WO2006092732A2 - Stable solid dosage form of antihypertensive agent - Google Patents
Stable solid dosage form of antihypertensive agent Download PDFInfo
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- WO2006092732A2 WO2006092732A2 PCT/IB2006/000535 IB2006000535W WO2006092732A2 WO 2006092732 A2 WO2006092732 A2 WO 2006092732A2 IB 2006000535 W IB2006000535 W IB 2006000535W WO 2006092732 A2 WO2006092732 A2 WO 2006092732A2
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- solid dosage
- dosage form
- benazepril
- cellulose
- sodium
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- 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
- A61K9/2009—Inorganic compounds
-
- 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
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
-
- 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
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
- A61K9/2866—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
Definitions
- the present invention relates to stable pharmaceutical compositions of antihypertensive agent. More particularly, the present invention relates to stable solid dosage forms of benazepril hydrochloride.
- the present invention also relates to a process for the preparation of stable solid dosage forms of benazepril hydrochloride.
- Benazepril is 3 -[[1 -(ethoxycarbonyl)-3 -phenyl-( 1 S)-propyl] amino] -2,3 ,4,5 - tetrahydro-2-oxo- IH-I -(3 S)-benzazepine-l -acetic acid. It is marketed as monohydrochloride under the trade names LOTENSIN® in US and CIBACEN® in Europe. Benazepril hydrochloride is disclosed in U.S. Pat. No. 4,410,520, as an angiotensin converting enzyme inhibitor used as antihypertensive agent.
- Benazeprilat is the diacid form of benazepril formed by cleavage of the ester group, and is the active metabolite of benazepril. Benazepril and Benazeprilat may be administered in free or pharmaceutically acceptable salt form.
- LOTENSIN® is supplied as tablet containing 5mg, 10mg, 20mg & 40mg of benazepril hydrochloride for oral administration in the United States.
- LOTENSIN® comprise, in addition to benazepril hydrochloride as active ingredient, various inactive ingredients, which include a lubricant to avoid sticking & picking of powder blend to the punches in the tabletting process.
- the lubricant used in the 5 mg and 10 mg tablets is hydr ⁇ genated castor oil, while that used in the 40 mg tablets is magnesium stearate. ⁇ ydroge ⁇ ated castor oil is having additional application of lubricating die walls.
- Magnesium stearate is the most commonly used lubricant in pharmaceutical tablets.. However, it accelerates the rate of degradation of benazepril hydrochloride. Hence, the tablets of benazepril hydrochloride, which contain magnesium stearate, have a shorter shelf life than would be the case without magnesium stearate. It appears that 40 mg tablets could not be made using hydrogenated castor oil as the . only lubricant (i.e. without magnesium stearate) because hydrogenated castor oil is relatively ineffective as a lubricant, and is not sufficiently effective to eliminate sticking in the higher strength (40 mg) tablets.
- JP 2002-322064 describes a process for preparing stable benazepril tablets by using additives not containing an alkali metal and an alkaline earth metal.
- the main objective of present invention is to provide solid dosage forms of benazepril or its pharmaceutically acceptable salts, using lubricants, which are compatible with benazepril, and stable during storage. .
- Yet another objective of the present invention is to provide simple, cost effective and efficient process for preparing stable solid dosage forms of benazepril or its pharmaceutically acceptable salts.
- stable solid dosage form comprising benazepril or its pharmaceutically acceptable salts and a lubricant selected from the group consisting of sodium stearyl fumarate, talc, colloidal silicon dioxide, glyceryl dibehenate and the like or mixtures thereof.
- the stable solid dosage forms of benazepril further comprise pharmaceutically acceptable excipients such as diluents, di ' sintegrants, binders, glidants and the like.
- the stable solid dosage form of benazepril further comprises diuretics.
- diuretics include furosemide, spironolactone, chlorthalidone, amiloride, triamterene, and thiazide diuretics such as hydrochlorothiazide, chlorothiazide, flumethiazide, and bendroflumethiazide.
- the strength of benazepril used is 5 mg to 40 mg per dosage form.
