US20020187196A1 - Micro-capsules for the sustained release of drugs - Google Patents

Micro-capsules for the sustained release of drugs Download PDF

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Publication number
US20020187196A1
US20020187196A1 US09/913,671 US91367101A US2002187196A1 US 20020187196 A1 US20020187196 A1 US 20020187196A1 US 91367101 A US91367101 A US 91367101A US 2002187196 A1 US2002187196 A1 US 2002187196A1
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US
United States
Prior art keywords
pharmaceutical preparation
micro
pharmaceutical
capsules
analogue
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.)
Abandoned
Application number
US09/913,671
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English (en)
Inventor
Antonio Duena
Josep Garces
Angel Munoz
David Colome
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
GP Pharm SA
Original Assignee
Lipotec SA
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Lipotec SA filed Critical Lipotec SA
Assigned to LIPOTEC, S.A. reassignment LIPOTEC, S.A. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: BONILLA MUNOZ, ANGEL, CUMILLERA COLOME, DAVID, GARCES GARCES, JOSEO, PARENTE DUENA, ANTONIO
Publication of US20020187196A1 publication Critical patent/US20020187196A1/en
Priority to US12/148,893 priority Critical patent/US9789064B2/en
Assigned to GP PHARM, S.A. reassignment GP PHARM, S.A. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: LIPOTEC, S.A.
Abandoned legal-status Critical Current

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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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1641—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
    • A61K9/1647—Polyesters, e.g. poly(lactide-co-glycolide)
    • 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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1617—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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005—Wall or coating material
    • A61K9/5015—Organic compounds, e.g. fats, sugars
    • 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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005—Wall or coating material
    • A61K9/5021—Organic macromolecular compounds
    • A61K9/5031—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poly(lactide-co-glycolide)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/02—Drugs for disorders of the endocrine system of the hypothalamic hormones, e.g. TRH, GnRH, CRH, GRH, somatostatin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/18—Drugs for disorders of the endocrine system of the parathyroid hormones
    • A61P5/22—Drugs for disorders of the endocrine system of the parathyroid hormones for decreasing, blocking or antagonising the activity of calcitonin

Definitions

  • the present invention relates to a new type of micro-capsule or micro-bead for the sustained administration of drugs and to a procedure for their preparation.
  • modulating release from microcapsules is understood to mean a reduction in the initial release of encapsulated drug and a release of said drug that is almost linear in time. It is both surprising and unexpected, in view of that described by Pitt et al. that the incorporation of small amounts of citric acid ester into the microcapsule preparation of lactic-co-glycolic polymer that encapsulate a peptide of pharmaceutical interest allows the release of the drug to be almost linear and without the presence of sudden initial releases of the drug.
  • the object of this invention consists of providing pharmaceutical of prepartions micro-capsules of polymers of lactic and glycolic acid plastified with small quantities of citric acid esters and which contain peptides.
  • the present invention also comprises the preparation and use of the aforementioned microcapsules.
  • the citric acid esters useful for the purposes of the present invention are those normally used as plasticizers for pharmaceutical polymers, such as triethyl citrate, tributyl citrate and acetyl tributyl citrate. Use of triethyl citrate is preferable.
  • analogues of LHRH such as tryptoreline, leuprolide, gosereline, busereline or cetrorelix
  • analogues of somatostatin such as somatostatin or octreotide
  • analogues of human calcitonin such as salmon calcitonin or carbocalcitonin.
  • micro-capsules can be carried out following any of the methods described in the literature such as, for example, those described in the U.S. Pat. No. 3,773,919.
  • the different procedures for producing micro-capsules of the invention would be grouped into the following sections:
  • a solution of polymer is prepared along with tri-ethyl citrate in a suitable solvent.
  • the drug to be encapsulated is suspended in the polymer and plasticiser solution and a non-solvent of the polymer is added to force deposition of the polymer on the drug crystals. Examples of these procedures without using plasticiser can also be found in documents such as ES 2009346 or EP 052 510.
  • the drug to be encapsulated is dissolved in water or in a solution of some other co-adjuvant in is emulsified in a solution of the polymer and the plasticiser in a suitable solvent such as dichloromethane for example.
  • the resulting emulsion is in turn emulsified in water or in an aqueous solution of an emulsifier such as polyvinylic alcohol.
  • an emulsifier such as polyvinylic alcohol.
  • the drug to be encapsulated, the polymer and the plasticiser are dissolved together in a suitable solvent.
  • This solution is emulsified in water or a solution of an emulsifier such as polyvinyl acid and the organic solvent eliminated by evaporation or extraction.
  • the resulting micro-capsules are recovered by filtration. Examples of these procedures that do not sue the plasticiser can also be found in documents such as U.S. Pat. No. 5,445,832.
  • the citric acid ester is deposited along with the polymer, plastifying it and advantageously modifying the hydrophobicity, flexibility and coating capacity characteristics of the polymer and the release profile of the micro-capsules obtained.
  • micro-capsules are recovered by filtration and dried under vacuum for 48 hours.
  • micro-capsules are recovered by filtration and dried under vacuum for 48 hours.
  • micro-capsules are recovered by filtration and dried under vacuum for 48 hours.
  • each tube is gently shaken to suspend the micro-capsules in the buffer, the tubes are sealed and placed in an oven at 37° C.
  • ELUENT Acetonitrile/water 30/70+0.05% trifluoracetic acid
  • FIG. 1 The result of this analysis is indicated in FIG. 1.
  • the results obtained are compared with a control assay performed with leuprolide microcapsules in which diethyl citrate has not been incorporated, in accordance with the method of example 1.

