agent, and
d) one or more pharmaceutically acceptable excipients.
Another embodiment of the present invention relates to a high drug load pharmaceutical powder composition for reconstitution of Coenzyme Q10 and HMB comprising two populations:
a) first population comprising from about 0.5% to about 80% w/w Coenzyme Q10 and one or more pharmaceutically acceptable excipients, and
b) a second population comprising from about 1% to about 90% w/w HMB and one or more pharmaceutically acceptable excipients, and
c) about 0.05 to 10% w/w of suspending agent,
wherein the (i) first population is in the form of powder and second population is in the form of granules or (ii) first population is in the form of granules and second population is in the form of granules or (iii) first population is in the form of granules and second population is in the form of powder or (iv) first population is in the form of powder and second population is in the form of powder.
Another embodiment of the present invention relates to a high drug load pharmaceutical tablet composition of Coenzyme Q10 and HMB comprising:
a) about 0.5% to about 30% w/w Coenzyme Q10,
b) about 10% to about 90% w/w HMB, and
c) one or more pharmaceutically acceptable excipients.

Another embodiment of the present invention relates to a high drug load pharmaceutical tablet composition of Coenzyme Q10 and HMB comprising:
a) about 0.5% to about 30% w/w Coenzyme Q10,
b) about 10% to about 90% w/w HMB,
c) about 40% to about 60% diluent, and
d) about 0.1% to about 10% disintegrant.
Another embodiment of the present invention relates to a process of preparing high drug load pharmaceutical powder composition comprising:
(i) preparing powder or granules of Coenzyme Q10 with one or more pharmaceutically acceptable excipients by using formulation techniques selected from the group consisting of blending, wet granulation, dry granulation to form first population,
(ii) preparing powder or granules of HMB with one or more pharmaceutically acceptable excipients by using formulation techniques selected from the group consisting of blending, wet granulation, dry granulation to form second population,
(iii) mixing the powder or granules of Coenzyme Q10 of step (i) and powder or granules of HMB (ii), and
(iv) optionally lubricating the mixture of step (iii) to form the pharmaceutical powder composition.
Another embodiment of the present invention relates to a process of preparing high drug load pharmaceutical powder composition comprising:
(i) mixing Coenzyme Q10 and HMB with one or more pharmaceutically
acceptable excipients; and (ii) optionally lubricating the mixture of step (i) to form the pharmaceutical
powder composition.

Another embodiment of the present invention relates to a process of preparing high drug load pharmaceutical powder composition for reconstitution composition comprising:
(i) preparing powder or granules of Coenzyme Q10 with one or more pharmaceutically acceptable excipients by using formulation techniques selected from the group consisting of blending, wet granulation, dry granulation to form first population,
(ii) preparing powder or granules of HMB with one or more pharmaceutically acceptable excipients by using formulation techniques selected from the group consisting of blending, wet granulation, dry granulation to form the second population,
(iii) mixing the powder or granules of Coenzyme Q10 of step (i), powder or granules of HMB (ii) and suspending agent, and
(iv) optionally lubricating the mixture of step (iii) to form the pharmaceutical powder for reconstitution.
Another embodiment of the present invention relates to a process of preparing high drug load pharmaceutical powder composition for reconstitution composition comprising:
(iii) mixing Coenzyme Q10, HMB and suspending agent with one or more
pharmaceutically acceptable excipients; and (iv) optionally lubricating the mixture of step (i) to form the pharmaceutical
powder composition for reconstitution.
Another embodiment of the present invention relates to a process of preparing high drug load pharmaceutical tablet by direct compression or dry granulation or wet granulation or extrusion spheronization process.
Another embodiment of the present invention relates to a process of preparing high drug load pharmaceutical tablet composition comprising:

