CN111388431A - Oral preparation of lomitapide mesylate and preparation method thereof - Google Patents
Oral preparation of lomitapide mesylate and preparation method thereof Download PDFInfo
- Publication number
- CN111388431A CN111388431A CN202010136580.2A CN202010136580A CN111388431A CN 111388431 A CN111388431 A CN 111388431A CN 202010136580 A CN202010136580 A CN 202010136580A CN 111388431 A CN111388431 A CN 111388431A
- Authority
- CN
- China
- Prior art keywords
- mesylate
- microcrystalline cellulose
- preparation
- lomitapide mesylate
- lomitapide
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4468—Non condensed piperidines, e.g. piperocaine having a nitrogen directly attached in position 4, e.g. clebopride, fentanyl
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
Abstract
The invention relates to the technical field of medicines, in particular to an oral preparation of lometaside mesylate and a preparation method thereof, aiming at solving the problems of poor storage stability and reduced dissolution rate of the lometaside mesylate over time. The oral preparation of the lomitapide mesylate is a tablet, wherein the tablet is prepared from the components of the lomitapide mesylate, a filling agent, crospovidone, colloidal silicon dioxide (added internally), hydroxypropyl starch, colloidal silicon dioxide (added externally), talcum powder and the like in specific parts by weight. The oral preparation of the lomethapide mesylate successfully solves the problems of poor storage stability and reduced dissolution rate of the lomethapide mesylate over time, so that a new drug selection can be provided for patients.
Description
Technical Field
The invention relates to the technical field of medicines, and particularly relates to an oral preparation of lometasapine mesylate and a preparation method thereof.
Background
Hyperlipidemia, hyperlipidemia for short, also known as dyslipidemia, is a disease characterized by or associated with elevated lipid levels and/or lipoprotein levels in the blood, the types including hypercholesterolemia, hypertriglyceridemia, combined hyperlipidemia and elevated lipoprotein a (L p-a) and the like.
Hypercholesterolemia, particularly elevated low density lipoprotein cholesterol levels, is widely recognized as a major risk factor for developing significant cardiovascular disease such as atherosclerosis and coronary heart disease. Statins are first line therapeutics used to reduce low density lipoprotein cholesterol levels and thereby exert a prophylactic and/or therapeutic effect on hyperlipidemia, particularly hypercholesterolemia. However, there is still a high risk of cardiovascular disease in patients with about 1/4 clinically, and the extent of lipid lowering is not significant after receiving sufficient statin therapy. In addition, adverse reactions such as myalgia, rhabdomyolysis, etc. occur with statin administration, especially at higher doses of statin. Thus, there is a continuing need in the art for new therapies to reduce low density lipoprotein cholesterol levels.
Lomitapide mesylate (L omitapide mesylate) approved by the U.S. Food and Drug Administration (FDA) for marketing on 12/21 2012 was an oral microsomal triglyceride transfer protein inhibitor developed by Aegerion corporation for the treatment of hypercholesterolemia, including primary hypercholesterolemia and familial hypercholesterolemia.
Patent document WO2015121877 discloses a process for the preparation of amorphous powder of lometasdepa mesylate. However, the inventor finds that the problems of storage stability and dissolution rate can occur when the lometaside mesylate is prepared into a common oral tablet, and the content of the lometaside mesylate is reduced, impurities are increased and the dissolution rate is obviously reduced along with the storage time. Accordingly, there is an unmet need in the art to seek to solve the above problems of the oral tablet of lomitapide mesylate.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provide an oral preparation of lometasapine mesylate. The oral preparation of the lomethapide mesylate successfully solves the problems of poor storage stability and reduced dissolution rate of the lomethapide mesylate over time.
The invention also aims to provide a preparation method of the oral preparation of the lomitapide mesylate.