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  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Endocrinology (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Diabetes (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
US09/913,671 1999-12-17 2000-12-15 Micro-capsules for the sustained release of drugs Abandoned US20020187196A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US12/148,893 US9789064B2 (en) 1999-12-17 2008-04-23 Method for delivering a peptide to a subject at a modulated rate via microcapsules of lactic-co-glycolic copolymer containing said peptide

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
ES009902768A ES2169980B1 (es) 1999-12-17 1999-12-17 Microcapsulas para la liberacion prolongada de farmacos.
ESP9902768 1999-12-17

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US11/042,682 Division US20050123618A1 (en) 1999-12-17 2005-01-25 Method of producing micro-capsules for the sustained release of drugs

Publications (1)

Publication Number Publication Date
US20020187196A1 true US20020187196A1 (en) 2002-12-12

Family

ID=8310957

Family Applications (3)

Application Number Title Priority Date Filing Date
US09/913,671 Abandoned US20020187196A1 (en) 1999-12-17 2000-12-15 Micro-capsules for the sustained release of drugs
US11/042,682 Abandoned US20050123618A1 (en) 1999-12-17 2005-01-25 Method of producing micro-capsules for the sustained release of drugs
US12/148,893 Expired - Fee Related US9789064B2 (en) 1999-12-17 2008-04-23 Method for delivering a peptide to a subject at a modulated rate via microcapsules of lactic-co-glycolic copolymer containing said peptide

Family Applications After (2)

Application Number Title Priority Date Filing Date
US11/042,682 Abandoned US20050123618A1 (en) 1999-12-17 2005-01-25 Method of producing micro-capsules for the sustained release of drugs
US12/148,893 Expired - Fee Related US9789064B2 (en) 1999-12-17 2008-04-23 Method for delivering a peptide to a subject at a modulated rate via microcapsules of lactic-co-glycolic copolymer containing said peptide

Country Status (13)

Country Link
US (3) US20020187196A1 (ja)
EP (1) EP1151746B1 (ja)
JP (1) JP5021880B2 (ja)
AT (1) ATE234608T1 (ja)
AU (1) AU774680B2 (ja)
BR (1) BRPI0008197B8 (ja)
CA (1) CA2362769C (ja)
DE (1) DE60001717T2 (ja)
DK (1) DK1151746T3 (ja)
ES (2) ES2169980B1 (ja)
MX (1) MXPA01008348A (ja)
PT (1) PT1151746E (ja)
WO (1) WO2001043724A1 (ja)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040097419A1 (en) * 2002-11-19 2004-05-20 Holger Petersen Organic compounds
US20110124563A1 (en) * 2007-11-23 2011-05-26 Gp Pharm S.A. Pharmaceutical composition with prolonged release of somatostatin or an analogue thereof
CN110954491A (zh) * 2019-12-09 2020-04-03 北京博恩特药业有限公司 用于测量醋酸戈舍瑞林缓释植入剂体外溶出度的方法