(i) mixing Coenzyme QIO and HMB with one or more pharmaceutically acceptable excipients;
(ii) granulating the mixture of step (i) using a solvent;
(iii) drying the granulated mixture of step (ii);
(iv) milling the mixture of step (iii) to form granules;
(v) lubricating the granules of step (iv); and
(vi) compressing the lubricated granules into a tablet.
Another embodiment of the present invention relates to a process of preparing high drug load pharmaceutical tablet composition comprising:
(i) mixing Coenzyme QIO and HMB with one or more pharmaceutically acceptable excipients;
(ii) compacting the mixture of step (i) to form slugs;
(iii) milling the slugs of step (ii) to form granules;
(v) lubricating the granules of step (iv); and
(vi) compressing the lubricated granules into a tablet.
Another embodiment of the present invention relates to a high drug load pharmaceutical composition comprising Coenzyme QIO and HMB and one or more pharmaceutically acceptable excipients for the treatment of cardiovascular diseases and diabetes.
DETAILED DESCRIPTION OF THE INVENTION
The present invention can be more readily understood by reading the following detailed description of the invention and study of the included examples. The term "composition" as used herein, is intended to encompass a pharmaceutical/nutraceutical product comprising Coenzyme QIO and HMB and/ or their pharmaceutically acceptable salts, esters, solvates, polymorphs,

stereoisomers or mixtures thereof, and other inert ingredient(s) (pharmaceutically acceptable excipients). Such pharmaceutical/nutraceutical compositions are synonymous with "formulation" and "dosage form". The compositions of the invention include, but are not limited to, granules, powder, powder for reconstitution into a solution or dispersion, tablet, capsules (hard capsules), soft gelatin capsules, sachets, microcapsules and the like. Particularly, the dosage form is granules/powder in a suitable pack such as sachet which can be administered as such or can be administered after reconstitution with a liquid medium such as water or a beverage such as fruit juice.
The term "high drug load" as used herein refers to a pharmaceutical/nutraceutical composition, wherein the composition comprises at least 40% w/w of the combination of Coenzyme Q10 and HMB based on the total weight of the composition. The composition comprises particularly from 40% w/w to 95% w/w of the combination of Coenzyme Q10 and HMB, particularly from 40% w/w to 90% w/w of the combination of Coenzyme Q10 and HMB, particularly from 40% w/w to 85% w/w of the combination of Coenzyme Q10 and HMB, particularly from 40% w/w to 80% w/w of the combination of Coenzyme Q10 and HMB, particularly from 40% w/w to 75% w/w of the combination of Coenzyme Q10 and HMB, and particularly from 40% w/w to 70% w/w of the combination of Coenzyme Q10 and HMB.
The term "excipient" as used herein refers to a pharmacologically inactive component such as a diluent, binder, disintegrant, glidant, lubricant, suspending agent, pH-regulating agent, surfactant, sweetener, flavoring agent, or the like. Co-processed excipients are also covered under the scope of present invention. The term "population" as used herein refers to powder or granules comprising active ingredient selected from HMB and/or Coenzyme Q10 with optionally one or more pharmaceutically acceptable excipients.
The term "about" means ± approximately 10% of the indicated value.

The term "substantially free of impurities" as used herein refers to a pharmaceutical composition of Coenzyme QIO and HMB wherein the composition contains less than 2% of total impurities.
The term "HMB" as used herein refers to 3-hydroxy-3-methylbutanoic acid and/or its pharmaceutically acceptable salts. It is also referred to as (3-hydroxy-(3-methylbutyricacid, or (3-hydroxy-isovaleric acid.
HMB can be in the form of a pharmaceutically acceptable salt such as calcium salt, sodium salt, potassium salt, ammonium salt and the like, or it can be in the form of HMB free acid. In particular, calcium HMB is used.
The maximum tolerated dose of Coenzyme QIO is 3 g/day. Usually it is given at a dose of up to 200 mg/day. According to Food Safety and Standards Authority of India (FSSAI), the maximum permitted dose range of HMB calcium is 3-6 g/day.
One embodiment of the present invention relates to a pharmaceutical composition comprising Coenzyme QIO and HMB, wherein the ratio of Coenzyme QIO and HMB is 1:0.01 w/w to 1:100 w/w and at least one pharmaceutically acceptable excipient.
The ratio of Coenzyme Q10 and HMB in the pharmaceutical composition of the present invention is 1:0.01 w/w to 1:100 w/w, particularly 1:0.1 w/w to 1:70 w/w, particularly l:0.1w/w to 1:60 w/w, particularly 1:0.1 w/w to 1:50 w/w, particularly 1:0.1 w/w to 1:40 w/w, particularly 1:0.1 w/w to 1:30 w/w, particularly 1:0.1 w/w to 1:20 w/w, particularly 1:0.1 w/w to 1:10 w/w, particularly 1:0.1 w/w to 1:5 w/w, particularly 1: 0.1 w/w to 1:3 w/w.
Another embodiment of the present invention relates to a high drug load pharmaceutical composition comprising Coenzyme Q10 and HMB and at least one pharmaceutically acceptable excipient.