To this end, in one aspect of the present invention, there is provided an oral formulation of lomitapide mesylate characterized by: the oral preparation of the lomitapide mesylate is a tablet, wherein the tablet is prepared from the following components in parts by weight:
in one embodiment, the tablet is made from the following components in parts by weight:
in one embodiment, the filler is a composite filler consisting of microcrystalline cellulose PH 103, microcrystalline cellulose PH112, and glucosyl- β -cyclodextrin.
In one embodiment, the weight ratio of microcrystalline cellulose PH 103, microcrystalline cellulose PH112, and glucosyl- β -cyclodextrin is 1.5-6:1-4: 0.5-2.
In one embodiment, the weight ratio of microcrystalline cellulose PH 103, microcrystalline cellulose PH112, and glucosyl- β -cyclodextrin is 3:2: 1.
In another aspect, the present invention also provides a method for preparing an oral formulation of lomitapide mesylate according to the invention, the method comprising the steps of:
(1) uniformly mixing and crushing lomitapide mesylate, a filler, crospovidone and colloidal silicon dioxide (added internally) to obtain a premix;
(2) putting the premix obtained in the step (1) into a dry-method granulator to prepare a core material; and
(3) and (3) uniformly mixing the core material obtained in the step (2), hydroxypropyl starch, colloidal silicon dioxide (additionally added) and talcum powder, and then directly tabletting to obtain the oral preparation of the lomitapide mesylate.
In one embodiment, the pulverization in the step (1) is carried out by micronization using an air jet mill or a fluid energy mill.
In order that the spirit and substance of the present invention may be further understood, preferred embodiments of the present invention and effects thereof will now be described with reference to the following specific examples. It is to be understood that such description is merely illustrative of the features and advantages of the present invention, and is not intended to limit the scope of the claims.
Detailed Description
The present invention is not particularly limited in the source of all the raw materials used in the preparation of the oral formulation of lomitapide mesylate, and commercially available raw materials or raw materials prepared according to conventional methods well known to those skilled in the art may be used.
Example 1
The components and the amounts of the oral preparation of lometasapine mesylate described in this example are shown in the following table:
| components | Dosage (mg/tablet) |
| Lomitatapi mesylate | 40.00 |
| Microcrystalline cellulose PH 103 | 30.00 |
| Microcrystalline cellulose PH112 | 20.00 |
| Glucosyl- β -cyclodextrin | 10.00 |
| Cross-linked polyvidone | 8.00 |
| Colloidal silicon dioxide (inner adding) | 4.00 |
| Hydroxypropyl starch | 4.00 |
| Colloidal silicon dioxide (plus) | 1.00 |
| Talcum powder | 4.00 |
The preparation method comprises the following steps:
(1) uniformly mixing lomitapide mesylate, microcrystalline cellulose PH 103, microcrystalline cellulose PH112, glucosyl- β -cyclodextrin, crospovidone and colloidal silicon dioxide (internal addition), and micronizing by adopting a fluid energy mill to obtain a premix;
(2) putting the premix obtained in the step (1) into a dry-method granulator to prepare a core material; and
(3) and (3) uniformly mixing the core material obtained in the step (2), hydroxypropyl starch, colloidal silicon dioxide (additionally added) and talcum powder, and then directly tabletting to obtain the oral preparation of the lomitapide mesylate.
Comparative examples 1 to 4
The components and the amounts of the oral formulations of lomitapide mesylate described in comparative examples 1-4 are shown in the following table:
the preparation method comprises the following steps:
(1) uniformly mixing lomitapide mesylate, a filler (microcrystalline cellulose PH 103 or microcrystalline cellulose PH112 or glucosyl- β -cyclodextrin or lactose), crospovidone and colloidal silicon dioxide (added internally), and micronizing by a fluid energy mill to obtain a premix;
(2) putting the premix obtained in the step (1) into a dry-method granulator to prepare a core material; and
(3) and (3) uniformly mixing the core material obtained in the step (2), hydroxypropyl starch, colloidal silicon dioxide (additionally added) and talcum powder, and then directly tabletting to obtain the oral preparation of the lomitapide mesylate.
