Method of bacampycillin acid salt microcapsulation

专利摘要:
A novel formulation of bacampicillin for oral administration is disclosed. Microcapsules comprising an acid addition salt of bacampicillin coated with a mixture of ethyl cellulose:water-soluble or water-permeable filler material are suspended in a buffered vehicle having a pH of at least 6.9. The novel suspension is characterized by palatable taste, surprisingly good stability and enhanced bioavailability after oral administration. The novel suspension is well suited for multiple dose oral administration. The preferred filler material is hydroxypropyl cellulose.
公开号:SU1364226A3
申请号:SU813310057
申请日:1981-07-09
公开日:1987-12-30
发明作者:Ли Битти Морган
申请人:Пфайзер Инк (США)；
IPC主号:

专利说明:

The invention relates to the pharmaceutical industry, and in particular to methods of microcapsules, an acid salt of Bacampicillin.
The purpose of the invention is to increase the durability of the target product,
The method is carried out as follows.
The acid salt of bacampicillin is mixed with ethyl cellulose, while oxypropane 1 is added (sesoT1 on the ratio of ethyl cellulose and oxypropyl cellulose 1.5: 1-2: 1 at pH 7.2-8.2 by weight to 25-100% by weight of the core ;
Example G. Preparation of bacampicillin hydrochloride microcapsules. Prepare a solution containing 48 g / l of ethyl cellulose, 32 g / l of hydroxypropyl cellulose and acetone in the amount to equilibrium the system. Then the solution is filtered through cheesecloth. Bacampicillin hydrate powder, sifted through a 50-mesh sieve (0.29 mm), in an amount of 940 g, is suspended in a Warster granulating chamber, carried out liquidization using humidified air with a temperature of 32 ° C and spraying the above filtered solution until a shell of 35% by weight of Bacum pitsillin hydrochloride mass on particles of ampicillin hydrochloride will not be obtained. This casing contains ethyl cellulose and hydroxypropyl cellulose in a ratio of 1.5: 1. The resulting microcapsules are passed through a 40 mesh sieve (0.42 mm). Then, the microcapsules (663 g) are dried under vacuum for 4 hours at which point, and then for another 16 hours in vacuum without heating.
Example 2: Preparation of a dry powder for preparing a formulation. These ingredients (g) are mixed for 30 minutes in a V-shaped mixer:
Sodium bicarbonate 31, 4
. Mannit334.3
Sodium carboxymethyl cellulose 31,4
Ksanuanov Resin62,7
Extruded sugar2194.0
Cushioning substance, sweet cherry smell 55.0 Sodium benzoag 31.4 The mixture is passed through a 40 mesh sieve (0.42 mm), again stirred for 15 minutes in a V-shaped
the mixer, then stirred for 10 minutes in a V-shaped mixer with 158.8. g microcapsules of bacampicillin hydrochloride prepared according to example 1. The strength of this dry powder is 85%, the biological activity is maintained for 6 weeks. at 50 ° C.
0 Example 3. The preparation of a suspension intended for insertion through the mouth.
The dry powder prepared according to Example 2 is mixed with water, the mixture 5 is thoroughly shaken — manually — as a result, an aqueous suspension is obtained, which is intended for oral administration, having a biological activity of 200 mg bacampiocillin hydrochloride per 10 ml of injected water This suspension has a pH of 7.6 and a resistance of 89%, its biological activity is maintained for 14 days at 5 ° C. Example 4. The above ingredients (g) are weighed and stirred for 30 minutes in a V-blender, after each of them are dried in a shelf drier for 16 hours at 50 ° C: sodium bicarbonate 77.5
0 Mannitol 837.5
Sodiumcarboxymethylcellulose25.0
Xanthan gum50,0
Titanium dioxide157,5
5 Extruded sugar5480,0
Saccharin sodium 25,0
The mixture is then passed through a Fitzpatirick mill to remove large pieces. The resulting material is mixed for 30 minutes in a V-shaped mixer with 199.0 g of cherry flavoring and 872.0 g of baccampicillin hydrochloride microcapsules — 5–35% by weight of an ethylcellulose and hydroxypropylcellulose envelope in bulk. 1.5: 1 ratio. Microcapsules were prepared as described in Example 1. The resulting mixture was dried for 2 hours at 50 ° C under vacuum. The strength of this dry powder, intended for the preparation of the formulation, is such that after 12 weeks. when biological activity is preserved at 97%. 55 Example 5. Preparation of a suspension to be administered through the mouth.
Similar to the example. 3 an aqueous suspension is prepared for entry into
using poTj using a dry powder for preparing a formulation prepared according to Example 4. This suspension has a biological activity of 200 mg of bacilli picampillin propylhydride per 5 ml of suspension pH 7.4 and retains 95% of its biological activity after 14 days. 3-3,5 ° C.
Example 6 Preparation of a dry powder for preparing a formulation.
Analogously to example 4, a mixture is obtained consisting of the following ingredients, g: Microcapsules of chlorhydrate and bacampicillin 35% by weight of a shell made of ethyl cellulose and hydroxypropyl
cellulose (mass ratio 1.5: 1) obtained in Example 1-3864.0 Sodium bicarbonate 739.3 Mannitol 3580.0 Sodium carboxymethylcellulose 107.0 Xanthan gum 214.0 Titanium dioxide 674.1 Pressed sugar 23460.0 Saccharin sodium 107.0 Damping substance imparting
cherry smell 882,4
Example 7: Preparation of a suspension to be administered through the mouth.
Analogously to example 3, an aqueous suspension is prepared, intended by T. Zhuravkina’s editor M. Petrov’s Editor Tehred L. Serdyukov Proofreader V. But gas order 6386/58 Circulation 595 Subscription
VNIIPI USSR State Committee
for inventions and discoveries 113035, Moscow, Zh-35, Raushsk nab., 4/5
Production and printing company, Uzhgorod, st. Project, 4
for oral administration from a dry powder for preparing a formulation prepared according to Example 6. This suspension has a biological activity of 125 mg of bacpamicillin hydrochloride per 5 ml of suspension and resistance, corresponding to 94% of the biological activity after 14 days at 3-5 ,.
A distinctive feature of this invention is that the prepared suspension has a high resistance, which allows it to be used as a multiple dose when administered through the mouth, even when the pH of the aqueous suspension medium is much higher than that which causes problems with the resistance of bacampicillin in an aqueous medium. - New suspension is distinguished by its pleasant taste with surprisingly good stability and increased biological utility after oral administration. The slurry is well suited for multiple internal use.