Another embodiment of the present invention relates to a high drug load solid oral pharmaceutical composition comprising Coenzyme QIO and HMB and at least one pharmaceutically acceptable excipient.
Another embodiment of the present invention relates to a high drug load solid oral pharmaceutical composition selected from pharmaceutical powder composition, pharmaceutical powder composition for reconstitution, hard gelatin capsule and soft gelatin capsule comprising Coenzyme QIO and HMB and at least one pharmaceutically acceptable excipient.
Another embodiment of the present invention relates to a high drug load pharmaceutical powder composition comprising Coenzyme QIO and HMB and at least one pharmaceutically acceptable excipient.
Another embodiment of the present invention relates to a high drug load pharmaceutical powder composition for reconstitution into a dispersion comprising Coenzyme QIO and HMB and at least one pharmaceutically acceptable excipient.
Another embodiment of the present invention relates to a high drug load pharmaceutical tablet comprising Coenzyme QIO and HMB and at least one pharmaceutically acceptable excipient.
Another embodiment of the present invention relates to a high drug load pharmaceutical powder composition of Coenzyme QIO and HMB comprising two populations:
a) first population comprising from about 0.5% to about 80% w/w Coenzyme QIO and one or more pharmaceutically acceptable excipients, and
b) a second population comprising from about 1% to about 90% w/w HMB and one or more pharmaceutically acceptable excipients.

Another embodiment of the present invention relates to a high drug load pharmaceutical powder composition of Coenzyme Q10 and HMB comprising two populations:
a) first population comprising from about 0.5% to about 80% w/w Coenzyme Q10 and one or more pharmaceutically acceptable excipients, and
b) a second population comprising from about 1% to about 90% w/w HMB and one or more pharmaceutically acceptable excipients,
wherein the first population is in the form of powder and second population is in the form of granules.
Another embodiment of the present invention relates to a high drug load pharmaceutical powder composition of Coenzyme Q10 and HMB comprising two populations:
a) first population comprising from about 0.5% to about 80% w/w Coenzyme Q10 and one or more pharmaceutically acceptable excipients, and
b) a second population comprising from about 1% to about 90% w/w HMB and one or more pharmaceutically acceptable excipients,
wherein the first population is in the form of granules and second population is in the form of granules.
Another embodiment of the present invention relates to a high drug load pharmaceutical powder composition of Coenzyme Q10 and HMB comprising two populations:
a) first population comprising from about 0.5% to about 80% w/w Coenzyme Q10 and one or more pharmaceutically acceptable excipients, and
b) a second population comprising from about 1% to about 90% w/w HMB and one or more pharmaceutically acceptable excipients,
wherein the first population is in the form of granules and second population is in the form of powder.

Another embodiment of the present invention relates to a high drug load pharmaceutical powder composition of Coenzyme Q10 and HMB comprising two populations:
a) first population comprising from about 0.5% to about 80% w/w Coenzyme Q10 and one or more pharmaceutically acceptable excipients, and
b) a second population comprising from about 1% to about 90% w/w HMB and one or more pharmaceutically acceptable excipients,
wherein the first population is in the form of powder and second population is in the form of powder.
Another embodiment of the present invention relates to a high drug load pharmaceutical powder for reconstitution of Coenzyme Q10 and HMB comprising:
a) about 0.5% to about 30% w/w Coenzyme Q10,
b) about 10% to about 90% w/w HMB,
c) about 0.05 to 10% w/w of suspending agent; and
d) one or more pharmaceutically acceptable excipients.
Another embodiment of the present invention relates to a high drug load pharmaceutical powder for reconstitution of Coenzyme Q10 and HMB comprising:
a) about 0.5% to about 30% w/w Coenzyme Q10,
b) about 10% to about 90% w/w HMB and one or more pharmaceutically
acceptable excipients,
c) about 0.05 to 10% w/w of suspending agent; and
d) one or more pharmaceutically acceptable excipients, wherein the composition is free from binder and/or disintegrant.