Experimental examples stability and dissolution Studies
Oral formulations of lometaside mesylate were prepared according to the methods of example 1 and comparative examples 1 to 4 of the present invention, respectively, by taking 60 tablets each, placing in the light (4500L ux), at a constant temperature (40 ℃) and at high humidity (RH 75%), then taking 12 tablets each at time points of 1 month, 3 months, 6 months, 1 year and 2 years, detecting the content of lometaside mesylate by high performance liquid chromatography and determining the dissolution of lometaside mesylate (15 minutes) by the rotating bar method.
The experimental results are as follows:
table 1: content change of lomitapide mesylate over time
Table 2: dissolution rate change of lometaside mesylate with time
The above results show that the oral formulation of lometaside mesylate prepared by the method of example 1 according to the present invention can significantly improve the problems of poor storage stability and reduced dissolution rate of lometaside mesylate over time, so that the oral formulation can maintain good drug stability and dissolution rate over a long period of time, thereby ensuring the effectiveness of administration.
The foregoing is only a preferred embodiment of the present invention. It should be noted that, for those skilled in the art, without departing from the spirit and principle of the present invention, several improvements, modifications, equivalents and the like can be made, and these improvements, modifications, equivalents and the like also should be regarded as falling within the protection scope of the present invention.
Claims (10)
1. An oral preparation of lomitapide mesylate, which is characterized in that: the oral preparation of the lomitapide mesylate is a tablet, wherein the tablet is prepared from the following components in parts by weight:
2. the oral formulation of lomitapide mesylate according to claim 1, wherein the tablet is prepared from the following components in parts by weight:
3. the oral formulation of lomitapide mesylate according to claim 1 or 2, wherein the filler is a composite filler consisting of microcrystalline cellulose PH 103, microcrystalline cellulose PH112, and glucosyl- β -cyclodextrin.
4. The oral formulation of lomitapide mesylate according to claim 3, wherein the weight ratio of the microcrystalline cellulose PH 103 to the microcrystalline cellulose PH112 to the glucosyl- β -cyclodextrin is 1.5-6:1-4: 0.5-2.
5. The oral formulation of lomitapide mesylate according to claim 4, wherein the weight ratio of the microcrystalline cellulose PH 103 to the microcrystalline cellulose PH112 to the glucosyl- β -cyclodextrin is 3:2: 1.
6. A process for the preparation of an oral formulation of lomitapide mesylate according to claim 1 or 2, comprising the steps of:
(1) uniformly mixing and crushing lomitapide mesylate, a filler, crospovidone and colloidal silicon dioxide (added internally) to obtain a premix;
(2) putting the premix obtained in the step (1) into a dry-method granulator to prepare a core material; and
(3) and (3) uniformly mixing the core material obtained in the step (2), hydroxypropyl starch, colloidal silicon dioxide (additionally added) and talcum powder, and then directly tabletting to obtain the oral preparation of the lomitapide mesylate.
7. The process of claim 6, wherein the milling in step (1) is achieved by micronization using a jet mill or a fluid energy mill.
8. The method according to claim 6 or 7, wherein the filler is a composite filler consisting of microcrystalline cellulose PH 103, microcrystalline cellulose PH112 and glucosyl- β -cyclodextrin.
9. The method according to claim 8, wherein the weight ratio of microcrystalline cellulose PH 103, microcrystalline cellulose PH112 and glucosyl- β -cyclodextrin is 1.5-6:1-4: 0.5-2.
