WO2011084618A2 - Compositions et procédés d'administration de médicaments par voie orale - Google Patents

Compositions et procédés d'administration de médicaments par voie orale Download PDF

Info

Publication number
WO2011084618A2
WO2011084618A2 PCT/US2010/060809 US2010060809W WO2011084618A2 WO 2011084618 A2 WO2011084618 A2 WO 2011084618A2 US 2010060809 W US2010060809 W US 2010060809W WO 2011084618 A2 WO2011084618 A2 WO 2011084618A2
Authority
WO
WIPO (PCT)
Prior art keywords
pharmaceutical composition
layer
exenatide
bioadhesive
tablets
Prior art date
Application number
PCT/US2010/060809
Other languages
English (en)
Other versions
WO2011084618A3 (fr
Inventor
William W. Lee
Feng Lu
Yin Min
Liuying Shao
Hao SHE
Zhou Shen
Original Assignee
Nod Pharmaceuticals, Inc.
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
Priority claimed from CN200910201248.3A external-priority patent/CN102100912B/zh
Priority claimed from CN201010227045.4A external-priority patent/CN102335431B/zh
Application filed by Nod Pharmaceuticals, Inc. filed Critical Nod Pharmaceuticals, Inc.
Priority to CA2784120A priority Critical patent/CA2784120A1/fr
Priority to AU2010339907A priority patent/AU2010339907A1/en
Priority to EP10795591A priority patent/EP2512454A2/fr
Priority to JP2012544835A priority patent/JP2013514976A/ja
Publication of WO2011084618A2 publication Critical patent/WO2011084618A2/fr
Publication of WO2011084618A3 publication Critical patent/WO2011084618A3/fr

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
    • A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/22—Hormones
    • A61K38/2278—Vasoactive intestinal peptide [VIP]; Related peptides (e.g. Exendin)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/22—Hormones
    • A61K38/28—Insulins
    • 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
    • A61K9/284—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone
    • A61K9/2846—Poly(meth)acrylates
    • 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
    • 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
    • A61K9/2886—Dragees; Coated pills or tablets, e.g. with film or compression coating having two or more different drug-free coatings; Tablets of the type inert core-drug layer-inactive layer
    • 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
    • A61K9/2893—Tablet coating processes
    • 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

