EP0321457A4 - Dispersions aqueuses de cires et de lipides d'enrobages pharmaceutiques. - Google Patents

Dispersions aqueuses de cires et de lipides d'enrobages pharmaceutiques.

Info

Publication number
EP0321457A4
EP0321457A4 EP19870900713 EP87900713A EP0321457A4 EP 0321457 A4 EP0321457 A4 EP 0321457A4 EP 19870900713 EP19870900713 EP 19870900713 EP 87900713 A EP87900713 A EP 87900713A EP 0321457 A4 EP0321457 A4 EP 0321457A4
Authority
EP
European Patent Office
Prior art keywords
wax
coating
lipid
coating powder
process according
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Withdrawn
Application number
EP19870900713
Other languages
German (de)
English (en)
Other versions
EP0321457A1 (fr
Inventor
Suresh C Bagaria
Nicholas G Lordi
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.)
Research Corp
Original Assignee
Research Corp
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 Research Corp filed Critical Research Corp
Publication of EP0321457A4 publication Critical patent/EP0321457A4/fr
Publication of EP0321457A1 publication Critical patent/EP0321457A1/fr
Withdrawn legal-status Critical Current

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
    • A61K9/48—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
    • A61K9/5073—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 having two or more different coatings optionally including drug-containing subcoatings
    • A61K9/5078—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 having two or more different coatings optionally including drug-containing subcoatings with drug-free core
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23P—SHAPING OR WORKING OF FOODSTUFFS, NOT FULLY COVERED BY A SINGLE OTHER SUBCLASS
    • A23P20/00—Coating of foodstuffs; Coatings therefor; Making laminated, multi-layered, stuffed or hollow foodstuffs
    • A23P20/10—Coating with edible coatings, e.g. with oils or fats
    • A23P20/11—Coating with compositions containing a majority of oils, fats, mono/diglycerides, fatty acids, mineral oils, waxes or paraffins
    • 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