- pharmaceutically acceptable salts as used herein includes inorganic or organic acids such as hydrochloride, hydrobromide, sulphate, nitrate, phosphate, formate, mesylate, citrate, benzoate, fumarate, maleate, tartrate and succinate.
- Sodium stearyl fumarate is an inert, hydrophilic tablet lubricant having good anti-adherent property, and shows less retardant effect on dissolution rate than magnesium stearate.
- the tablets made with sodium stearyl fumarate exhibit less sensitivity to blending time and have superior hardness characteristics compared to tablets produced with magnesium stearate even at higher concentration.
- Suitable glidants used in. accordance with the present invention are selected from talc, cornstarch, and colloidal silicon dioxide.
- Suitable diluents used in accordance with the present invention are selected from calcium phosphate-dibasic, calcium carbonate, lactose, sucrose, cellulose- microcrystalline, cellulose powdered, calcium silicate, kaolin, starch, starch pregelatinized, polyols such as mannitol, sorbitol, lactitol, xylitol, maltitol, sucrose or combinations thereof.
- Suitable disintegrants used in accordance with the present invention are selected from croscarmellose sodium, crospovidone, sodium starch glycolate, sodium carboxymethylcellulose, hydroxypropylcellulose, xanthan gum, alginic acid, alginates, carbopols and the like or combination thereof.
- Suitable binders according to the present invention are selected from methyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, polyvinylpyrrolidone, gelatin, gum arabic, ethyl cellulose, polyvinyl alcohol, starch, pregelatinized starch, agar, tragacanth, sodium alginate, propylene glycol, alginate, plasdone and the like.
- the lubricant used is in the range from about 0.2 to 3.0 % by weight of the composition.
- the solid dosage form of the present invention include tablets and capsules.
- the different formulation processes that can be employed for making the disclosed formulations are dry granulation (slugging, compaction), wet granulation, and direct compression.
- Benazepril tablets prepared by any of the above methods may optionally be coated with film forming materials such as hydroxypropyl methylcellulose, hydroxypropyl cellulose, and the like.
- wet granulation process' for the preparation of stable solid dosage form comprising benazepril or its pharmaceutically acceptable salts and a lubricant selected from- the group consisting of sodium stearyl fumarate, talc, colloidal silicon dioxide, glyceryl dibehenate and the like or mixtures thereof, comprising the steps of: i) blending benazepril with one or more diluents, disintegrants, binders, ii) granulating the blend obtained in step (i) with a solvent, iii) mixing the granules of step (ii) with one or more diluents, and disintegrants, iv) lubricating the blend of step . (iii), and v) compressing the blended granules to obtain tablet.
- the solvent used for preparing granules can be an aqueous and/or non-aqueous solvent.
- the non- aqueous solvent selected from alcohol or isopropyl alcohol.
- step (ii) mixed the materials of step (i) in a rapid mixer granulator
- step (iii) granulated the blend of step (ii) with purified water
- step (v) blended the dried granules of step (iv) with extragranular crospovidone in octagonal blender, . .
- step (ii) mixed the materials of step (i) in a rapid mixer granulator
- step (iii) granulated the blend of step (ii) with purified water
- step (v) blended the dried granules of step (iv) with extragranular crospovidone and colloidal silicon dioxide in octagonal blender,
- step (ii) mixed the materials of step (i) in a rapid mixer granulator
- step (iii) granulated the blend of step (ii) with purified water
- step (v) blended the dried granules of step (iv) with extragranular colloidal silicon dioxide, talc, and crospovidone in octagonal blender,
- step (ii) mixed the materials of step (i) in a rapid mixer granulator
- step (iii) granulated the blend of step (ii) with purified water
- step (v) blended the dried granules of step (iv) with extragranular colloidal silicon dioxide, talc, and crospovidone in octagonal blender,
- step (vi) compressed the blend of step (v) to obtain tablets, and coated the core tablets with film forming materials.
