MXPA01002650A - Pharmaceutical composition comprising entacapone or nitecapone as well as a cross-linked cellulose derivative - Google Patents
Pharmaceutical composition comprising entacapone or nitecapone as well as a cross-linked cellulose derivativeInfo
- Publication number
- MXPA01002650A MXPA01002650A MXPA/A/2001/002650A MXPA01002650A MXPA01002650A MX PA01002650 A MXPA01002650 A MX PA01002650A MX PA01002650 A MXPA01002650 A MX PA01002650A MX PA01002650 A MXPA01002650 A MX PA01002650A
- Authority
- MX
- Mexico
- Prior art keywords
- cross
- cellulose derivative
- entacapone
- composition
- linked cellulose
- Prior art date
Links
- JRURYQJSLYLRLN-BJMVGYQFSA-N Entacapone Chemical compound CCN(CC)C(=O)C(\C#N)=C\C1=CC(O)=C(O)C([N+]([O-])=O)=C1 JRURYQJSLYLRLN-BJMVGYQFSA-N 0.000 title claims abstract description 49
- 229920002678 cellulose Polymers 0.000 title claims abstract description 49
- 239000001913 cellulose Substances 0.000 title claims abstract description 49
- 229960003337 entacapone Drugs 0.000 title claims abstract description 48
- UPMRZALMHVUCIN-UHFFFAOYSA-N Nitecapone Chemical compound CC(=O)C(C(C)=O)=CC1=CC(O)=C(O)C([N+]([O-])=O)=C1 UPMRZALMHVUCIN-UHFFFAOYSA-N 0.000 title claims abstract description 34
- 229950008980 Nitecapone Drugs 0.000 title claims abstract description 33
- 239000008194 pharmaceutical composition Substances 0.000 title description 5
- 239000000203 mixture Substances 0.000 claims abstract description 81
- 150000003839 salts Chemical class 0.000 claims abstract description 32
- 239000011780 sodium chloride Substances 0.000 claims abstract description 32
- 235000010980 cellulose Nutrition 0.000 claims description 45
- 239000003795 chemical substances by application Substances 0.000 claims description 28
- 229920002785 Croscarmellose sodium Polymers 0.000 claims description 18
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 claims description 10
- 239000008187 granular material Substances 0.000 claims description 10
- 229960001681 Croscarmellose Sodium Drugs 0.000 claims description 9
- 239000000314 lubricant Substances 0.000 claims description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 2
- 239000003826 tablet Substances 0.000 description 15
- 238000004090 dissolution Methods 0.000 description 13
- 230000002708 enhancing Effects 0.000 description 10
- 238000009472 formulation Methods 0.000 description 5
- 239000007916 tablet composition Substances 0.000 description 5
- 239000003085 diluting agent Substances 0.000 description 4
- 239000007884 disintegrant Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- FBPFZTCFMRRESA-KAZBKCHUSA-N D-Mannitol Natural products OC[C@@H](O)[C@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KAZBKCHUSA-N 0.000 description 3
- 102000006378 EC 2.1.1.6 Human genes 0.000 description 3
- 108020002739 EC 2.1.1.6 Proteins 0.000 description 3
- FBPFZTCFMRRESA-KVTDHHQDSA-N Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 239000001767 crosslinked sodium carboxy methyl cellulose Substances 0.000 description 3
- 238000007922 dissolution test Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000000594 mannitol Substances 0.000 description 3
- 235000010355 mannitol Nutrition 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 229960005168 Croscarmellose Drugs 0.000 description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 229940032147 Starch Drugs 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000008108 microcrystalline cellulose Substances 0.000 description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 2
- 239000008109 sodium starch glycolate Substances 0.000 description 2
- 229920003109 sodium starch glycolate Polymers 0.000 description 2
- 229940079832 sodium starch glycolate Drugs 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- PUSNGFYSTWMJSK-GSZQVNRLSA-N (2R,3R,4S,5R,6R)-2,3,4-trimethoxy-6-(methoxymethyl)-5-[(2S,3R,4S,5R,6R)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxyoxane;1-[[(2R,3R,4S,5R,6S)-3,4,5-tris(2-hydroxypropoxy)-6-[(2R,3R,4S,5R,6R)-4,5,6-tris(2-hydroxypropoxy)-2-(2-hydroxypropoxymethyl)oxan- Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](OC)O[C@@H]1COC.CC(O)CO[C@@H]1[C@@H](OCC(C)O)[C@H](OCC(C)O)[C@@H](COCC(O)C)O[C@H]1O[C@H]1[C@H](OCC(C)O)[C@@H](OCC(C)O)[C@H](OCC(C)O)O[C@@H]1COCC(C)O PUSNGFYSTWMJSK-GSZQVNRLSA-N 0.000 description 1
- 150000005206 1,2-dihydroxybenzenes Chemical class 0.000 description 1