Definitions

  • This invention relates to aqueous dispersions of waxes and lipids for pharmaceutical coating and more particularly is concerned with the preparation of an aqueous system for the coating of pharmaceutical solids, i.e. medicaments and the like, with waxes or lipids alone or in combination.
  • the techniques employed for the application of wax and lipid coatings on solid dosage forms include the hot-melt e application whereby the waxes and lipids are melted with an oil-soluble emulsifying agent and are applied to tablets or granules rotating in a coating pan.
  • Another method in use employs organic solvent solutions of waxy materials in which the waxes and lipids Q are dissolved in a suitable organic solvent such as chloroform and the organic solution is then applied on tablets or pellets in a conventional coating pan, for example.
  • a suitable organic solvent such as chloroform
  • Spray, congealing is also in use and presents the 5 advantage of producing directly a free flowing powder by spraying a suspension of finely-divided powdered medicament, molten wax and lipid into solid particulate form.
  • Aqueous film coating has gained use recently.
  • a typical process involves dispersing a finely-divided powder 0 of hydroxypropylmethylcellulose phthalate in an aqueous medium containing triacetin to give an aqueous coating liquid, spraying the coating onto the surface of a solid dosage form and thereafter drying the thus coated solid dosage form to provide an enteric coating. 5 ⁇ None of these processes have been completely satisfactory.
  • Organic coating liquids are undesirable as the use of large amounts of organic solvents involves problems of explosion or fire hazard as well as possible toxic effects 5 and environmental pollution.
  • the hot-melt and spray congealing methods involve the use of special equipment which is costly.
  • the present invention involves a novel formulation and process for converting waxes and lipids used for 5 pharmaceutical and food coating encapsulation into a solid powder which can be reconstituted with water into an aqueous coating system for application as a protective, enteric and/or controlled release coating of drug-containing granules, pellets and tablets.
  • the aqueous dispersion method is a novel formulation and process for converting waxes and lipids used for 5 pharmaceutical and food coating encapsulation into a solid powder which can be reconstituted with water into an aqueous coating system for application as a protective, enteric and/or controlled release coating of drug-containing granules, pellets and tablets.
  • J_ Q of the present invention can be used to coat heat-sensitive materials as the product is not exposed to excessively high temperatures.
  • the present emulsion or dispersion system can be prepared with low viscosities at high solids content; such coating systems containing 20-30% solids can readily be— j_c j applied using conventional fluidized bed or pan-coating technology.
  • the novel aqueous film coating system of the present invention the coating thickness and uniformity of coating of drugs can be more effectively controlled and the 0 solid readily dispersible powdered form eliminates problems associated with shipping and shelf-stability of aqueous dispersions.
  • the present coating system may contain a wide range of wax and lipid materials alone or in combination. Pigments, plasticizers, both water and water-insoluble
  • polymers as well as drugs may easily be incorporated into the present coating system.
  • the present invention involves the emulsification of a lipid/wax mixture followed by spray drying to form a powder.
  • the resultant powder is readily dispersible in water and may be coated on drug-containing granules, pellets, tablets and the like.
  • the aqueous dispersions of waxes !_ and lipids may be used for pharma'ceutical coating applications of medicaments as, for instance, protective coatings, enteric coatings, sustained-release coatings and the like.
  • a typical formulation may include a lipid, i.e. partially hydrogenated cottonseed oil, an emulsifying agent, i.e., polysorbate, and/or a wax, i.e. castor wax.
  • the partially hydrogenated cottonseed oil may be heated in a water bath at 80-85°C.
  • a o solution of polysorbate (Tween 65) heated to 90°C. is then added to the molten lipid mass with constant stirring.
  • a dispersion of Veegum K in water heated to 90°C. is then added with stirring.
  • An antifoam agent for example, Antifoam AF, is added and made
  • ] _c up to weight by adding hot distilled water.
  • the emulsion is shock-cooled in an ice-bath with constant stirring.
  • a smooth emulsion having a particle size between 1-5 microns is obtained.
  • the emulsion may then be applied to the coating of
  • 2o pellets for example, by spray coating drug-coated non-pareil seeds in the coating vessel of a fluid-bed coating unit such as the Uni-Glatt in the usual manner.
  • the spraying is carried out continuously . until the desired increase in mean weight of drug-beads is achieved.
  • the wax component is employed in an amount of from about 10% to about 30%, and preferably from about 15% to about 20%, by weight, of the total quantity of the emulsion.
  • the lipid component when employed, is employed in an amount of from about 10% to about 30%, and preferably from about 15% to about 20%, by weight, of the total quantity of the emulsion.
  • the emulsifying agent is employed in an amount from about 0.5% to about 5%, and preferably from about 1% to about 3%, by weight, of the total quantity of the emulsion.
  • Water is employed in an amount sufficient to balance the formulation.
  • the wax component of the emulsion may comprise any ⁇ _0 paraffin wax obtained from petroleum oil and may include microcrystalline wax such as obtained from petroleum residues; also, paraffin waxes modified with various polymers, e.g. polyethylene, or copolymers such as ethylene-vinyl acetate copolymers and similar polymeri ⁇ - 2_ materials may be included.
  • paraffin v/ax having a melting point of from about 115°F. to about 150°F. is preferred, and such wax may comprise high molecular weight hydrocarbons, comprising, generally, straight-chain compounds having a crystalline structure in solid form. 2o Microcrystalline wax may be employed, as hereinbefore indicated, and is obtained from petroleum oil.
  • This material may possess a melting point of about 150°F. to about 190°F. and contains a substantial portion of high molecular weight hydrocarbons having branched-chain and ring structures.
  • This 2 material is more plastic in nature than paraffin wax.
  • Petrolatum is commercially obtained from petroleum and comprises a mixture of microcrystalline wax and petroleum oil.
  • Particularly useful waxes and lipids for use in the 0 present invention include:
  • Surface active agents for use in the present invention may be of the anionic or nonionic type.
  • the emulsifier employed in the wax/lipid emulsions of the present invention may be of the nonionic type and may also include
  • emulsifiers of the anionic type in combination therewith.
  • Many nonionic emulsifiers can be used in this emulsion provided the critical relationship between oil solubility and water solubility is maintained.
  • Typical of such emulsifiers are mixtures of sorbitan monooleate and poly ⁇ xyethylene
  • Typical other nonionic emulsifiers suitable for use in these wax/lipid emulsions are polyoxyethylene ethers of octyl or nonylphenol having variable amounts of ethylene oxide content per mole of finished product required to provide the oil and water 5 solubility characteristics.
  • polyoxyethylene ethers of octyl phenol having about 5 moles of ethylene oxide per mole of finished product when blended with a like amount of polyoxyethylene ethers of octyl phenol having about 10 moles of ethylene oxide per mole of finished 0 product provides an emulsifier combination having the desired water and oil solubility.
  • ethylene oxide content is reduced, oil solubility is enhanced, whereas as the ethylene oxide content is increased, water solubility 5 ] _ is enhanced.
  • a blended product having sufficient oil-soluble and water-soluble constituents and possessing an average ethylene oxide content per mole of finished product between about 5 and 10 is quite satisfactory.
  • Other nonionic emulsifiers contemplated within the scope of the present emulsions are exemplified by partial esters of fatty acids (e.g. palmitic, stearic, oleic and the like) and hexitol anhydrides (hexitans and hexides) derived from sorbitol.
  • Suitable deflocculating agents such as sodium hexametaphosphate, sodium tetraphosphate, sodium tripolyphosphate and potassium metaphosphate may advantageously be used in the present composition in amounts from about 0% to about 1% by weight.
  • Antifoam AF (Semithicon Emulsion) 10 Distilled Water q.s. 1000
  • the coating emulsion of the composition described in Example 1 is spray dried in a laboratory size spray dryer. j
  • the drying conditions selected are such that the spray drying chamber temperature is maintained at least 5°C. below the melting point of the wax.
  • a free-flowing powder is obtained with an average particle size of 1-5 micron.
  • 200 g of the above-described spray dried powder is dispersed in sufficient distilled water to give 500 g of final dispersion.
  • a suitable lab mixer such as a Brookfield mixer or Waring blender is used to ensure complete dispersion j_ of the spray dried powder in the aqueous media.
  • 500 g of drug granulation are placed in the coating vessel of a Uni-Glatt coater.
  • the above-described coating Q dispersion is sprayed continuously until the desired amount of lipid coat is applied.
  • the spray dried lipid emulsion, talc and _30 citroflex-4 are dispersed in distilled water with the help of a suitable lab mixer.
  • the resulting dispersion is passed through a homogenizer to ensure completeness of dispersion.
  • Drug-beads are coated in a fluid bed coating unit as described in Example 1.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Polymers & Plastics (AREA)
  • Food Science & Technology (AREA)
  • Medicinal Preparation (AREA)
EP87900713A 1986-01-13 1987-01-09 Dispersions aqueuses de cires et de lipides d'enrobages pharmaceutiques Withdrawn EP0321457A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US81845586A 1986-01-13 1986-01-13
US818455 1986-01-13