Another embodiment of the present invention relates to a high drug load pharmaceutical tablet composition of Coenzyme Q10 and HMB comprising:
a) about 0.5% to about 30% w/w Coenzyme Q10,
b) about 10% to about 90% w/w HMB, and
c) one or more pharmaceutically acceptable excipients.
Another embodiment of the present invention relates to a high drug load pharmaceutical tablet of Coenzyme Q10 and HMB comprising:
a) about 0.5% to about 30% w/w Coenzyme Q10,
b) about 10% to about 90% w/w HMB,
c) about 40% to about 60% w/w diluent, and
d) about 0.1% to about 10% w/w disintegrant.
Another embodiment of the present invention relates to a process of preparing high drug load pharmaceutical powder composition comprising:
(i) preparing powder or granules of Coenzyme Q10 with one or more pharmaceutically acceptable excipients by using formulation techniques selected from the group consisting of blending, wet granulation, dry granulation to form first population,
(ii) preparing powder or granules of HMB with one or more pharmaceutically acceptable excipients by using formulation techniques selected from the group consisting of blending, wet granulation, dry granulation to form the second population,
(iii) mixing the powder or granules of Coenzyme Q10 of step (i) and powder or granules of HMB (ii), and
(iv) optionally lubricating the mixture of step (iii) to form the pharmaceutical powder composition.

Another embodiment of the present invention relates to a process of preparing high drug load pharmaceutical powder composition comprising:
(v) mixing Coenzyme Q10 and HMB with one or more pharmaceutically
acceptable excipients; and (vi) optionally lubricating the mixture of step (i) to form the
pharmaceutical powder composition.
Another embodiment of the present invention relates to a process of preparing high drug load pharmaceutical powder composition for reconstitution composition comprising:
(i) preparing powder or granules of Coenzyme Q10 with one or more pharmaceutically acceptable excipients by using formulation techniques selected from the group consisting of blending, wet granulation, dry granulation to form first population,
(ii) preparing powder or granules of HMB with one or more pharmaceutically acceptable excipients by using formulation techniques selected from the group consisting of blending, wet granulation, dry granulation to form the second population,
(iii) mixing suspending agent, powder or granules of Coenzyme Q10 of step (i) and powder or granules of HMB (ii), and
(iv) optionally lubricating the mixture of step (iii) to form the pharmaceutical powder for reconstitution.
Another embodiment of the present invention relates to a process of preparing high drug load pharmaceutical powder composition for reconstitution composition comprising:
(v) mixing Coenzyme Q10, HMB and suspending agent with one or more
pharmaceutically acceptable excipients; and (vi) optionally lubricating the mixture of step (i) to form the powder
composition for reconstitution.

Another embodiment of the present invention relates to a process of preparing a high drug load pharmaceutical powder composition or a high drug load pharmaceutical powder composition for reconstitution by spray drying technique. An aqueous slurry of HMB and one or more pharmaceutically acceptable excipients is prepared by dissolving HMB and one or more pharmaceutically acceptable excipients in water. The slurry is spray dried and optionally mixed with one or more excipients to obtain HMB powder.
Another embodiment of the present invention relates to a process of preparing high drug load pharmaceutical tablet composition by direct compression or dry granulation or wet granulation or extrusion spheronization process.
Another embodiment of the present invention relates to a process of preparing high drug load pharmaceutical tablet composition comprising:
(i) mixing Coenzyme Q10 and HMB with one or more pharmaceutically acceptable excipients;
(ii) granulating the mixture of step (i) using a solvent;
(iii) drying the granulated mixture of step (ii);
(iv) milling the mixture of step (iii) to form granules;
(v) lubricating the granules of step (iv); and
(vi) compressing the lubricated granules into a tablet.
Another embodiment of the present invention relates to a process of preparing high drug load pharmaceutical tablet composition comprising:
(i) mixing Coenzyme Q10 and HMB with one or more pharmaceutically acceptable excipients;
(ii) compacting the mixture of step (i) to form slugs;
(iii) milling the slugs of step (ii) to form granules;
(v) lubricating the granules of step (iv); and