- YJISHJVIRFPGGN-UHFFFAOYSA-N 5-[5-[3,4-dihydroxy-6-(hydroxymethyl)-5-methoxyoxan-2-yl]oxy-6-[[3,4-dihydroxy-6-(hydroxymethyl)-5-methoxyoxan-2-yl]oxymethyl]-3,4-dihydroxyoxan-2-yl]oxy-6-(hydroxymethyl)-2-methyloxane-3,4-diol Chemical compound O1C(CO)C(OC)C(O)C(O)C1OCC1C(OC2C(C(O)C(OC)C(CO)O2)O)C(O)C(O)C(OC2C(OC(C)C(O)C2O)CO)O1 YJISHJVIRFPGGN-UHFFFAOYSA-N 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L Calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 229940063834 Carboxymethylcellulose Sodium Drugs 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N D-sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 239000004129 EU approved improving agent Substances 0.000 description 1
- GUBGYTABKSRVRQ-UUNJERMWSA-N Lactose Natural products O([C@@H]1[C@H](O)[C@H](O)[C@H](O)O[C@@H]1CO)[C@H]1[C@@H](O)[C@@H](O)[C@H](O)[C@H](CO)O1 GUBGYTABKSRVRQ-UUNJERMWSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 229920000881 Modified starch Polymers 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinylpyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- 206010061536 Parkinson's disease Diseases 0.000 description 1
- 229940069328 Povidone Drugs 0.000 description 1
- CZMRCDWAGMRECN-GDQSFJPYSA-N Sucrose Natural products O([C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](CO)O1)[C@@]1(CO)[C@H](O)[C@@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-GDQSFJPYSA-N 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 229940005928 entacapone 200 MG Drugs 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 239000008172 hydrogenated vegetable oil Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 229960001855 mannitol Drugs 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000006011 modification reaction Methods 0.000 description 1
- 239000008203 oral pharmaceutical composition Substances 0.000 description 1
- 239000007935 oral tablet Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000000546 pharmaceutic aid Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 238000002798 spectrophotometry method Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
Abstract
The present invention relates to an oral compacted composition comprising entacapone, nitecapone, or a pharmaceutically acceptable salt thereof and a cross-linked cellulose derivative. The composition is premised on the discovery that the cross-linked cellulose derivative increases the release rate of entacapone or nitecapone from an oral compacted composition. Preferably the amount of the cross-linked cellulose derivative in the composition is at least 6%by weight, preferably from about 8%to about 16%weight, especially from about 10%to about 14%by weight.
Description
PHARMACEUTICAL COMPOSITION COMPRISING ENTACAPONE OR NITECAPONE AND A RETICULATED CELLULOSE DERIVATIVE
Field of the Invention The present invention relates to a novel pharmaceutical composition comprising a catechol derivative and a cross-linked cellulose derivative as a dissolution enhancing agent. Accordingly, the present invention relates to a compacted oral composition comprising entacapone, nitecapone or a pharmaceutically acceptable salt thereof and a cross-linked cellulose derivative as a dissolution enhancing agent. Particularly, the present invention relates to a compacted oral composition comprising entacapone, nitecapone or a pharmaceutically acceptable salt thereof and a cross-linked cellulose derivative, wherein the amount of the cross-linked cellulose derivative in the composition is at least 6. % by weight, more preferably about 8% to about 16% by weight, and especially about 10% to 14% by weight. Preferably the cross-linked cellulose derivative is cross-linked carboxymethylcellulose or a pharmaceutically acceptable salt thereof, and particularly croscarmellose sodium (for example cross-linked carboxymethylcellulose sodium, Ac-Di-Sol).
Preferably the compacted oral composition is in the form of a tablet. In addition, the present invention relates to a method of preparing a compacted oral composition comprising entacapone, nitecapone, or the pharmaceutically acceptable salt thereof and a cross-linked cellulose derivative. The present invention also relates to the use of a cross-linked cellulose derivative in the manufacture of a compacted oral composition comprising entacapone, nitecapone or a pharmaceutically acceptable salt thereof.