Publications (2)

Publication Number Publication Date
EP0321457A4 true EP0321457A4 (fr) 1988-11-24
EP0321457A1 EP0321457A1 (fr) 1989-06-28

Family

ID=25225582

Family Applications (1)

Application Number Title Priority Date Filing Date
EP87900713A Withdrawn EP0321457A1 (fr) 1986-01-13 1987-01-09 Dispersions aqueuses de cires et de lipides d'enrobages pharmaceutiques

Country Status (2)

Country Link
EP (1) EP0321457A1 (fr)
WO (1) WO1987004070A1 (fr)

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4894231A (en) * 1987-07-28 1990-01-16 Biomeasure, Inc. Therapeutic agent delivery system
WO1992001446A1 (fr) * 1990-07-20 1992-02-06 Aps Research Limited Formulations a liberation entretenue
WO1992009275A1 (fr) * 1990-11-30 1992-06-11 Yamanouchi Pharmaceutical Co., Ltd. Preparation enrobee a liberation rapide
FR2779651B1 (fr) * 1998-06-16 2001-04-20 Gattefosse Ets Sa Procede pour la fabrication de comprimes a liberation prolongee de principe(s) actif(s) presentant une cinetique de dissolution d'ordre zero
US7267743B2 (en) 2003-03-17 2007-09-11 Marcus Oil And Chemical Wax emulsion coating applications
US7776928B2 (en) * 2003-03-17 2010-08-17 Hrd Corp. Wax emulsion coating applications
ITMI20041820A1 (it) * 2004-09-24 2004-12-24 Ascor Chimici Srl Composizione in micro-pellets a rilascio controllato di sostanze fisiologicamente attive, procedimento di preparazione e relativo impiego nel settore zootecnico.
WO2006048895A1 (fr) * 2004-11-08 2006-05-11 Rubicon Research Pvt. Ltd. Revetement pharmaceutique aqueux
FR3017775A1 (fr) * 2014-02-21 2015-08-28 Denis Et Fils Sas Cire a greffer pulverulente.
WO2023150072A1 (fr) 2022-02-01 2023-08-10 Sinclair David A Compositions et procédés de conservation de matière végétale