权利要求:
Claims (1)
[1]
Invention Formula
The microcapsule method of the acid salt of bacillus cillin by blending with ethyl cellulose is different from and. in order to increase the stability of the target product, hydroxypropylcellulose is added at the ratio of ethylcellulose and hydroxypropylcellulose 1, 5: J-2: 1 at a pH of 7.2-8.2 j to the coating weight of 25-100% of core mass.

类似技术:

---

公开号 | 公开日 | 专利标题

---

SU1364226A3|1987-12-30|Method of bacampycillin acid salt microcapsulation

---

CA1291044C|1991-10-22|Spray dried acetaminophen

---

US4835188A|1989-05-30|Spray dried ibuprofen

---

US4835187A|1989-05-30|Spray dried ibuprofen

---

JP4129995B2|2008-08-06|Pharmaceutical composition for rapid suspension in an aqueous medium

---

JP3667778B2|2005-07-06|Spheroid preparation

---

EP1027038B1|2006-07-05|Taste masked pharmaceutical compositions

---

EP1722821B1|2016-01-13|Composition for oral administration of tamsulosin hydrochloride and controlled release granule formulation comprising same

---

US20080275124A1|2008-11-06|Powder of amino acids and method for producing the same

---

IE61952B1|1994-11-30|Spray dried acetaminophen

---

IL173481A|2010-06-30|Polysaccharide double-layer microcapsules as carriers for biologically active substance for oral administration

---

EP0268383B1|1991-06-12|Spray dried acetaminophen

---

US5460829A|1995-10-24|Pharmaceutical compositions based on ebastine or analogues thereof