Definitions

  • permeation enhancers are commonly used to enhance the absorption of drugs that are otherwise poorly absorbed (for a review, see B.J. Aungst, J. Pharm. Sci., 2000, 89(4):429-442). Numerous examples of permeation enhancers that are known to improve transdermal or transmucosal absorption are disclosed in U.S. Patent Nos.
  • the invention provides a pharmaceutical composition for drug delivery comprising a solid dosage form containing an effective amount of a therapeutic agent, a permeation enhancer and a pharmaceutically acceptable excipient, to form a core, which is coated by a bioadhesive layer containing a bioadhesive polymer.
  • the order of applying the bioadhesive polymer layer and the impermeable or semi-permeable layer is reversed.
  • the method further comprises coating the composition with an enteric layer.
  • FIGS. 14A and 14B demonstrate the effect of bioadhesive polymer content in the bioadhesive layer on the kinetics of exenatide release and absorption in normal dogs.
  • the exenatide formulations used for this experiment were two-layer tablets that included 100 mg sodium caprate, an HPMC layer containing 65% or 80% HPMC and the L30D-55 enteric material, and a unidirectional release layer prepared by laser ablation.
  • composition or “pharmaceutically acceptable formulation” refers to a composition or formulation that allows for the effective distribution of a moiety or a compound in the physical location most suitable for its desired activity.
  • the term “treating” refers to any and all uses which remedy or prevent a diseased or infected state or symptoms, or otherwise deter, hinder, retard, or reverse the progression of a disease/infection or other undesirable symptoms.
  • the terms “treating” and “therapeutic” refer to any improvement or amelioration of any consequence of disease; full eradication of disease is not required.
  • Amelioration of symptoms of a particular disorder refers to any lessening of symptoms, whether permanent or temporary, that can be attributed to or associated with administration of a therapeutic composition of the present invention.
  • solid dosage form refers to any dosage form that is in the form of a solid including, but not limited to, tablets, caplets, capsules including those made from hard or soft materials such as gelatin or natural or synthetic gelatin substitutes, lozenges, combinations thereof and the like.
  • eflornithine an enalapril, an enprostil, an epinephrine, an ergometrine, an erlotinib, an erythromycin, an esomeprazole, an estradiol, an eszopiclone, an etoposide, an ezetimibe, a famotidine, a felodipine, a fenofibrate, a fentanyl, a fexofenadine, a finasteride, a flucytosine, a fludrocortisones, a fluorouracil, a fluoxetine, a fluphenazine, a flurbiprofen, a fluticasone, a fluvastatin, a formoterol, a furosemide, a gabapentin, a ganciclovir, a gemcitabine, a gentamicin, a glib
  • the pharmaceutical compositions may include other components, such as buffers, preservatives, nonionic surfactants, solubilizing agents, absorption enhancers, stabilizing agents, emollients, lubricants and tonicity agents.
  • the composition may be formulated to achieve controlled release of the drugs.
  • the pharmaceutical compositions may be in a form suitable for oral use, for example, as tablets, troches, lozenges, or hard or soft capsules.
  • Compositions intended for oral use may be prepared according to any method known in the art for the manufacture of pharmaceutical compositions and such compositions may contain one or more agents such as sweetening agents, flavoring agents, coloring agents and preserving agents, e.g. to provide pharmaceutically stable and palatable preparations.
  • the amount of permeation enhancer, particularly sodium caprate, in the formulation is about 400 mg, about 300 mg, about 200 mg, about 100 mg, about 50 mg, or about 25 mg, preferably about 200 mg, about 100 mg, or about 50 mg, and more preferably about 100 mg.
  • the content of sodium caprate ranges between about 25-300 mg, about 50-200 mg, or about 100-200 mg.
  • compositions of the present invention may also be any pharmaceutical compositions of the present invention.
  • pharmaceutical compositions of the present invention may also be any pharmaceutical compositions of the present invention.
  • compositions for the administration of the compounds of the invention may conveniently be presented in dosage unit form and may be prepared by any of the methods well known in the art of pharmacy.
  • the core pharmaceutical composition of the present invention is coated with a bioadhesive layer comprising a bioadhesive polymer.
  • the bioadhesive layer comprises a composite of materials, such as a bioadhesive polymer, a plasticizer, or other materials to module the release rate. It is desirable to have high content of bioadhesive materials. In some embodiments, the content of a bioadhesive polymer comprises above about 50%, above about 65%, above about 75%, above about 80%, or above about 90%.
  • enteric material in the bioadhesive layer may preserve integrity of the dosage in the stomach and allow release and absorption in the intestines where pH is raised. It often requires high proportion of enteric material such as about 50% or more in order to maintain acid stability. It is therefore quite surprising to observe the acid stability of the dosage even with enteric material as low as about 10-20%.
  • the of the unidirectional release tablet opening of the unidirectional release tablet can have any shape, for example, a circle, a triangle, a square, a rectangle, a rhombus, a parallelogram, a trapezium, or any other shape.
  • copolymers ethylene/vinyl acetate, polypropylene, polyurethane, ethylene/vinyl alcohol, polyvinyl alcohol, polyvinyllidene, polyolefin, or any combination thereof.