- step (ii) mixed the materials of step (i) in a rapid mixer granulator
- step (iii) granulated the blend of step (ii) with purified water
- step (v) blended the dried granules of step (iv) with extragranular colloidal silicon dioxide, and crospovidone in octagonal blender,
- Tablets of examples 8 and 9 as well as tablets with LOTENSIN® tablets (5 mg) were stored at 80 0 C for 2 days and then tested by an HPLC method to determine the degradation products as a percentage of the initial benazepril hydrochloride content. The results are shown in table 1.
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Abstract
The present invention relates to stable pharmaceutical compositions of antihypertensive agent. More particularly, the present invention relates to stable solid dosage forms of benazepril hydrochloride. The invention also relates to a process for the preparation of stable solid dosage forms of benazepril hydrochloride.
Description
STABLE SOLID DOSAGE FORM OF ANTIHYPERTENSIVE AGENT
Field of the invention
The present invention relates to stable pharmaceutical compositions of antihypertensive agent. More particularly, the present invention relates to stable solid dosage forms of benazepril hydrochloride.
The present invention also relates to a process for the preparation of stable solid dosage forms of benazepril hydrochloride.
Background of the invention
Benazepril is 3 -[[1 -(ethoxycarbonyl)-3 -phenyl-( 1 S)-propyl] amino] -2,3 ,4,5 - tetrahydro-2-oxo- IH-I -(3 S)-benzazepine-l -acetic acid. It is marketed as monohydrochloride under the trade names LOTENSIN® in US and CIBACEN® in Europe. Benazepril hydrochloride is disclosed in U.S. Pat. No. 4,410,520, as an angiotensin converting enzyme inhibitor used as antihypertensive agent. Benazeprilat is the diacid form of benazepril formed by cleavage of the ester group, and is the active metabolite of benazepril. Benazepril and Benazeprilat may be administered in free or pharmaceutically acceptable salt form.
LOTENSIN®, is supplied as tablet containing 5mg, 10mg, 20mg & 40mg of benazepril hydrochloride for oral administration in the United States. LOTENSIN® comprise, in addition to benazepril hydrochloride as active ingredient, various inactive ingredients, which include a lubricant to avoid sticking & picking of powder blend to the punches in the tabletting process. According to the literature for LOTENSIN™, the lubricant used in the 5 mg and 10 mg tablets is hydrόgenated castor oil, while that used in the 40 mg tablets is magnesium stearate. Ηydrogeήated castor oil is having additional application of lubricating die walls. Magnesium stearate is the most commonly used lubricant in pharmaceutical tablets.. However, it accelerates the rate of degradation of benazepril hydrochloride. Hence, the tablets of benazepril hydrochloride, which contain magnesium stearate, have a shorter shelf life
than would be the case without magnesium stearate. It appears that 40 mg tablets could not be made using hydrogenated castor oil as the . only lubricant (i.e. without magnesium stearate) because hydrogenated castor oil is relatively ineffective as a lubricant, and is not sufficiently effective to eliminate sticking in the higher strength (40 mg) tablets.
US 6,737,419 describes tablets of benazepril hydrochloride prepared by employing zinc stearate as the lubricant.
JP 2002-322064 describes a process for preparing stable benazepril tablets by using additives not containing an alkali metal and an alkaline earth metal.
It appears from the literature that there is possibility for the degradation of benazepril hydrochloride in a tablet containing magnesium stearate as lubricant. In order to avoid the possible degradation of benazepril with lubricants, inventors of the present invention found sodium stearyl fumarate, talc, colloidal silicon dioxide or their combination as lubricants for preparing stable tablets of benazepril. In addition, the inventors of the present invention found that shelf life and stability of solid dosage forms of the benazepril hydrochloride is increased when sodium steaiyl fumarate alone or in combination with talc or colloidal silicon dioxide is used as lubricant.
Objective of the invention
Accordingly, the main objective of present invention is to provide solid dosage forms of benazepril or its pharmaceutically acceptable salts, using lubricants, which are compatible with benazepril, and stable during storage. .