---

US4771077A|1988-09-13|Spray dried acetaminophen

---

HU229936B1|2015-01-28|Particles coated with granulated crystalline ibuprofen

---

US3922379A|1975-11-25|Microencapsulation process

---

US20040213839A1|2004-10-28|Methods and compositions for reducing the taste of pharmaceutically active agents

---

WO1998004243A1|1998-02-05|Preparation of colored powders/granulates by means of a fluid bed drying apparatus

---

JP3456211B2|2003-10-14|Long-acting formulation

---

JPH05168421A|1993-07-02|Stable preparation of colistin sulfate-containing feed

---

EP0557064B1|1997-06-11|Modified release formulation

---

US20210046010A1|2021-02-18|Tablets containing arginine at high concentration

---

JP2001278806A|2001-10-10|Colistin sulfate stabilized preparation

---

JPH09110706A|1997-04-28|Production of granule containing useful intestinal bacterium

---

EP1051969A1|2000-11-15|Coated antibiotic granules

同族专利:

---

公开号 | 公开日

---

CA1137414A|1982-12-14|

---

GB2082539A|1982-03-10|

---

NZ198106A|1983-12-16|

---

DZ315A1|2004-09-13|

---

FR2488798A1|1982-02-26|

---

CH650674A5|1985-08-15|

---

NO812827L|1982-02-23|

---

CS225845B2|1984-02-13|

---

MY8600597A|1986-12-31|

---

GB2082539B|1984-01-18|

---

NL191978C|1996-12-03|

---

GR74983B|1984-07-12|

---

ATA362781A|1982-10-15|

---

ZA815793B|1982-08-25|

---

ES504905A0|1983-02-01|

---

KR830005850A|1983-09-14|

---

AU7441681A|1982-04-01|

---

HK43786A|1986-06-20|

---

JPH0248525B2|1990-10-25|

---

IE51506B1|1987-01-07|

---

US4321253A|1982-03-23|

---

SE8104974L|1982-02-23|

---

NO154821C|1987-01-07|

---

IT1138161B|1986-09-17|

---

NO154821B|1986-09-22|

---

IN156538B|1985-08-31|

---

JPS5775986A|1982-05-12|

---

YU43985B|1990-02-28|

---

DK158971B|1990-08-13|

---

FR2488798B1|1985-01-11|

---

PL232141A1|1982-03-15|

---

DE3132614C2|1985-08-22|

---

PH17125A|1984-06-01|

---

NL8103902A|1982-03-16|

---

ES8303091A1|1983-02-01|

---

BE890028A|1982-02-22|

---

IL63617A|1984-11-30|

---

KE3626A|1986-05-16|

---

DK158971C|1991-01-07|

---

RO82679A|1984-05-23|

---

DK372181A|1982-02-23|

---

RO82679B|1984-07-30|

---

FI72647B|1987-03-31|

---

HU188679B|1986-05-28|

---

IE811911L|1982-02-22|

---

IL63617D0|1981-11-30|

---

DD201644A5|1983-08-03|

---

SE448819B|1987-03-23|

---

MX5731A|1993-11-01|

---

LU83572A1|1982-04-14|

---

KR860000513B1|1986-05-02|

---

DE3132614A1|1982-05-19|

---

FI812574L|1982-02-23|

---

NL191978B|1996-08-01|

---

PT73555B|1983-07-14|

---

AU529965B2|1983-06-30|

---

AT370994B|1983-05-25|

---

BG42000A3|1987-09-15|

---

YU201781A|1984-04-30|

---

AR227201A1|1982-09-30|

---

FI72647C|1987-07-10|

---

PT73555A|1981-09-01|

---

IT8123587D0|1981-08-20|

引用文献:

---

公开号 | 申请日 | 公开日 | 申请人 | 专利标题

---

---

US3549746A|1967-11-02|1970-12-22|Bristol Myers Co|Antibiotic composition|

---

US3873521A|1970-09-17|1975-03-25|Astra Laekemedel Ab|Esters of {60 -amino penicillins|

---

ZA718014B|1970-12-23|1972-08-30|Beecham Group Ltd|Pharmaceutical formulations|

---

US4016254A|1972-05-19|1977-04-05|Beecham Group Limited|Pharmaceutical formulations|