10. The method of claim 9, wherein the weight ratio of microcrystalline cellulose PH 103, microcrystalline cellulose PH112, and glucosyl- β -cyclodextrin is 3:2: 1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010136580.2A CN111388431A (en) | 2020-03-02 | 2020-03-02 | Oral preparation of lomitapide mesylate and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010136580.2A CN111388431A (en) | 2020-03-02 | 2020-03-02 | Oral preparation of lomitapide mesylate and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN111388431A true CN111388431A (en) | 2020-07-10 |
Family
ID=71410817
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010136580.2A Withdrawn CN111388431A (en) | 2020-03-02 | 2020-03-02 | Oral preparation of lomitapide mesylate and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN111388431A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115869310A (en) * | 2021-09-27 | 2023-03-31 | 汕头大学医学院 | Targeted application of lomitapide in inhibiting FZD10 high-expression tumors |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103690960A (en) * | 2013-12-18 | 2014-04-02 | 北京科源创欣科技有限公司 | Lomitapide mesylate medicinal composition and preparation method thereof |
-
2020
- 2020-03-02 CN CN202010136580.2A patent/CN111388431A/en not_active Withdrawn
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103690960A (en) * | 2013-12-18 | 2014-04-02 | 北京科源创欣科技有限公司 | Lomitapide mesylate medicinal composition and preparation method thereof |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115869310A (en) * | 2021-09-27 | 2023-03-31 | 汕头大学医学院 | Targeted application of lomitapide in inhibiting FZD10 high-expression tumors |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103800279B (en) | atorvastatin calcium composition | |
| JP6019101B2 (en) | Formulation containing 2-amino-2- [2- (4-octylphenyl) ethyl] propane-1,3-diol | |
| CN101380290A (en) | Novel controlled release-niacin formulation | |
| JP2012025778A (en) | Fenofibrate-containing composition | |
| CN101972260B (en) | Rosuvastatin calcium oral drug composition | |
| CN107126423B (en) | Pitavastatin calcium tablet pharmaceutical composition and dry or wet preparation method thereof | |
| CN109674754B (en) | Flupentixol and melitracen pharmaceutical composition and preparation thereof | |
| CN109771386B (en) | Flupentixol melitracen tablet and preparation method thereof | |
| CN111388431A (en) | Oral preparation of lomitapide mesylate and preparation method thereof | |
| CN113230222B (en) | High-stability blood lipid-lowering pharmaceutical preparation and preparation method thereof | |
| CN108421045B (en) | Atorvastatin calcium composition, preparation and preparation method thereof | |
| CN101766594A (en) | Officinal composition for lowering blood fat | |
| CN114533691A (en) | Apremilast tablet and industrial preparation method thereof | |
| JP2006520770A (en) | Process for producing pharmaceutical composition in the form of tablets containing fibrates and tablets obtained according to said process | |
| CN112641750A (en) | Paroxetine hydrochloride tablet and preparation method thereof | |
| CN107811989B (en) | Rosuvastatin calcium pharmaceutical composition and preparation method thereof | |
| CN111450073A (en) | Pharmaceutical composition containing cinacalcet hydrochloride and preparation method thereof | |
| CN114099506B (en) | Pharmaceutical composition containing sorafenib | |
| JP2020015689A (en) | Levocetirizine-containing tablet | |
| CN114727965B (en) | JAK kinase inhibitor pharmaceutical composition | |
| WO2023093640A1 (en) | Darolutamide pharmaceutical composition, preparation method therefor and use thereof | |
| CN106539807B (en) | Stable pharmaceutical composition and preparation method thereof | |
| CN115887406A (en) | Preparation method of crizotinib capsule | |
| CN114588123A (en) | High-stability cetirizine hydrochloride tablet and preparation method thereof | |
| CN114983956A (en) | Mirabegron sustained release tablet and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| CB02 | Change of applicant information |
Address after: 157011 Mudanjiang Medical University, Aimin Road, Aimin District, Heilongjiang, Mudanjiang, 3 Applicant after: MUDANJIANG MEDICAL University Address before: 157011 the Second Affiliated Hospital of Mudanjiang Medical University, Heilongjiang, Mudanjiang Applicant before: MUDANJIANG MEDICAL University |
|
| CB02 | Change of applicant information | ||
| WW01 | Invention patent application withdrawn after publication |
Application publication date: 20200710 |
|
| WW01 | Invention patent application withdrawn after publication |