Yet another objective of the present invention is to provide simple, cost effective and efficient process for preparing stable solid dosage forms of benazepril or its pharmaceutically acceptable salts. • ■
Summary of the invention
According to the main embodiment of the present invention, there is provided stable solid dosage form comprising benazepril or its pharmaceutically acceptable salts and a lubricant selected from the group consisting of sodium stearyl fumarate, talc, colloidal silicon dioxide, glyceryl dibehenate and the like or mixtures thereof.
Detailed description of the invention
In an embodiment of the present invention, the stable solid dosage forms of benazepril further comprise pharmaceutically acceptable excipients such as diluents, di'sintegrants, binders, glidants and the like.
Ih yet another embodiment, the stable solid dosage form of benazepril further comprises diuretics. Suitable diuretics according to the present invention include furosemide, spironolactone, chlorthalidone, amiloride, triamterene, and thiazide diuretics such as hydrochlorothiazide, chlorothiazide, flumethiazide, and bendroflumethiazide.
In an embodiment of the present invention, the strength of benazepril used is 5 mg to 40 mg per dosage form.
The term pharmaceutically acceptable salts as used herein includes inorganic or organic acids such as hydrochloride, hydrobromide, sulphate, nitrate, phosphate, formate, mesylate, citrate, benzoate, fumarate, maleate, tartrate and succinate.
Sodium stearyl fumarate is an inert, hydrophilic tablet lubricant having good anti-adherent property, and shows less retardant effect on dissolution rate than magnesium stearate. The tablets made with sodium stearyl fumarate exhibit less sensitivity to blending time and have superior hardness characteristics compared to tablets produced with magnesium stearate even at higher concentration.
Suitable glidants used in. accordance with the present invention are selected from talc, cornstarch, and colloidal silicon dioxide.
Suitable diluents used in accordance with the present invention are selected from calcium phosphate-dibasic, calcium carbonate, lactose, sucrose, cellulose- microcrystalline, cellulose powdered, calcium silicate, kaolin, starch, starch pregelatinized, polyols such as mannitol, sorbitol, lactitol, xylitol, maltitol, sucrose or combinations thereof.
Suitable disintegrants used in accordance with the present invention are selected from croscarmellose sodium, crospovidone, sodium starch glycolate, sodium carboxymethylcellulose, hydroxypropylcellulose, xanthan gum, alginic acid, alginates, carbopols and the like or combination thereof.
Suitable binders according to the present invention are selected from methyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, polyvinylpyrrolidone, gelatin, gum arabic, ethyl cellulose, polyvinyl alcohol, starch, pregelatinized starch, agar, tragacanth, sodium alginate, propylene glycol, alginate, plasdone and the like.
In another embodiment of the present invention, the lubricant used is in the range from about 0.2 to 3.0 % by weight of the composition.
In an embodiment, the solid dosage form of the present invention include tablets and capsules.
The different formulation processes that can be employed for making the disclosed formulations are dry granulation (slugging, compaction), wet granulation, and direct compression.
Benazepril tablets prepared by any of the above methods may optionally be coated with film forming materials such as hydroxypropyl methylcellulose, hydroxypropyl cellulose, and the like.
In yet another embodiment of the present invention, there is provided wet granulation process' for the preparation of stable solid dosage form comprising benazepril or its pharmaceutically acceptable salts and a lubricant selected from- the
group consisting of sodium stearyl fumarate, talc, colloidal silicon dioxide, glyceryl dibehenate and the like or mixtures thereof, comprising the steps of: i) blending benazepril with one or more diluents, disintegrants, binders, ii) granulating the blend obtained in step (i) with a solvent, iii) mixing the granules of step (ii) with one or more diluents, and disintegrants, iv) lubricating the blend of step . (iii), and v) compressing the blended granules to obtain tablet.
The solvent used for preparing granules can be an aqueous and/or non-aqueous solvent. The non- aqueous solvent selected from alcohol or isopropyl alcohol.
The following examples further exemplify the inventions and are not intended to limit the scope of the inventions. It is obvious to those skilled in the art to find out the composition for other dosage forms and substitute the equivalent excipients' as described in this specification or with the one known to the industry.