(vi) compressing the lubricated granules into a tablet.
Another embodiment of the present invention relates to a high drug load pharmaceutical composition comprising Coenzyme QIO and HMB and at least one pharmaceutically acceptable excipient, wherein the composition is substantially free of impurities.
Coenzyme QIO can be complexed with cyclodextrin before incorporation into the composition. Coenzyme QIO can also be dissolved in a solvent/solubilizer and adsorbed onto diluent such as microcrystalline cellulose before incorporation into the composition.
The pharmaceutical powder composition or pharmaceutical powder composition for reconstitution into a dispersion can be prepared by any process known in the art such as dry blending or by granulation technique such as dry granulation and wet granulation, and spray drying.
The pharmaceutical powder for reconstitution for oral suspension can be reconstituted using water. It can also be reconstituted by admixing with a liquid beverage such as fruit juice before administration.
Diluents or fillers are substances which usually provide bulk to the composition. Various useful fillers or diluents include, but are not limited to calcium carbonate, calcium phosphate, dibasic anhydrous, calcium phosphate, dibasic dihydrate, calcium phosphate tribasic, calcium sulphate, cellulose powdered, silicified microcrystalline cellulose, cellulose acetate, lactitol, lactose, mannitol, magnesium carbonate, magnesium oxide, maltodextrin, mannitol, microcrystalline cellulose, polydextrose, simethicone, sodium alginate, sodium chloride, sorbitol, starch, pregelatinized starch, and xylitol, or mixtures thereof. The diluent may constitutes from about 10 to about 95% by weight the composition

Binders impart cohesiveness to formulation. Various useful binders include, but are not limited to hydroxypropylmethyl cellulose, hydroxypropyl cellulose, acacia, alginic acid, carbomer, carboxymethylcellulose sodium, ceratonia, dextrin, dextrose, gelatin, guar gum, hydroxyethyl cellulose, hydroxyethyhnethyl cellulose, magnesium aluminium silicate, maltodextrin, maltose, methylcellulose, polydextrose, polyethylene oxide, polymethacrylates, polyvinylpyrrolidone (povidone), sodium alginate, starch, pregelatinized starch, stearic acid, sucrose and zein, or mixtures thereof.
Examples of water insoluble binders includes cellulose derivatives (e.g. ethylcellulose), polyvinyl acetate (Kollicoat SR30D), phthalate based polymers and copolymers, neutral copolymers based on ethyl acrylate and methylmethacrylate, copolymers of acrylic and methacrylic acid esters, and with quaternary ammonium groups, such as Eudragit NE, Eudragit RS, Eudragit RS30D, Eudragit RL and Eudragit RL30D, or mixtures thereof. Water swellable binders may also be used to achieve the pharmaceutical compositions of the present invention. The binders may constitutes from about 0% to about 20% by weight of the composition.
Various useful disintegrants include, but are not limited to, alginic acid, calcium phosphate, tribasic, carboxymethylcellulose calcium, carboxymethylcellulose sodium, colloidal silicon dioxide, croscarmellose sodium, crospovidone, docusate sodium, guar gum, low substituted hydroxypropyl cellulose, magnesium aluminun silicate, methylcellulose, microcrystalline cellulose, povidone, sodium alginate, sodium starch glycolate, polacrilin potassium, silicified microcrystalline cellulose, starch or pre- gelatinized starch, or mixtures thereof. Disintegrants constitute from about 0% to about 20% by weight the composition.
Glidants improve flowability and accuracy of dosing. Glidants used in the composition include, but are not limited to, tribasic calcium phosphate, calcium silicate, cellulose, powdered, colloidal silicon dioxide, magnesium silicate,