BACKGROUND OF THE INVENTION The chemical names of entacapone and nitecapone are (E) -2-cyano-3 - (3,4-dihydroxy-5-nitrophenyl) -N, N-diethyl-2-propenamide and 3 - (3, 4-dihydroxy-5-nitrobenzylidene) -2,4-pentanedione, respectively. Entacapone and nitecapone are described in US Patent No. 5,446,194 as inhibitors of catechol-O-methyltransferase (COMT). Enteral and parenteral administration routes are described in U.S. Patent No. 5,446,194. It is desirable that the entacapone, nitecapone and pharmaceutically acceptable salt thereof be released from the oral composition as soon as possible after ingestion. This can normally be achieved by using a dissolution enhancing agent in the pharmaceutical composition. The dissolving enhancing agent can be a disintegrant or any other agent that increases dissolution. There is a rough selection of different dissolution enhancing agents, including disintegrants, which are on the market, which have different chemical and physical characteristics. When the best solution enhancing agent for use in a pharmaceutical composition in combination with an active agent is selected, numerous factors have to be taken into consideration, for example, the chemical and physical characteristics of the active agent and the dissolution enhancing agent, chemical and physical characteristics of auxiliary agents, such as diluents and binders, the method of preparation of the composition, etc. A cross-linked cellulose derivative means an unmodified or modified cellulose polymer which is crosslinked in a manner generally known in the field of polymer chemistry. Said cross-linked cellulose derivatives are well known as excipients in the field of pharmaceutical technology and as an example may be mentioned the cross-linked carboxymethylcellulose or the pharmaceutically acceptable salt thereof. For example, croscarmellose sodium is a cross-linked sodium carboxymethyl cellulose polymer. According to the pharmaceutical excipients manual (Ainley Wade and Paul J. Weller, Second Edition, The Pharmaceutical Press, London, 1994), is used in oral pharmaceutical formulations as a disintegrator for tablets, capsules and granules. Concentrations of 0.5 to 5% w / w are generally used as disintegrators of the tablets. Neither the aforementioned patent nor any other patent or publication of which the applicants are informed disclose a compacted oral composition comprising entacapone, nitecapone or a pharmaceutically acceptable salt thereof, and a cross-linked cellulose derivative.
Summary of the Invention Applicants have discovered that a cross-linked cellulose derivative is a superior disintegrant for use in a compacted oral composition comprising entacapone, nitecapone or the pharmaceutically acceptable salt thereof. Accordingly, it is an object of the present invention to provide a compacted oral composition comprising entacapone, nitecapone or a pharmaceutically acceptable salt thereof and a cross-linked cellulose derivative. The composition is based on the discovery that the cross-linked cellulose derivative essentially increases the release range of entacapone or nitecapone from the compacted oral composition. Particularly, it is an object of the present invention to provide a compacted oral composition comprising entacapone, nitecapone or a pharmaceutically acceptable salt thereof and a cross-linked cellulose derivative, wherein the amount of the cross-linked cellulose derivative in the composition is thus less 6% by weight, more preferably approximately 8% to approximately 16% by weight, especially approximately 10% to 14% by weight. Preferably the cross-linked cellulose derivative is cross-linked carboxymethylcellulose or a pharmaceutically acceptable salt thereof, more preferably croscarmellose sodium (Ac-Di-Sol). Preferably, the compacted oral composition is in the form of a tablet and, therefore, an object of the present invention is to provide a tablet comprising entacapone, nitecapone or a pharmaceutically acceptable salt thereof and a cross-linked cellulose derivative. It is a further object of the present invention to provide a tablet comprising entacapone, nitecapone, or a pharmaceutically acceptable salt thereof and a cross-linked cellulose derivative, wherein the amount of the cross-linked cellulose derivative is at least 6% by weight. weight, more preferably about 8% to about 16% by weight, especially about 10% to about 14% by weight. An object of the present invention is also to provide a method for the preparation of a compacted oral composition comprising entacapone, nitecapone or a pharmaceutically acceptable salt thereof and a cross-linked cellulose derivative, wherein said method comprises mixing a pharmaceutically amount effective of entacapone, nitecapone or a pharmaceutically acceptable salt thereof, one or more auxiliary agents, and a cross-linked cellulose derivative to obtain a first mixture, - compact and grind the first mixture one or more times to obtain a plurality of granules; add a lubricant; a slider or a mixture thereof to the granules to obtain a second mixture; and compressing the second mixture into a plurality of tablets. It is an object of the present invention to provide a method for inhibiting catechol-O-methyltransferase by administering to a patient in need thereof a compacted oral composition comprising entacapone, nitecapone or a pharmaceutically acceptable salt thereof. A further aspect of the present invention relates to the use of a cross-linked cellulose derivative in the manufacture of a compacted oral composition comprising entacapone, nitecapone or a pharmaceutically acceptable salt thereof. In the following description, the additional objects and advantages of the present invention will be set in part, and in part will be obvious from the description, or may be learned by practicing the present invention. The objects and advantages of the present invention will be realized and achieved by means of the elements and combinations particularly pointed out in the appended claims. It should be understood that both the foregoing general description and the following detailed description of the invention are examples and are presented by way of explanation only and are not restrictive of the present invention as claimed.
BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 shows the effect of different solution-increasing agents in the solution of 200 mg entacapone compacted tablet formulations. Figure 2 illustrates the effect of croscarmellose sodium on the solution of the 200 mg entacapone compacted tablet formulations.
Detailed Description of the Invention Applicants have surprisingly discovered that the cross-linked cellulose derivative is effective in increasing the disintegration range of a compacted oral composition comprising entacapone, nitecapone or a pharmaceutically acceptable salt thereof. A compacted oral composition is a composition wherein a mixture of an active agent, one or more auxiliary agents and a dissolving agent is first compacted, then ground into granules, and further the granules are compacted to form a tablet or enclosed in one capsule The best dissolution enhancing agent is one that releases the active agent from the composition as soon as possible. Applicants discovered, that when compacting the nitecapone, entacapone or a pharmaceutically acceptable salt thereof together with the dissolution enhancing agents to form a compacted oral composition, the cross-linked cellulose derivative is unexpectedly more efficient to release the entacapone, nitecapone or a pharmaceutically acceptable salt thereof of the compacted composition than other common dissolution-improving agents, such as starch, pre-gelatinized starch, microcrystalline cellulose, mannitol, sodium starch glycolate, or sodium lauryl sulfate. The dissolution test of Example 1 shows that 90.1% of the entacapone is dissolved from a tablet comprising croscarmellose sodium as a disintegrant in 5 minutes (see Figure 1). This result is superior when compared to 69.3%, 55.4%, 41.3% and 8.4% of the tablets containing sodium lauryl sulfate, sodium starch glycolate, previously gelatinized starch and mannitol, respectively. Additionally, it is possible that the cross-linked cellulose derivative compacts nitecapone, entacapone or a salt thereof to a formulation which is both small in size (which is highly desirable in the treatment of certain conditions, for example in the treatment of Parkinson's disease) as well as superior to release nitecapone, entacapone or salt thereof. The cross-linked cellulose derivative is in the oral composition compacted in an amount to increase the dissolution of the active agent. Applicants have surprisingly discovered that the best dissolution results of the compacted oral compositions of the present invention are achieved when the amount of the cross-linked cellulose derivative is considerably greater than that suggested in the art. Accordingly, it has been found that the amount of crosslinked cellulose derivative in the compacted oral composition is preferably at least 6% by weight. More preferably, the amount of the cross-linked cellulose derivative is about 8% to about 16% by weight, especially about 10% to 14% by weight. The amount of entacapone, nitecapone or pharmaceutically acceptable salt thereof in the compacted oral composition depends on numerous factors known to those skilled in the art, such as, the type of mammal, the condition to be treated, the duration of the desired use, etc. The compacted composition of the present invention may also contain one or more different pharmaceutical active agents. The amount of entacapone in the tablet according to the present invention can be from about 5 to 400 mg, preferably from about 100 to 200 mg, more preferably 200 mg, entacapone and nitecapone can be prepared, for example, in accordance with US Patent No. 5446.194. An oral composition compacted in accordance with the present invention can be prepared by mixing a pharmaceutically effective amount of entacapone, nitecapone or a pharmaceutically acceptable salt thereof, one or more auxiliary agents derived from cross-linked cellulose, subsequently compacting and grinding the mixture to form granules. The compacted and ground can be done one or more times. The granules are then mixed with a lubricant, a slider or a mixture thereof and the mixture is compressed to form tablets. The tablets can be coated after processing. The granules can also be encapsulated to form capsules. The auxiliary agent can be a diluent, a linker or a mixture of different diluents and / or linkers. Preferably at least one of the auxiliary agents is soluble in water. Suitable diluents and linkers include, for example, microcrystalline cellulose, ipromellose (HPMC), povidone, starch, lactose, sucrose, mannitol, sorbitol, etc. Suitable lubricants and glidants include, for example, magnesium stearate, calcium stearate, hydrogenated vegetable oil, talc, silicon colloidal dioxide, etc. Those skilled in the art will recognize that other suitable auxiliary agents, lubricants and glidants may be used in the composition of the present invention.
The present invention will be further elucidated by means of the following examples, which are intended to be merely exemplary embodiments of the invention.