  • the solid dosage form includes an exendin or an exendin peptide analog as the therapeutic agent and sodium caprate as the permeation enhancer;
  • the bioadhesive layer includes HPMC or AA1 as the bioadhesive polymer and EUDRAGIT® L30D-55 as the enteric polymer;
  • the semi-permeable layer includes cellulose acetate or ethyl cellulose and an opening allowing unidirectional release.
  • the bioadhesive layer comprises at least about 70% bioadhesive polymer by weight of the layer and at least about 5% enteric polymer by weight of the layer.
  • the amount of sodium caprate ranges between about 100 and 150 mg.
  • the present invention provides a method for making the present pharmaceutical composition comprising of the following steps: fabricating a solid dosage form comprising an effective amount of a therapeutic agent, a permeation enhancer and a pharmaceutically acceptable excipient; coating the solid dosage form with a bioadhesive layer comprising a bioadhesive polymer; and optionally coating the solid dosage form with an impermeable or semi-permeable layer comprising an opening capable of directing a substantially unidirectional release of the therapeutic agent and the permeation enhancer from the solid dosage form.
  • the order of applying the bioadhesive polymer layer and the impermeable or semi-permeable layer is reversed.
  • the pharmaceutical composition of present invention is produced in the form of tablets or caplets.
  • the core tablets are formed by compression, commonly achieved with a rotary press.
  • the tablet fabrication processes including wet granulation and direct compression, have been amply described and are well known art. (DEVELOPING SOLID ORAL DOSAGE FORMS: PHARMACEUTICAL THEORY AND PRACTICE, Ed. by Qiu et al., Academic Press 2009).
  • the development of tablet form for macromolecular drugs remains challenging. Most macromolecular drugs are peptides and proteins, which have delicate structure and are highly unstable.
  • Table 4 shows the fractions of exenatide or sodium caprate released from the tablets coated with enteric polymer, ethyl cellulose, and HPMC containing 50 mg sodium caprate. The results are also summarized in FIG. 2B. As in the previous experiment, the release of exenatide and sodium caprate is substantially synchronous. Notably, release from the ethyl cellulose coated tablets is further extended compared to the tablets containing a cellulose acetate layer (maximum release reached at 5 hrs vs. 3 hrs).
  • the core tablets were fabricated according to the formula listed in Table 15 by compression using a single tablet press. All the components except exenatide and magnesium stearate were first weighed and mixed thoroughly. Granules were then formed with 15% polyvinylpyrrolidone (PVP) in 25% ethanol as adhesive material and dried under vacuum overnight. The granules were sieved through a 22-mesh screen and weighed based on the single tablet along with exenatide and magnesium stearate. The composition was mixed and pressed into tablets. All tablets were weighed individually, and those tablets with more than 5% deviation from the mean tablet weight were excluded from further experiments.
  • PVP polyvinylpyrrolidone
  • the core tablets were coated with hydroxypropyl methylcellulose (HPMC) with or without enteric material EUDRAGIT® L30D-55.
  • HPMC hydroxypropyl methylcellulose
  • EUDRAGIT® L30D-55 enteric material EUDRAGIT® L30D-55
  • an aqueous solution of 6% HPMC and 1.5% polyethylene glycol, MW 6000 (PEG 6000) was used in a tablet pan coater (BY300A, Yellow Sea Machinery).
  • the weight gain due to the bioadhesive layer was 3-4 mg.
  • For coating with L30D-55 an aqueous solution of 3% HPMC and 0.6% L30D-55 was used in the tablet pan coater.
  • the coated tablets were dried at 40°C for about 14 hrs.
  • the weight gain due to the bioadhesive layer was 3 mg.
  • the tablets coated with a bioadhesive layer were subsequently coated with a semi -permeable cellulose acetate layer.
  • the tablets with diameter of 9 mm were first covered on one side with adhesive paper having circular shape of 7 mm diameter.
  • the tablets were coated in a pan coater with a unidirectional coating solution containing 3% cellulose acetate and 1.2% polyethylene glycol, MW 2000 (PEG 2000) in a mixture of acetone and formic acid (9: 1 v/v) and dried at 40°C overnight.
  • the weight gain due to the unidirectional release layer was 2 mg.
  • the circular sticker was peeled off to expose the unidirectional release opening.
  • the tablets coated with a bioadhesive layer were subsequently coated with a semi-permeable cellulose acetate layer.
  • the 10 mm diameter tablets were first covered on one side with circular stickers of 7 mm diameter.
  • the tablets were coated in a pan coater with a unidirectional coating solution containing 3% cellulose acetate and 1.2% polyethylene glycol, MW 2000 (PEG 2000) in a mixture of acetone and formic acid (9: 1 v/v).
  • the tablets were dried at 40°C overnight after coating was completed.
  • the weight gain due to the unidirectional release layer was 2 mg.
  • the adhesive paper was peeled off to expose the unidirectional release openings.
  • Table 20 Core tablet formulation (amounts shown in milligrams).
  • Blend uniformities of insulin and exenatide were evaluated according to U.S. Pharmacopeia General Chapter ⁇ 905>, "Uniformity of Dosage Units" ("USP ⁇ 905>”), and samples of the same weight (equal to that of a tablet) were collected from different locations after the blends were mixed completely. Insulin or exenatide content was measured by RP- HPLC. The blend uniformity results are shown in the Table 21.
  • Table 29 Basic core tablet formulation (amounts shown in milligrams).