magnesium trisilicate, starch and talc or mixtures thereof. Glidants constitute from about 0% to about 5% by weight the composition.
Various useful lubricants include, but are not limited to, magnesium stearate, calcium stearate, stearic acid, zinc stearate, sucrose stearate, silicon dioxide, hydrogenated vegetable oil, talc, poloxamer, adipic acid, glyceryl palmitostearate, glycerine monostearate, medium-chain triglycerides, sodium stearyl fumarate, glyceryl behenate, sodium lauryl sulphate, sodium stearyl fumarate, magnesium lauryl sulphate and polyethylene glycol. Lubricants are present in the range from about 0.1% to about 5% w/w of the composition.
Various useful suspending agents include, but are not limited to, cellulose derivatives such as hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, methylcellulose, carboxymethyl cellulose and its salts/derivatives e.g., carboxymethyl cellulose sodium, microcrystalline cellulose, and co-processed spray dried forms of microcrystalline cellulose and carboxymethyl cellulose sodium (such as Avicel® RC-501, Avicel® RC-581, Avicel® RC-591, and Avicel® CL-611); carbomers (such as those available under the trade name Carbopol); gums such as xanthan gum, locust bean gum, tragacanth gum, arabinogalactan gum, agar gum, gellan gum, guar gum, apricot gum, karaya gum, sterculia gum, acacia gum, gum arabic, and carrageenan; pectin; propylene glycol alginate, dextran; gelatin; polyethylene glycols; polyvinyl compounds such as polyvinyl acetate, polyvinyl alcohol, and polyvinyl pyrrolidone; sugar alcohols such as xylitol and mannitol; colloidal silica; maltodextrin, starch; alginic acid, and mixtures thereof. Suspending agent constitute from about 0.01% to about 10% by weight of the composition.
Various useful pH regulating agents or buffering agents include, but are not limited to, citrate buffers, phosphate buffers, or any other suitable buffer known in the art including monosodium dibasic phosphate, gluconic acid, lactic acid, citric acid, acetic acid, sodium gluconate, sodium lactate, sodium citrate, sodium acetate

potassium citrate, sodium bicarbonate, potassium bicarbonate, sodium dihydrogen phosphate and potassium dihydrogen phosphate.
Various useful sweetening agents include, but are not limited to, sugar or a sugar alcohol such as sucrose, dextrose, sucralose, sorbitol, fructose, mannitol and invert sugar and sugar substitutes such as saccharin sodium, aspartame.
Various useful flavoring agents, include, but are not limited to, flavors such as banana, lemon, orange, grape, lime and grapefruit, vanilla, and fruit essence, including apple, banana, pear, peach, strawberry, raspberry, cherry, plum, pineapple, apricot; synthetic flavor oils and flavoring aromatics and/or natural oils, extracts from plant leaves, flowers, fruits such as cinnamon oil, oil of wintergreen, peppermint oils, clove oil, citrus oil, bay oil, anise oil, eucalyptus, thyme oil, cedar leaf oil, oil of nutmeg, oil of sage, oil of bitter almonds, and cassia oil; maltol, ethyl vanillin, menthol, citric acid, fumaric acid, ethyl maltol, and tartaric acid and combinations thereof.
Surfactants or surface-active agents improve wettability of the dosage form and/or enhance its dissolution. Surfactants contemplated in the present invention include but are not limited to anionic surfactants, amphoteric surfactants, non-ionic surfactants and macromolecular surfactants. Suitable examples of anionic surfactants include but are not limited to sodium lauryl sulphate, sodium cetyl stearyl sulphate or sodium dioctyl sulphosuccinate etc. Suitable example of an amphoteric surfactant include but is not limited to lecithin. Suitable examples of non-ionic surfactants include but is not limited to cetyl alcohol, stearyl alcohol, cetyl stearyl alcohol, cholesterol, sorbitan fatty acid esters such as sorbitan mono-oleate, polyoxyethylene sorbitan fatty acid esters such as polysorbate 20, polyoxyethylene fatty acid glycerides such as macrogol 1000 glycerol monostearate, polyoxyethylene fatty acid esters such as polyoxyl 40 stearate, polyoxyethylene fatty alcohol ethers such as polyoxyl 10 oleyl ether, glycerol fatty acid esters such as glycerol monostearate, commercially available Sepitrap®

80 or Sepitrap 4000 etc. Surfactant constitute from about 0% to about 5% by weight of the composition.
Various useful solvents include, but are not limited to, water, esters such as ethyl acetate; ketones such as acetone; alcohols such as methanol, ethanol, isopropanol, butanol; dichloromethane, chloroform, dimethyl acetamide (DMA), dimethyl sulfoxide (DMSO), ether, diethyl ether and combinations thereof.
The Coenzyme Q10 and HMB compositions of the present invention can
optionally include at least one of carbohydrate, fat, protein, minerals or any other
nutrient.
The Coenzyme Q10 and HMB powder compositions and powder for
reconstitution of the present invention can be packaged in a suitable pack such as
sachet, stick pack, plastic or metal container. The tablet can be packaged in a
suitable pack such as blister pack and bottle pack.
The invention may be further illustrated by the following examples, which are for
illustrative purposes only and should not be construed as limiting the scope of the
invention in any way.
EXAMPLES Examples 1-4. Coenzyme Q10 + HMB Powder