---

GB1455296A|1973-05-24|1976-11-10|Beecham Group Ltd|Veterinary treatment|

---

GB1479655A|1974-03-08|1977-07-13|Beecham Group Ltd|Antibiotic preparations|

---

US4127647A|1975-04-08|1978-11-28|Meiji Seika Kaisha, Ltd.|Process for preparation of stable amorphous macrolide antibiotic solids|

---

JPS5840529B2|1975-09-29|1983-09-06|Meiji Seika Co|

---

GB1561301A|1976-01-02|1980-02-20|Beecham Group Ltd|Orally administrable pharmaceutical composition|

---

ZA793934B|1978-08-04|1980-07-30|Beecham Group Ltd|Powders|

---

JPH0130617B2|1980-12-23|1989-06-21|Hitachi Cable|CH647676A5|1978-12-22|1985-02-15|Donald E Panoz|ORAL, PROGRAM RELEASED GALENIC FORMS AND METHODS OF PREPARING THE SAME.|

---

US4994260A|1982-05-28|1991-02-19|Astra Lakemedel Aktiebolag|Pharmaceutical mixture|

---

SE8103843L|1981-06-18|1982-12-19|Astra Laekemedel Ab|PHARMACEUTICAL MIXTURE|

---

WO1984000004A1|1982-06-14|1984-01-05|Key Pharma|Sustained release aspirin|

---

US4508702A|1982-06-14|1985-04-02|Key Pharmaceuticals, Inc.|Sustained release aspirin|

---

SE8203953D0|1982-06-24|1982-06-24|Astra Laekemedel Ab|PHARMACEUTICAL MIXTURE|

---

EP0113373B1|1982-07-09|1991-08-28|Key Pharmaceuticals, Inc.|Sustained release quinidine dosage form|

---

US4634587A|1982-07-09|1987-01-06|Key Pharmaceuticals, Inc.|Sustained release quinidine dosage form|

---

AU569277B2|1983-03-03|1988-01-28|Dow Chemical Company, The|Aqueuos dispersion of water-insoluble organophilic cellulose ether for sustained release of active agents|

---

US4555399A|1983-11-18|1985-11-26|Key Pharmaceuticals, Inc.|Aspirin tablet|

---

IE58110B1|1984-10-30|1993-07-14|Elan Corp Plc|Controlled release powder and process for its preparation|

---

SE8405611D0|1984-11-09|1984-11-09|Astra Laekemedel Ab|PROCESS FOR STABILIZATION OF BACAMPICILLIN HYDROCHLORIDE|

---

US4800087A|1986-11-24|1989-01-24|Mehta Atul M|Taste-masked pharmaceutical compositions|

---

GB8628359D0|1986-11-27|1986-12-31|Zyma Sa|Galenical formulation|

---

US4853229A|1987-10-26|1989-08-01|Alza Corporation|Method for adminstering tiny pills|

---

US5084278A|1989-06-02|1992-01-28|Nortec Development Associates, Inc.|Taste-masked pharmaceutical compositions|

---

SK279329B6|1992-04-30|1998-10-07|Schering Corporation|Stable hydrated cephalosporin dry powder, method of its preparation and formulation thereof|

---

US6270795B1|1995-11-09|2001-08-07|Microbiological Research Authority|Method of making microencapsulated DNA for vaccination and gene therapy|

---

US6270804B1|1998-04-03|2001-08-07|Biovail Technologies Ltd.|Sachet formulations|

---

IN191482B|1999-03-19|2003-12-06|Ranbaxy Lab Ltd|

---

JP4711478B2|1999-08-13|2011-06-29|旭化成ケミカルズ株式会社|Taste masked drug|

---

US20050037086A1|1999-11-19|2005-02-17|Zycos Inc., A Delaware Corporation|Continuous-flow method for preparing microparticles|

---

KR100558239B1|1999-12-23|2006-03-10|화이자 프로덕츠 인크.|Pharmaceutical Compositions Providing Enhanced Drug Concentrations|

---

EP1118333A1|2000-01-18|2001-07-25|Eurand International S.P.A.|Compositions with enhanced oral bioavailability|

---

AT361061T|2000-04-20|2007-05-15|Novartis Ag|COATING COMPOSITION FOR TASTE MASKING|

---

US6551617B1|2000-04-20|2003-04-22|Bristol-Myers Squibb Company|Taste masking coating composition|