Abstract

Cette invention concerne une composition pharmaceutique pour l'administration de médicaments par voie orale comprenant une forme pharmaceutique solide contenant une quantité efficace d'un agent thérapeutique, un promoteur de perméation et un excipient pharmaceutiquement acceptable et une couche bioadhésive contenant un polymère bioadhésif, et comprenant, éventuellement, une couche imperméable ou semi-perméable comportant une ouverture capable d'orienter la libération unidirectionnelle de l'agent thérapeutique et du promoteur de perméation à partir de la forme pharmaceutique solide. Des procédés de préparation et d'utilisation de la présente composition pharmaceutique sont également décrits.
PCT/US2010/060809 2009-12-16 2010-12-16 Compositions et procédés d'administration de médicaments par voie orale WO2011084618A2 (fr)

Priority Applications (4)

Application Number Priority Date Filing Date Title
CA2784120A CA2784120A1 (fr) 2009-12-16 2010-12-16 Compositions et procedes d'administration de medicaments par voie orale
AU2010339907A AU2010339907A1 (en) 2009-12-16 2010-12-16 Compositions and methods for oral drug delivery
EP10795591A EP2512454A2 (fr) 2009-12-16 2010-12-16 Compositions et procedes d'administration de medicaments par voie orale
JP2012544835A JP2013514976A (ja) 2009-12-16 2010-12-16 経口薬物送達のための組成物および方法

Applications Claiming Priority (8)

Application Number Priority Date Filing Date Title
US28714609P 2009-12-16 2009-12-16
US61/287,146 2009-12-16
CN200910201248.3A CN102100912B (zh) 2009-12-16 2009-12-16 一种给药组合物及其制备和使用方法
CN200910201248.3 2009-12-16
CN201010227045.4 2010-07-14
CN201010227045.4A CN102335431B (zh) 2010-07-14 2010-07-14 一种给药组合物及其制备和使用方法
US36591610P 2010-07-20 2010-07-20
US61/365,916 2010-07-20

Publications (2)

Publication Number Publication Date
WO2011084618A2 true WO2011084618A2 (fr) 2011-07-14
WO2011084618A3 WO2011084618A3 (fr) 2012-01-19

Family

ID=44306059

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2010/060809 WO2011084618A2 (fr) 2009-12-16 2010-12-16 Compositions et procédés d'administration de médicaments par voie orale

Country Status (5)

Country Link
EP (1) EP2512454A2 (fr)
JP (1) JP2013514976A (fr)
AU (1) AU2010339907A1 (fr)
CA (1) CA2784120A1 (fr)
WO (1) WO2011084618A2 (fr)

