Lacosamide pharmaceutical composition as well as preparation method and applications thereof
A lacosamide pharmaceutical composition as well as a preparation method and application thereof are provided. According to the lacosamide pharmaceutical composition, lacosamide or a pharmaceutically acceptable salt thereof can be dissolved out at the same time, wherein the dissolution rate of the lacosamide pharmaceutical composition is not more than 40% within 1 hour, the dissolution rate of the lacosamide pharmaceutical composition is 20-70% within 6 hours, and the dissolution rate of the lacosamide pharmaceutical composition is not less than 65% within 24 hours. The lacosamide pharmaceutical composition has good slow release performance, the tablet size can be rapidly expanded in the in-vitro dissolution process, the expanded lacosamide pharmaceutical composition has good rigidity and elasticity and has a remarkable retention effect in the stomach, and the cumulative release rate within 24 hours can reach 80% or above.
1 . A pharmaceutical composition, wherein the pharmaceutical composition is a 24-hour sustained-release gastro-retentive tablet comprising an active pharmaceutical ingredient, a skeleton material, a swelling material and a disintegrant,
wherein the active pharmaceutical ingredient is lacosamide or a pharmaceutically acceptable salt of lacosamide, and the weight percentage of the active pharmaceutical ingredient is 5.0%-40.0%,
the skeleton material is selected from one or more of a polyvinyl acetate povidone mixture, sodium alginate, and hydroxypropyl methylcellulose,
when the skeleton material is the polyvinyl acetate povidone mixture, the polyvinyl acetate povidone mixture comprises polyvinyl acetate povidone (PVAc) and polyvinylpyrrolidone (PVP) in a weight ratio of 80:19 and has a weight percentage of 18.36%-24.68%,
when the skeleton material is the sodium alginate, the skeleton material has a weight percentage of 5%-35.09%,
when the skeleton material is the hydroxypropyl methylcellulose, the skeleton material has a weight percentage of 8%-17.27%;
the swelling material is selected from one or two of polyoxyethylene and carbomer, and the weight percentage of the swelling material is 1.0%-60.0%;
the disintegrant is selected from one or more of crospovidone, sodium carboxymethyl starch, croscarmellose sodium, carboxymethylcellulose calcium, and low-substituted hydroxypropylcellulose, and the weight percentage of the disintegrant is 5%-30.0%; and
under the United States Pharmacopeia (USP) dissolution apparatus method 2 that uses 900 mL of 0.1N hydrochloric acid at 50 rpm, or uses 900 mL of an acetate buffer with a pH of 4.5 at 50 rpm, dissolution of the pharmaceutical composition simultaneously satisfies the following three criteria:
A) no more than 40% of the active pharmaceutical ingredient is dissolved within 1 hour;
B) 20%-70% of the active pharmaceutical ingredient is dissolved within 6 hours; and
C) no less than 65% of the active pharmaceutical ingredient is dissolved within 24 hours.
2 . The pharmaceutical composition of claim 1 , wherein:
when the swelling material is polyoxyethylene, the swelling material has a weight percentage of 15%-20%;
when the swelling material is the carbomer, the swelling material has a weight percentage of 3%-6%; and
under the USP method of dissolution apparatus method 2, dissolution of the pharmaceutical composition satisfies:
no more than 30% of the active pharmaceutical ingredient is dissolved within 1 hour;
30%-55% of the active pharmaceutical ingredient is dissolved within 6 hours; and
no less than 80% of the active pharmaceutical ingredient is dissolved within 24 hours.
3 . The pharmaceutical composition as claimed in claim 1 ,
further comprising one or more components selected from a skeleton strength regulator, a diluent, and a lubricant,
wherein the skeleton strength regulator is selected from dicalcium phosphate and dicalcium phosphate dihydrate;
the weight percentage of the skeleton regulator is 10%-15.0%;
the diluent is one or more selected from dextrose, lactose monohydrate, anhydrous lactose, sucrose, mannitol, xylitol, sorbitol, microcrystalline cellulose, starch, pregelatinized starch, dicalcium phosphate dihydrate, anhydrous dicalcium phosphate, and cyclodextrin or a derivative thereof; and the weight percentage of the diluent is 10%-40%;
the lubricant is one or more selected from talc, stearic acid, metal stearate, stearate ester, colloidal silica, glyceryl behenate, sodium lauryl sulfate, hydrogenated vegetable oil, mineral oil, poloxamer, polyethylene glycol, and sodium chloride; and the weight percentage of the lubricant is 0.5%-2.0%.
4 . The pharmaceutical composition as claimed in claim 1 , selected from formula one, formula two, formula three, formula four, formula five, and formula six, wherein:
the formula one comprises: 18.18% lacosamide, 35.09% sodium alginate, 13.64% crospovidone, 11.73% anhydrous dicalcium phosphate, 1.10% magnesium stearate, 3.00% carbomer, and 17.27% hydroxypropyl methylcellulose;
the formula two comprises: 20.00% lacosamide, 24.80% polyvinyl acetate povidone mixture, 20.00% crospovidone, 1.20% magnesium stearate, 20.00% sorbitol, 6.00% carbomer, and 8.00% hydroxypropyl methylcellulose;
the formula three comprises: 18.18% lacosamide, 35.09% sodium alginate, 16.64% crospovidone, 16.73% hydroxypropyl methylcellulose, 0.55% colloidal silica, 1.10% magnesium stearate, and 11.73% anhydrous dicalcium phosphate;
the formula four comprises: 18.18% lacosamide, 35.09% sodium alginate, 16.64% crospovidone, 16.73% polyoxyethylene, 0.55% colloidal silica, 1.10% magnesium stearate, and 11.73% anhydrous dicalcium phosphate;
the formula five comprises: 18.18% lacosamide, 25.45% sodium alginate, 16.36% crospovidone, 0.55% colloidal silica, 1.10% magnesium stearate, 9.09% hydroxypropyl methylcellulose, 18.36% polyvinyl acetate povidone mixture, and 10.91% dicalcium phosphate dihydrate; and
the formula six comprises: 20.00% lacosamide, 24.80% polyvinyl acetate povidone mixture, 20.00% crospovidone, 1.20% magnesium stearate, 15.00% sorbitol, 5.00% sodium alginate, 6.00% carbomer, and 8.00% hydroxypropyl methylcellulose.
5 . A preparation method for the pharmaceutical composition as claimed in claim 1 , comprising a dry granulation process.
6 . A method for treating and/or preventing acute and chronic pain, comprising administering the pharmaceutical composition as claimed in claim 1 to a subject in need thereof.
7 . The method as claimed in claim 6 , wherein the chronic pain is pain which extends over a period of 3-6 months or more, but before or after the period of time, one of the following characteristic signs is present, and a vegetative nervous dysfunction signs occur, lassitude, sleep disorders, decreased appetite, loss of taste, weight loss, hyposexuality, and constipation.
8 . The pharmaceutical composition as claimed in claim 1 , wherein the particle size of the active pharmaceutical ingredient is less than or equal to 30 mesh.
9 . The pharmaceutical composition as claimed in claim 1 , wherein the gastro-retentive tablet has a dosage ranging from 100 mg to 400 mg.
10 . The method as claimed in claim 6 , wherein the acute or chronic pain is non-neuropathic inflammatory pain.
11 . The method as claimed in claim 6 , wherein the acute or chronic pain is chronic inflammatory pain.
12 . The method as claimed in claim 7 , wherein the acute or chronic pain is rheumatoid arthritis pain or secondary osteoarthritis pain.