Example No. 1 2 3 4
First Population (% w/w)
Ingredients Granules Granules Powder Powder
Coenzyme Q10 5-30 5-30 5-30 5-30
Sorbitol 20-90 20-90 20-90 20-90
Sodium Citrate 0-5% 0-5% 0-5% 0-5%
Saccharin sodium 0-3% 0-3% 0-3% 0-3%
Isopropyl alcohol and water q.s. q.s. - q.s.
Sodium Benzoate 0-3% 0-3% 0-3% 0-3%
Flavor 0-3% 0-3% 0-3% 0-3%
Second Population (% w/w)

Ingredients Granules Powder Powder Granules
HMB 40-90 40-90 40-90 40-90
Microcrystalline cellulose 30-60 30-60 30-60 30-60
Polyvinylpyrrolidone 0-3% 0-3% 0-3% 0-3%
Isopropyl alcohol and water q.s. - - q.s.
Extra Components (% w/w)
Strawberry flavor 0-1 0-1 0-1 0-1
Magnesium stearate 0.1-2 0.1-2 0.1-2 0.1-2
Procedure:
1. First population of Coenzyme Q10 and second population of HMB is prepared by Dry blending/Dry granulation/Wet granulation. In case of wet granulation, mixture of isopropyl alcohol and water is used.
2. First population of Coenzyme Q10, second population of HMB, strawberry flavour and magnesium stearate are mixed to form Coenzyme Q10 and HMB powder composition.
Example 5. Coenzyme Q10 + HMB Granule

Ingredients % w/w
Coenzyme Q10 + HMB 40-90
Microcrystalline cellulose/ Maltodextrin 30-60
Silicon dioxide 0.5
Citric acid 1
Sucrose 10
Strawberry flavor 1
Procedure:
1. Coenzyme Q10, HMB, citric acid, sucrose, microcrystalline
cellulose/maltodextrin, and strawberry flavour are mixed.
2. The mixture of step 1 is lubricated with silicon dioxide.

Example 6. Coenzyme QIO + HMB Powder

Ingredients % w/w
Coenzyme QIO + HMB 40-90
Polyvinylpyrrolidone 1
Microcrystalhne cellulose 30-60
Silicon dioxide 0.5
Citric acid 0.5
Sucrose 10
Croscarmellose sodium 6
Strawberry flavor 1
Water q.s.
Procedure:
1. Coenzyme Q10, HMB, citric acid, sucrose and croscarmellose sodium are
mixed.
2. Polyvinylpyrrolidone is dissolved in water to form a solution.
3. The mixture of step 1 is granulated with the solution of step 2.
4. The granules of step 3 are mixed with microcrystalhne cellulose and strawberry flavour.
5. The mixture of step 4 is lubricated with silicon dioxide and filled into a sachet.
Examples 7-10. Coenzyme Q10 + HMB Powder for Reconstitution

Example No. 7 8 9 10
First Population (% w/w)
Ingredients Granules Granules Powder Powder
Coenzyme Q10 5-30 5-30 5-30 5-30
Sorbitol 20-90 20-90 20-90 20-90
Sodium Citrate 0-5% 0-5% 0-5% 0-5%
Saccharin sodium 0-3% 0-3% 0-3% 0-3%
Isopropyl alcohol and water q.s. q.s. - q.s.
Sodium Benzoate 0-3% 0-3% 0-3% 0-3%
Flavor 0-3% 0-3% 0-3% 0-3%
Second Population (% w/w)
Ingredients Granules Powder Powder Granules