Cited By (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2014520889A (ja) * 2011-07-19 2014-08-25 バクスター・インターナショナル・インコーポレイテッド 非抗凝固性硫酸化多糖の経口製剤を改善するための添加剤としての吸収促進剤
WO2015010927A1 (fr) * 2013-07-24 2015-01-29 Novo Nordisk A/S Composition pharmaceutique pour administration orale d'insuline comprenant un cœur de comprimé et un enrobage de copolymère anionique
CN104998251A (zh) * 2015-07-08 2015-10-28 哈尔滨吉象隆生物技术有限公司 用于口服肠溶制剂制备的具有促肠吸收作用的利拉鲁肽盐
CN105079793A (zh) * 2015-07-18 2015-11-25 哈尔滨吉象隆生物技术有限公司 一种可用于口服的利拉鲁肽与盐酸二甲双胍复方制剂
CN105079794A (zh) * 2015-07-18 2015-11-25 哈尔滨吉象隆生物技术有限公司 一种可用于口服的利拉鲁肽与磺脲类复方制剂
US9278123B2 (en) 2010-12-16 2016-03-08 Novo Nordisk A/S Solid compositions comprising a GLP-1 agonist and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid
WO2016119854A1 (fr) * 2015-01-29 2016-08-04 Novo Nordisk A/S Composition pharmaceutique pour l'administration d'insuline par voie orale comprenant un noyau de comprimé et un enrobage d'alcool polyvinylique
JP2016155811A (ja) * 2010-01-28 2016-09-01 メリオン・リサーチ・Ｉｉｉ・リミテッド 増強剤を含む固形医薬組成物およびその調製方法
RU2617049C1 (ru) * 2016-05-12 2017-04-19 Федеральное государственное бюджетное учреждение "Национальный исследовательский центр "Курчатовский институт" Противоопухолевое лекарственное средство на основе никлозамида
EP3121195A4 (fr) * 2014-03-21 2017-10-11 Anygen Co., Ltd. Nouvel analogue de l'exénatide et son utilisation
US9993430B2 (en) 2012-06-20 2018-06-12 Novo Nordisk A/S Tablet formulation comprising semaglutide and a delivery agent
US10265384B2 (en) 2015-01-29 2019-04-23 Novo Nordisk A/S Tablets comprising GLP-1 agonist and enteric coating
US10335369B2 (en) 2012-03-22 2019-07-02 Novo Nordisk A/S Compositions comprising a delivery agent and preparation thereof
US10933120B2 (en) 2012-03-22 2021-03-02 Novo Nordisk A/S Compositions of GLP-1 peptides and preparation thereof
US11034746B2 (en) 2011-04-12 2021-06-15 Novo Nordisk A/S Double-acylated GLP-1 derivatives
US11123296B2 (en) 2012-03-22 2021-09-21 Novo Nordisk A/S Compositions comprising a delivery agent and preparation thereof
US11548940B2 (en) 2014-05-15 2023-01-10 Rani Therapeutics, Llc Anti-interleukin antibody preparations for delivery into a lumen of the intestinal tract using a swallowable drug delivery device
US11622996B2 (en) 2018-05-07 2023-04-11 Novo Nordisk A/S Solid compositions comprising a GLP-1 agonist and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid
US11718665B2 (en) 2014-05-15 2023-08-08 Rani Therapeutics, Llc Pharmaceutical compositions and methods for fabrication of solid masses comprising polypeptides and/or proteins
US11833248B2 (en) 2018-02-02 2023-12-05 Novo Nordisk A/S Solid compositions comprising a GLP-1 agonist and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2017521479A (ja) 2014-05-15 2017-08-03 ラニ セラピューティクス， エルエルシー ポリペプチドおよび／またはタンパク質を含む固体塊の薬学的組成物およびそれを製造するための方法
JP2018505173A (ja) * 2015-01-29 2018-02-22 ノヴォ ノルディスク アー／エス 錠剤コアと即時放出コーティングとを含む経口ｇｌｐ−１投与用の医薬組成物
LT3280447T (lt) * 2015-04-08 2019-05-27 Torrent Pharmaceuticals Limited Farmacinės kompozicijos