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20090110744A1 (en) * 2005-03-01 2009-04-30 Sun Pharma Advanced Research Company Limited Sustained release pharmaceutical compositions
KR20140133968A (ko) * 2005-12-22 2014-11-20 노파르티스 아게 옥트레오티드 및 ２종 이상의 폴리락티드-코-글리콜리드 중합체를 포함하는 서방형 제제
CN105267153B (zh) * 2015-11-27 2018-05-11 上海苏豪逸明制药有限公司 一种曲普瑞林缓释微粒及其制备方法
JP7371519B2 (ja) 2020-02-14 2023-10-31 村田機械株式会社 自動倉庫

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US3773919A (en) 1969-10-23 1973-11-20 Du Pont Polylactide-drug mixtures
EP0052610A1 (en) 1980-05-29 1982-06-02 NICKLAUS, Helen Carol Stringed musical instrument teaching device and process
GB2132887A (en) * 1982-11-15 1984-07-18 Procter & Gamble Enteric-coated anti-inflammatory compositions
CH661206A5 (fr) 1983-09-23 1987-07-15 Debiopharm Sa Procede pour la preparation d'un medicament destine au traitement de maladies hormonodependantes.
JPS60100516A (ja) 1983-11-04 1985-06-04 Takeda Chem Ind Ltd 徐放型マイクロカプセルの製造法
ATE61935T1 (de) 1985-02-07 1991-04-15 Takeda Chemical Industries Ltd Verfahren zur herstellung von mikrokapseln.
JP2551756B2 (ja) 1985-05-07 1996-11-06 武田薬品工業株式会社 ポリオキシカルボン酸エステルおよびその製造法
CH665558A5 (en) 1985-10-09 1988-05-31 Debiopharm Sa Phase sepn. prodn. of microcapsules for water soluble pharmaceuticals - using fluoro-substd. aliphatic hydrocarbon as non-solvent in the hardening stage
GB2209937B (en) 1987-09-21 1991-07-03 Depiopharm S A Water insoluble polypeptides
US5538739A (en) * 1989-07-07 1996-07-23 Sandoz Ltd. Sustained release formulations of water soluble peptides
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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040097419A1 (en) * 2002-11-19 2004-05-20 Holger Petersen Organic compounds
US20070122485A1 (en) * 2002-11-19 2007-05-31 Holger Petersen Organic compounds
US20110124563A1 (en) * 2007-11-23 2011-05-26 Gp Pharm S.A. Pharmaceutical composition with prolonged release of somatostatin or an analogue thereof
CN110954491A (zh) * 2019-12-09 2020-04-03 北京博恩特药业有限公司 用于测量醋酸戈舍瑞林缓释植入剂体外溶出度的方法

Also Published As

Publication number Publication date
US20050123618A1 (en) 2005-06-09
CA2362769A1 (en) 2001-06-21
DK1151746T3 (da) 2003-07-21
EP1151746A1 (en) 2001-11-07
DE60001717T2 (de) 2004-03-18
BRPI0008197B1 (pt) 2017-05-09
US9789064B2 (en) 2017-10-17
US20080233198A1 (en) 2008-09-25
AU2173501A (en) 2001-06-25
JP2003516960A (ja) 2003-05-20
AU774680B2 (en) 2004-07-01
WO2001043724A1 (es) 2001-06-21
ES2169980B1 (es) 2003-11-01
DE60001717D1 (de) 2003-04-24
ES2169980A1 (es) 2002-07-16
CA2362769C (en) 2008-09-09
BRPI0008197B8 (pt) 2021-05-25
JP5021880B2 (ja) 2012-09-12
BR0008197A (pt) 2002-01-22
PT1151746E (pt) 2003-07-31
ES2194793T3 (es) 2003-12-01
ATE234608T1 (de) 2003-04-15
EP1151746B1 (en) 2003-03-19
MXPA01008348A (es) 2004-03-19

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AS Assignment

Owner name: LIPOTEC, S.A., SPAIN

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:PARENTE DUENA, ANTONIO;GARCES GARCES, JOSEO;BONILLA MUNOZ, ANGEL;AND OTHERS;REEL/FRAME:012293/0555

Effective date: 20010731

STCB Information on status: application discontinuation

Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION

AS Assignment

Owner name: GP PHARM, S.A., SPAIN

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:LIPOTEC, S.A.;REEL/FRAME:028554/0529

Effective date: 20120712