---

WO2001093835A1|2000-06-02|2001-12-13|Zycos Inc.|Delivery systems for bioactive agents|

---

FR2822834B1|2001-04-02|2005-02-25|Flamel Tech Sa|COLLOIDAL SUSPENSION OF NANOPARTICLES BASED ON AMPHIPHILIC COPOLYMERS FOR VECTORIZATION OF ACTIVE INGREDIENTS AND THEIR METHOD OF PREPARATION|

---

JP2004532257A|2001-05-31|2004-10-21|シーマ・ラブス、インコーポレイテッド|Taste masking of highly water-soluble drugs|

---

KR20030015655A|2001-08-17|2003-02-25|한미약품공업 주식회사|Crystalline acid-added salt of an indane-based compound for increasing oral absorption of an anti-cancer agent, preparation thereof and pharmaceutical composition comprising same|

---

FR2830447B1|2001-10-09|2004-04-16|Flamel Tech Sa|MICROPARTICULAR ORAL GALENIC FORM FOR DELAYED AND CONTROLLED RELEASE OF PHARMACEUTICAL ACTIVE INGREDIENTS|

---

US8101209B2|2001-10-09|2012-01-24|Flamel Technologies|Microparticulate oral galenical form for the delayed and controlled release of pharmaceutical active principles|

---

DE60325709D1|2002-04-09|2009-02-26|Flamel Tech Sa|ORAL AQUEOUS SUSPENSION CONTAINING MICRO CAPSULES FOR THE CONTROLLED RELEASE OF ACTIVE SUBSTANCES|

---

IL164221D0|2002-04-09|2005-12-18|Flamel Tech Sa|Oral pharmaceutical formulation in the form of aqueous suspension of microcapsules for modified release of amoxicillim|

---

FR2842735B1|2002-07-26|2006-01-06|Flamel Tech Sa|MODIFIED RELEASE MICROCAPSULES OF LOW SOLUBLE ACTIVE PRINCIPLES FOR PER OS ADMINISTRATION|

---

FR2842736B1|2002-07-26|2005-07-22|Flamel Tech Sa|ORAL PHARMACEUTICAL FORMULATION IN THE FORM OF A PLURALITY OF MICROCAPSULES FOR PROLONGED RELEASE OF LOW SOLUBLE ACTIVEPRINCIPLE |

---

FR2843117B1|2002-07-30|2004-10-15|Flamel Tech Sa|POLYAMINOACIDS FUNCTIONALIZED BY AT LEAST ONE HYDROPHOBIC GROUP AND THEIR PARTICULARLY THERAPEUTIC APPLICATIONS|

---

US7632521B2|2003-07-15|2009-12-15|Eurand, Inc.|Controlled release potassium chloride tablets|

---

FR2860516B1|2003-10-03|2006-01-13|Flamel Tech Sa|TELECHELIC HOMOPOLYAMINOACIDES FUNCTIONALIZED BY HYDROPHOBIC GROUPS AND THEIR PARTICULARLY THERAPEUTIC APPLICATIONS|

---

FR2862536B1|2003-11-21|2007-11-23|Flamel Tech Sa|PHARMACEUTICAL FORMULATIONS FOR THE PROLONGED DELIVERY OF ACTIVEPRINCIPLEAND THEIR PARTICULARLY THERAPEUTIC APPLICATIONS|

---

US7244765B2|2004-06-25|2007-07-17|Cytokine Pharmasciences, Inc|Guanylhydrazone salts, compositions, processes of making and methods of using|

---

FR2885526B1|2005-05-13|2007-07-27|Flamel Technologies Sa|ORAL MEDICINE BASED ON PROTON PUMP INHIBITOR|

---

JP6184656B1|2015-10-13|2017-08-23|テクノガード株式会社|Gastrointestinal mucosa protective composition|

法律状态:

优先权:

---

申请号 | 申请日 | 专利标题

---

US06/180,537|US4321253A|1980-08-22|1980-08-22|Suspension of microencapsulated bacampicillin acid addition salt for oral, especially pediatric, administration|

---