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2404029A1 (fr) * 1977-09-26 1979-04-20 Sankyo Co Composition d'enrobage pouvant etre ingeree

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3438797A (en) * 1965-10-21 1969-04-15 Jerry Allen Biddle Sr Method of preparing pharmaceutical tablets
US3935326A (en) * 1967-06-28 1976-01-27 Boehringer Mannheim G.M.B.H. Process for coating tablets with aqueous resin dispersions
FR2521565B1 (fr) * 1982-02-17 1985-07-05 Dior Sa Parfums Christian Melange pulverulent de constituants lipidiques et de constituants hydrophobes, procede pour le preparer, phases lamellaires lipidiques hydratees et procede de fabrication, compositions pharmaceutiques ou cosmetiques comportant des phases lamellaires lipidiques hydratees

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2404029A1 (fr) * 1977-09-26 1979-04-20 Sankyo Co Composition d'enrobage pouvant etre ingeree

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
CHEMICAL ABSTRACTS, vol. 89, no. 20, 13th November 1978, page 359, résumé no. 169098m, Columbus, Ohio, US; & JP-A-78 62 821 (TAKEDA CHEMICAL INDUSTRIES LTD) 05-06-1978 *
CHEMICAL ABSTRACTS, vol. 92, no. 22, 2nd June 1980, page 302, résumé no. 185917v, Columbus, Ohio, US; & JP-A-79 143 518 (F. SEKIKAWA et al.) 08-11-1979 *
See also references of WO8704070A1 *

Also Published As

Publication number Publication date
EP0321457A1 (fr) 1989-06-28
WO1987004070A1 (fr) 1987-07-16

Similar Documents

Publication Publication Date Title
US5023108A (en) Aqueous dispersions of waxes and lipids for pharmaceutical coating
Thies Microencapsulation
Jannin et al. Hot-melt coating with lipid excipients
Murtaza Ethylcellulose microparticles: A review
EP0129365B1 (fr) Enrobage entérique pour des formes de dosage pharmaceutiques
US6544646B2 (en) Zero order release and temperature-controlled microcapsules and process for the preparation thereof
US3265629A (en) Coating by phase separation
FI119720B (fi) Pitkävaikutteisten rakeisten valmisteiden valmistusmenetelmä
US7897179B2 (en) Pharmaceutical composition containing water soluble drug
US6238704B1 (en) Sustained-release preparation utilizing thermal change and process for the production thereof
Garg et al. Microencapsulation techniques in pharmaceutical formulation
WO2001056545A2 (fr) Systeme d'administration microencapsule a liberation prolongee
EP0013566A2 (fr) Méthode pour enduire des formes de dosage solides d'une couche entérique
IE911276A1 (en) Granulated preparations and method of producing the same
WO1987004070A1 (fr) Dispersions aqueuses de cires et de lipides d'enrobages pharmaceutiques
KR20080074083A (ko) 난용성 약물을 포함하는 의약용 고형 제제와 그의 제조방법
KR100420269B1 (ko) 무용매로코팅된고형제제및그후처리방법
AU2006331009A1 (en) Masking the taste of powders
EA000467B1 (ru) Гранулированный препарат и способ его получения
Lehmann Fluid-bed spray coating
US3379554A (en) Spray coating of pharmaceutical cores with a carboxylvinyl polymer and polyethylene glycol
EP0745383B1 (fr) Procédé de fabrication d'une préparation entérique enrobée d'une substance d'enrobage en poudre en utilisant un plastifiant liquide
CN1960716B (zh) 口服制剂及其制造方法
JP2506048B2 (ja) カプセル含有浴用剤組成物
JPH0138091B2 (fr)

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 19880713

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE CH DE FR GB IT LI LU NL SE

17Q First examination report despatched

Effective date: 19911025

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 19920702

RIN1 Information on inventor provided before grant (corrected)

Inventor name: BAGARIA, SURESH, C.

Inventor name: LORDI, NICHOLAS, G.