The processing steps that were involved in making benazepril tablets described in example 1-4 are as given below:
(i) sifted benazepril hydrochloride, lactose, pregelatinized starch, microcrystalline cellulose, and crospovidone,
(ii) mixed the materials of step (i) in a rapid mixer granulator,
(iii) granulated the blend of step (ii) with purified water,
(iv) dried the granules of step (iii),
(v) blended the dried granules of step (iv) with extragranular crospovidone in octagonal blender, . .
(vi) lubricated the blend with sodium steaiyl fumarate,
(vii) compressed the lubricated blend to obtain tablets, and coated the core tablets with film forming materials.
Example 5
The processing steps that were involved in making benazepril tablets are as given below:
(i) sifted benazepril hydrochloride, lactose, pregelatinized starch, microcrystalline cellulose, and crospovidone,
(ii) mixed the materials of step (i) in a rapid mixer granulator,
(iii) granulated the blend of step (ii) with purified water,
(iv) dried the granules of step (iii),
(v) blended the dried granules of step (iv) with extragranular crospovidone and colloidal silicon dioxide in octagonal blender,
(vi) lubricated the blend with sodium stearyl fumarate,
(vii) compressed the lubricated blend to obtain tablets, and coated the core tablets with film forming materials.
Example 6
The processing steps that were involved in making benazepril tablets are as given below:
(i) sifted benazepril hydrochloride, lactose, pregelatinized starch, microcrystalline cellulose, and crospovidone,
(ii) mixed the materials of step (i) in a rapid mixer granulator,
(iii) granulated the blend of step (ii) with purified water,
(iv) dried the granules of step (iii),
(v) blended the dried granules of step (iv) with extragranular colloidal silicon dioxide, talc, and crospovidone in octagonal blender,
(vi) lubricated the blend with sodium stearyl fumarate,
(vii) compressed the lubricated blend to obtain tablets, and coated the core tablets with film forming materials. Example 7
Example 8
The processing steps that were involved in making benazepril tablets given in examples 7 & 8 are as given below:
(i) sifted benazepril hydrochloride, lactose, pregelatinized starch, microcrystalline cellulose, and crospovidone,
(ii) mixed the materials of step (i) in a rapid mixer granulator,
(iii) granulated the blend of step (ii) with purified water,
(iv) dried the granules of step (iii),
(v) blended the dried granules of step (iv) with extragranular colloidal silicon dioxide, talc, and crospovidone in octagonal blender,
(vi) compressed the blend of step (v) to obtain tablets, and coated the core tablets with film forming materials.
Example 9
The processing steps that were involved in making benazepril tablets are as given below:
(i) sifted benazepril hydrochloride, hydrochlorothiazide, lactose, pregelatinized starch, microcrystalline cellulose, and crospovidone,
(ii) mixed the materials of step (i) in a rapid mixer granulator,
(iii) granulated the blend of step (ii) with purified water,
(iv) dried the granules of step (iii),
(v) blended the dried granules of step (iv) with extragranular colloidal silicon dioxide, and crospovidone in octagonal blender,
(vi) lubricated the blend with sodium stearyl fumarate,
(vii) compressed the lubricated blend to obtain tablets, and coated the core tablets with film forming materials.
Example 10
Tablets of examples 8 and 9 as well as tablets with LOTENSIN® tablets (5 mg) were stored at 80 0C for 2 days and then tested by an HPLC method to determine the degradation products as a percentage of the initial benazepril hydrochloride content. The results are shown in table 1.
Table 1
It can be seen from the table 1, that the percentage of degradation is much lower for the tablets of examples 8 and 9 (which comprise sodium stearyl fumarate and talc / colloidal silicon dioxide as lubricant) than for either the tablets of example 10 (magnesium stearate as lubricant) or LOTENSIN® 5 mg tablets (hydrogenated vegetable oil as lubricant).
Claims
1. A stable solid dosage form comprising benazepril or its pharmaceutically acceptable salts and a lubricant selected from the group consisting of sodium stearyl fumarate, talc, colloidal silicon dioxide, glyceryl dibehenate or mixtures thereof.