HMB 40-90 40-90 40-90 40-90
Microcrystalline cellulose 30-60 30-60 30-60 30-60
Polyvinylpyrrolidone 0-3% 0-3% 0-3% 0-3%
Isopropyl alcohol and water q.s. - - -
Suspending Agent (% w/w)
Xanthan gum 0.01-5% 0.01-5% 0.01-5% 0.01-5%
Extra Components (% w/w)
Strawberry flavor 0-1 0-1 0-1 0-1
Magnesium stearate 0.1-2 0.1-2 0.1-2 0.1-2
Procedure:
1. First population of Coenzyme Q10 and second population of HMB is prepared by Dry blending/Dry granulation/Wet granulation. In case of wet granulation, mixture of isopropyl alcohol and water is used.
2. The first population of Coenzyme Q10, second population of HMB, and xanthan gum, strawberry flavour and magnesium stearate are mixed to form powder for reconstitution.
The powder for reconstitution can be reconstituted into a dispersion with water before administration.
Example 11. Coenzyme O10 + HMB Tablet

Ingredients % w/w
Coenzyme Q10 + HMB 40-90
Polyvinylpyrrolidone 1
Microcrystalline cellulose 30-60
Citric acid 0.5
Sucrose 10
Croscarmellose sodium 6
Magnesium stearate 1
Water q.s.
Procedure:
1. Coenzyme Q10, HMB, citric acid, sucrose and croscarmellose sodium are mixed.

2. Polyvinylpyrrolidone is dissolved in water to form a solution.
3. The mixture of step 1 is granulated with the solution of step 2.
4. The granules of step 3 are mixed with microcrystalline cellulose.
5. The mixture of step 4 is lubricated with magnesium stearate and compressed into a tablet.

We Claim:

1.A high drug load pharmaceutical powder composition of Coenzyme Q10 and
HMB comprising two populations:
a) first population comprising from about 0.5% to about 80% w/w Coenzyme Q10 and one or more pharmaceutically acceptable excipients, and
b) a second population comprising from about 1% to about 90% w/w HMB and one or more pharmaceutically acceptable excipients.

2. The pharmaceutical powder composition of claim 1, wherein the first population is in the form of powder and second population is in the form of granules.
3. The pharmaceutical powder composition of claim 1, wherein the first population is in the form of granules and second population is in the form of granules.
4. The pharmaceutical powder composition of claim 1, wherein the first population is in the form of powder and second population is in the form of powder, or the first population is in the form of granule and second population is in the form of powder.
5. A high drug load pharmaceutical powder composition of Coenzyme Q10 and
HMB comprising:
a) about 0.5% to about 30% w/w Coenzyme Q10,
b) about 10% to about 90% w/w HMB,
c) about 10% to about 90% w/w diluent; and
d) one or more pharmaceutically acceptable excipients.
6. A high drug load pharmaceutical powder composition for reconstitution of
Coenzyme Q10 and HMB comprising:
a) about 0.5% to about 30% w/w Coenzyme Q10,

b) about 10% to about 90% w/w HMB,
c) about 0.05% to 10% w/w of suspending agent; and
d) one or more pharmaceutically acceptable excipients

7. The pharmaceutical composition of claims 1, 5 or 6, wherein the one or more pharmaceutically acceptable excipients are selected from the group comprising diluent, binder, disintegrant, glidant, lubricant, suspending agent, pH-regulating agent, surfactant, sweetener and flavoring agent.
8. The pharmaceutical powder composition of claims 1, 5 or 6, wherein the composition is free from binder and/or disintegrant.
9. A high drug load pharmaceutical tablet composition of Coenzyme Q10 and
HMB comprising:
a) about 0.5% to about 30% w/w Coenzyme Q10,
b) about 10% to about 90% w/w HMB,
c) about 40% to about 60% w/w diluent, and
d) about 0.1 w/w to about 10% w/w disintegrant.
10. A process of preparing pharmaceutical powder composition of claim 1 and
claim 5 or pharmaceutical powder composition for reconstitution of claim 6
comprising preparing powder or granules of Coenzyme Q10 and pharmaceutically
acceptable excipients by using formulation techniques selected from the group
consisting of blending, wet granulation, dry granulation to form first population
and preparing powder or granules of HMB and pharmaceutically acceptable
excipients by using formulation techniques selected from the group consisting of
blending, wet granulation, dry granulation to form the second population to form
the pharmaceutical powder composition and further mixing with a suspending
agent to form pharmaceutical powder for reconstitution.