Citations (35)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4525339A (en) 1982-10-15 1985-06-25 Hoffmann-La Roche Inc. Enteric coated oral dosage form
US4722941A (en) 1978-06-07 1988-02-02 Kali-Chemie Pharma Gmbh Readily absorbable pharmaceutical compositions of per se poorly absorbable pharmacologically active agents and preparation thereof
US4772470A (en) 1985-04-27 1988-09-20 Nitto Electric Industrial Co., Ltd. Oral bandage and oral preparations
US5318781A (en) 1993-04-06 1994-06-07 Hoffmann-La Roche Inc. Absorption enhancement of antibiotics
US5393738A (en) 1986-05-27 1995-02-28 Sandoz, Ltd. Pharmaceutical compositions containing octreotide and excipients for oral or rectal administration
US5424289A (en) 1993-07-30 1995-06-13 Alza Corporation Solid formulations of therapeutic proteins for gastrointestinal delivery
US5597562A (en) 1990-06-01 1997-01-28 Kirin-Amgen, Inc. Oral dosage form of biologically active proteins
US5714477A (en) 1993-06-18 1998-02-03 Pharmacia & Upjohn Aktiebolag Pharmaceutical composition containing heparin, heparin fragments or their derivatives in combination with glycerol esters
US5817624A (en) 1995-06-05 1998-10-06 Alza Corporation Permeation enhancer compositions for increased absorption of therapeutic proteins through the colonic membrane
US5827525A (en) 1995-09-12 1998-10-27 Bristol-Myers Squibb Company Buccal delivery system for therapeutic agents
US5827534A (en) 1995-05-24 1998-10-27 University Of Maryland At Baltimore Oral dosage composition comprising zonnula occludens toxin and a therapeutic agent for intestinal delivery
US5854281A (en) 1994-11-17 1998-12-29 Toray Industries, Inc. Preparation for percutaneous absorption
US5912014A (en) 1996-03-15 1999-06-15 Unigene Laboratories, Inc. Oral salmon calcitonin pharmaceutical products
US5929027A (en) 1991-06-07 1999-07-27 Teikoku Seiyaku Kabushiki Kaisha Physiologically active polypeptide-containing pharmaceutical composition
US5952000A (en) 1996-10-30 1999-09-14 Theratech, Inc. Fatty acid esters of lactic acid salts as permeation enhancers
US5972911A (en) 1985-04-02 1999-10-26 Yesair; David W. Composition for the delivery of orally administered drugs and other substances
US6071538A (en) 1992-06-15 2000-06-06 Emisphere Technologies, Inc. Oral delivery composition comprising supramolecular complex
US6156731A (en) 1989-05-10 2000-12-05 G. D. Searle & Co. Polypeptide composition for oral administration
US6200602B1 (en) 1995-08-08 2001-03-13 West Pharmaceutical Services Drug Delivery & Clinical Research Centre Limited Composition for enhanced uptake of polar drugs from the colon
EP1154761A1 (fr) 1999-02-22 2001-11-21 Merrion Research I Limited Dose orale solide contenant un agent de potentialisation
US6333046B1 (en) 1998-03-02 2001-12-25 Hisamitsu Pharmaceutical Co., Inc. Transmucous absorption enhancer
US6423334B1 (en) 1997-10-01 2002-07-23 Elan Corporation, Plc Composition and method for enhancing transport across gastrointestinal tract cell layers
US6747014B2 (en) 1997-07-01 2004-06-08 Isis Pharmaceuticals, Inc. Compositions and methods for non-parenteral delivery of oligonucleotides
WO2005084637A2 (fr) 2004-02-13 2005-09-15 Nod Pharmaceuticals, Inc. Nouveaux procedes et nouvelle composition d'administration de macromolecules par voie orale
US7097851B1 (en) 1998-11-27 2006-08-29 Kanji Takada Oral formulation for gastrointestinal drug delivery
US20070148228A1 (en) 1999-02-22 2007-06-28 Merrion Research I Limited Solid oral dosage form containing an enhancer
US20070196464A1 (en) 1999-02-22 2007-08-23 Merrion Research I Limited Solid oral dosage form containing an enhancer
US7316819B2 (en) 2001-03-08 2008-01-08 Unigene Laboratories, Inc. Oral peptide pharmaceutical dosage form and method of production
US20080275001A1 (en) 1999-02-22 2008-11-06 Merrion Research Iii Limited Solid oral dosage form containing an enhancer
US20080299079A1 (en) 2004-08-25 2008-12-04 Aegis Therapeutics, Llc Absorption Enhancers for Drug Administration
US20090087484A1 (en) 2007-09-28 2009-04-02 Alza Corporation Formulation and dosage form for increasing oral bioavailability of hydrophilic macromolecules
US20090111736A1 (en) 2007-10-29 2009-04-30 Sri International Orally-Absorbed Solid Dose Formulation for Vancomycin
US7576067B2 (en) 2001-08-22 2009-08-18 Isis Pharmaceuticals, Inc. Pulsatile release compositions and methods for enhanced intestinal oligonucleotide drug absorption
US7605123B2 (en) 2004-07-19 2009-10-20 Biocon Ltd. Fatty acid formulations for oral delivery of proteins and peptides, and uses thereof
WO2009135190A2 (fr) 2008-05-01 2009-11-05 Nod Pharmaceuticals, Inc. Particules de phosphate de calcium thérapeutiques et procédés pour les fabriquer et les utiliser