2. The solid dosage form according to claim 1, further comprises diluents, disintegrants, binders, and glidants.
3. The solid dosage form according to claim 2, wherein the diluent is selected from calcium phosphate-dibasic, calcium carbonate, lactose, sucrose, cellulose- microcrystalline, cellulose powdered, calcium silicate, kaolin, starch, starch pregelatinized, polyols such as mannitol, sorbitol, lactitol, xylitol, maltitol, sucrose and combinations thereof.
4. The solid dosage form according to claim 2, wherein the disintegrant is selected from croscarmellose sodium, crospovidone, sodium starch glycolate, sodium carboxymethylcellulose, hydroxypropylcellulose, xanthan gum, alginic acid, alginates, carbopols or combinations thereof.
5. The solid dosage form according to claim 2, wherein the binder is selected from methyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, polyvinylpyrrolidone, gelatin, gum arabic, ethyl cellulose, polyvinyl alcohol, starch, pregelatinized starch, agar, tragacanth, sodium alginate, propylene glycol, alginate, or plasdone.
6. The solid dosage form according to claim 1, further comprise diuretic selected from furosemide, spironolactone, chlorthalidone, amiloride, triamterene, and thiazide diuretics such as hydrochlorothiazide, chlorothiazide, flumethiazide, and bendroflumethiazide.
7. A process for the preparation of form comprising benazepril or its pharmaceutically acceptable salts and a lubricant selected from the group consisting of sodium stearyl fumarate, talc, colloidal silicon dioxide, glyceryl dibehenate or mixtures thereof, comprising the steps of: i) blending benazepril with one or more diluents, disintegrants, binders, ii) granulating the blend obtained in step (i) with a solvent, iii) mixing the granules of step (ii) with one or more diluent, disintegrants, iv) . lubricating the blend of step (iii), and v) compressing the blended granules to obtain tablet.
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|---|---|---|---|
| IN208/CHE/2005 | 2005-03-04 | ||
| IN208CH2005 | 2005-03-04 |
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| WO2006092732A2 true WO2006092732A2 (en) | 2006-09-08 |
| WO2006092732A3 WO2006092732A3 (en) | 2007-03-29 |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008147601A1 (en) * | 2007-04-17 | 2008-12-04 | University Of Florida Research Foundation, Inc. | Methods and compositions for ameliorating thiazide induced hyperlipidemia |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002049646A1 (en) * | 2000-12-18 | 2002-06-27 | Novartis Ag | Therapeutic combination of amlodipine and benazepril/benazeprilat |
| US20020183308A1 (en) * | 2001-04-12 | 2002-12-05 | Sherman Bernard Charles | Benazepril Hydrochloride tablet formulations |
-
2006
- 2006-02-28 WO PCT/IB2006/000535 patent/WO2006092732A2/en not_active Application Discontinuation
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002049646A1 (en) * | 2000-12-18 | 2002-06-27 | Novartis Ag | Therapeutic combination of amlodipine and benazepril/benazeprilat |
| US20020183308A1 (en) * | 2001-04-12 | 2002-12-05 | Sherman Bernard Charles | Benazepril Hydrochloride tablet formulations |
Non-Patent Citations (3)
| Title |
|---|
| "Rote Liste 1996" 1996, ECV EDITIO CANTOR , FRANKFURT/MAIN , XP002411573 Description nr. 27 230 - Cibacen Filmtabletten * |
| "Rote Liste 1996" 1996, ECV EDITIO CANTOR , FRANKFURT/MAIN , XP002411574 Description nr. 17 105 - Cibadrex Filmtabletten * |
| LI SHOUFENG ET AL: "Correlation and prediction of moisture-mediated dissolution stability for benazepril hydrochloride tablets" PHARMACEUTICAL RESEARCH (DORDRECHT), vol. 21, no. 4, April 2004 (2004-04), pages 617-624, XP002411560 ISSN: 0724-8741 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008147601A1 (en) * | 2007-04-17 | 2008-12-04 | University Of Florida Research Foundation, Inc. | Methods and compositions for ameliorating thiazide induced hyperlipidemia |
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