EXAMPLE 1 The dissolution of 200 mg entacapone tablet formulations containing different disintegrators was tested. The tablets were prepared by mixing, compacting, grinding and compressing the ingredients as described above. The formulations are those described in Table 1. The dissolution of each of the formulations was tested using a basket method with a speed of 100 rpm and a medium of 900 ml of phosphate buffer of pH 5.8. The amount of entacapone released was determined by the spectrophotometric method using a UV / VIS spectrophotometer. The detection wavelength was 313 nm. The results, which are presented in Figure 1, show that the croscarmellose sodium-containing formulation (Formula 5) releases entacapone faster.
TABLE 1 200 mg entacapone tablet formulations containing different dissolution enhancing agents, used in the dissolution test.
EXAMPLE 2 The effect of sodium of croscarmellose in the solution of the compacted tablet formulations of entacapone of 200 was tested according to the method described in Example 1. The different formulations, for example formulation 6 to formulation 10, are described in Table 2. The results of the dissolution test are illustrated in Figure 2. The formulation containing the most sodium of croscarmellose (100 mg) released entacapone more rapidly.
TABLE 2 Formulations of compacted entacapone tablets of 200 mg containing different amounts of croscarmellose sodium.
EXAMPLE 3 The compact oral compositions according to the present invention comprising entacapone as an active ingredient may include for example those ingredients which are described in Table No. 3.
TABLE 3 Different formulations of compacted oral tablets of entacapone 200 mg
Those skilled in the art will recognize that although specific embodiments have been illustrated and described, various modifications and changes may be made to them without departing from the spirit and scope of the present invention. Those skilled in the art will appreciate that there are other embodiments of the present invention, after considering the specification and practice of the present invention described herein. It is intended that the specification and examples be considered only as exemplary, the scope and true spirit of the present invention being indicated by the following claims. The references presented here are specifically incorporated as a reference in their entirety.
Claims (17)
1. - A compacted oral composition comprising a pharmaceutically effective amount of entacapone, nitecapone or a pharmaceutically acceptable salt thereof and a cross-linked cellulose derivative.
2. The composition according to claim 1, which comprises entacapone or a pharmaceutically acceptable salt thereof and a cross-linked cellulose derivative.
3. - The composition according to claim 1, characterized in that the amount of the cross-linked cellulose derivative in the composition is at least 6% by weight.
4. - The composition according to claim 3, characterized in that the amount of cross-linked cellulose derivative in the composition is about 8% 1 about 16% by weight.
5. - The composition according to claim 4, characterized in that the amount of crosslinked cellulose derivative of the composition is from about 10% to about 14% by weight.
6. The composition according to any of claims 1 to 5, characterized in that the cross-linked cellulose derivative is cross-linked carboxymethylcellulose or a pharmaceutically acceptable salt thereof.
7. The composition according to any of claims 1 to 6, wherein crosslinked cellulose derivative is croscarmellose sodium.
8. - The composition according to claim 1, wherein the composition is in the form of a tablet.
9. - The composition according to claim 2, wherein the amount of entacapone is from about 5 mg to about 400 mg.
10. - A method for preparing a compacted oral composition comprising entacapone, nitecapone or a pharmaceutically acceptable salt thereof, wherein said method comprises: a) mixing a pharmaceutically effective amount of entacapone, nitecapone or a pharmaceutically acceptable salt thereof, one or more auxiliary agents and a cross-linked cellulose derivative to obtain a first mixture; b) compacting and grinding the first mixture one or more times to obtain a plurality of granules; c) adding a lubricant, a slider, or a mixture thereof to the granules to obtain a second mixture; and d) compressing the second mixture to form a plurality of tablets.
11. - The method according to claim 10, wherein the amount of cross-linked cellulose derivative in the composition is at least 6% by weight.
12. - The method according to claim 11, wherein the amount of cross-linked cellulose derivative in the composition is from about 8% to about 16% by weight.
13. - The method according to claim 12, wherein the amount of crosslinked cellulose derivative in the composition is from about 10% to about 14% by weight.
14. - The method according to claim 10, wherein at least one of the auxiliary agents is soluble in water.
15. - The method according to claim 13, wherein the amount of entacapone is about 5 to about 400 mg.
16. The method according to any of claims 10 to 15, wherein the cross-linked cellulose derivative is cross-linked carboxymethylcellulose or a pharmaceutically acceptable salt thereof.
17. The method according to any one of claims JO to 16, wherein the cross-linked cellulose derivative is croscarmellose sodium.
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US09152263 | 1998-09-14 |
Publications (1)
Publication Number | Publication Date |
---|---|
MXPA01002650A true MXPA01002650A (en) | 2002-05-09 |
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