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH0813748B2 (ja) * 1990-04-23 1996-02-14 帝國製薬株式会社 大腸崩壊性ポリペプチド系経口製剤
JPH064531B2 (ja) * 1990-06-04 1994-01-19 アイセロ化学株式会社 大腸崩壊性硬質カプセル
EP0759303B1 (fr) * 1994-04-22 2002-10-16 Yamanouchi Pharmaceutical Co. Ltd. Systeme de liberation de medicament specifique au colon
US5891474A (en) * 1997-01-29 1999-04-06 Poli Industria Chimica, S.P.A. Time-specific controlled release dosage formulations and method of preparing same
US6355270B1 (en) * 1999-01-11 2002-03-12 The Regents Of The University Of California Particles for oral delivery of peptides and proteins
CA2531136A1 (fr) * 2003-07-04 2005-01-13 Nycomed Danmark Aps Compositions pharmaceutiques contenant une hormone parathyroide (pth) administrees par voie orale

Patent Citations (36)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4722941A (en) 1978-06-07 1988-02-02 Kali-Chemie Pharma Gmbh Readily absorbable pharmaceutical compositions of per se poorly absorbable pharmacologically active agents and preparation thereof
US4525339A (en) 1982-10-15 1985-06-25 Hoffmann-La Roche Inc. Enteric coated oral dosage form
US5972911A (en) 1985-04-02 1999-10-26 Yesair; David W. Composition for the delivery of orally administered drugs and other substances
US4772470A (en) 1985-04-27 1988-09-20 Nitto Electric Industrial Co., Ltd. Oral bandage and oral preparations
US5393738A (en) 1986-05-27 1995-02-28 Sandoz, Ltd. Pharmaceutical compositions containing octreotide and excipients for oral or rectal administration
US6156731A (en) 1989-05-10 2000-12-05 G. D. Searle & Co. Polypeptide composition for oral administration
US5597562A (en) 1990-06-01 1997-01-28 Kirin-Amgen, Inc. Oral dosage form of biologically active proteins
US5929027A (en) 1991-06-07 1999-07-27 Teikoku Seiyaku Kabushiki Kaisha Physiologically active polypeptide-containing pharmaceutical composition
US6071538A (en) 1992-06-15 2000-06-06 Emisphere Technologies, Inc. Oral delivery composition comprising supramolecular complex
US5318781A (en) 1993-04-06 1994-06-07 Hoffmann-La Roche Inc. Absorption enhancement of antibiotics
US5714477A (en) 1993-06-18 1998-02-03 Pharmacia & Upjohn Aktiebolag Pharmaceutical composition containing heparin, heparin fragments or their derivatives in combination with glycerol esters
US5424289A (en) 1993-07-30 1995-06-13 Alza Corporation Solid formulations of therapeutic proteins for gastrointestinal delivery
US5854281A (en) 1994-11-17 1998-12-29 Toray Industries, Inc. Preparation for percutaneous absorption
US5827534A (en) 1995-05-24 1998-10-27 University Of Maryland At Baltimore Oral dosage composition comprising zonnula occludens toxin and a therapeutic agent for intestinal delivery
US5817624A (en) 1995-06-05 1998-10-06 Alza Corporation Permeation enhancer compositions for increased absorption of therapeutic proteins through the colonic membrane
US6200602B1 (en) 1995-08-08 2001-03-13 West Pharmaceutical Services Drug Delivery & Clinical Research Centre Limited Composition for enhanced uptake of polar drugs from the colon
US5827525A (en) 1995-09-12 1998-10-27 Bristol-Myers Squibb Company Buccal delivery system for therapeutic agents
US5912014A (en) 1996-03-15 1999-06-15 Unigene Laboratories, Inc. Oral salmon calcitonin pharmaceutical products
US5952000A (en) 1996-10-30 1999-09-14 Theratech, Inc. Fatty acid esters of lactic acid salts as permeation enhancers
US6747014B2 (en) 1997-07-01 2004-06-08 Isis Pharmaceuticals, Inc. Compositions and methods for non-parenteral delivery of oligonucleotides
US6423334B1 (en) 1997-10-01 2002-07-23 Elan Corporation, Plc Composition and method for enhancing transport across gastrointestinal tract cell layers
US6333046B1 (en) 1998-03-02 2001-12-25 Hisamitsu Pharmaceutical Co., Inc. Transmucous absorption enhancer
US7097851B1 (en) 1998-11-27 2006-08-29 Kanji Takada Oral formulation for gastrointestinal drug delivery
US20080275001A1 (en) 1999-02-22 2008-11-06 Merrion Research Iii Limited Solid oral dosage form containing an enhancer
EP1154761A1 (fr) 1999-02-22 2001-11-21 Merrion Research I Limited Dose orale solide contenant un agent de potentialisation
US20070148228A1 (en) 1999-02-22 2007-06-28 Merrion Research I Limited Solid oral dosage form containing an enhancer
US20070196464A1 (en) 1999-02-22 2007-08-23 Merrion Research I Limited Solid oral dosage form containing an enhancer
US7316819B2 (en) 2001-03-08 2008-01-08 Unigene Laboratories, Inc. Oral peptide pharmaceutical dosage form and method of production
US7576067B2 (en) 2001-08-22 2009-08-18 Isis Pharmaceuticals, Inc. Pulsatile release compositions and methods for enhanced intestinal oligonucleotide drug absorption
US20050234114A1 (en) 2004-02-13 2005-10-20 Lee William W Therapeutic calcium phosphate particles and methods of making and using same
WO2005084637A2 (fr) 2004-02-13 2005-09-15 Nod Pharmaceuticals, Inc. Nouveaux procedes et nouvelle composition d'administration de macromolecules par voie orale
US7605123B2 (en) 2004-07-19 2009-10-20 Biocon Ltd. Fatty acid formulations for oral delivery of proteins and peptides, and uses thereof
US20080299079A1 (en) 2004-08-25 2008-12-04 Aegis Therapeutics, Llc Absorption Enhancers for Drug Administration
US20090087484A1 (en) 2007-09-28 2009-04-02 Alza Corporation Formulation and dosage form for increasing oral bioavailability of hydrophilic macromolecules
US20090111736A1 (en) 2007-10-29 2009-04-30 Sri International Orally-Absorbed Solid Dose Formulation for Vancomycin
WO2009135190A2 (fr) 2008-05-01 2009-11-05 Nod Pharmaceuticals, Inc. Particules de phosphate de calcium thérapeutiques et procédés pour les fabriquer et les utiliser

Non-Patent Citations (13)

* Cited by examiner, † Cited by third party
Title
"DEVELOPING SOLID ORAL DOSAGE FORMS: PHARMACEUTICAL THEORY AND PRACTICE", 2009, ACADEMIC PRESS
"FORMULATION AND ANALYTICAL DEVELOPMENT FOR Low DOSE ORAL DRUG PRODUCTS", 2009, WILEY
B.J. AUNGST, J PHARM. SCI., vol. 89, no. 4, 2000, pages 429 - 442
BURCHAM ET AL., PHARM. RES., vol. 12, no. 12, 1995, pages 2065 - 2070
E.K. ANDERBERG ET AL., PHARM. RES., vol. 10, no. 6, 1993, pages 857 - 864
K. WHITEHEAD ET AL., J CONTROL. RELEASE, vol. 98, no. 1, 2004, pages 37 - 45
M. & I. ASH: "THE HANDBOOK OF PHARMACEUTICAL ADDITIVES", 2007, SYNAPSE INFORMATION RESOURCES, INC.
PHARM. RES., vol. 12, no. 12, 1995, pages 2065 - 7200
REMINGTON: "THE SCIENCE AND PRACTICE OF PHARMACY", 2005, LIPPINCOTT WILLIAMS & WILKINS
S. EAIMTRAKARN ET AL., BIOMATERIALS, vol. 23, no. 1, 2002, pages 145 - 152
S. EAIMTRAKARN ET AL., INTL. J PHARM., vol. 250, no. 1, 2003, pages 111 - 117
S.L. TAO; T.A. DESAI, DRUG DISCOV. TODAY, vol. 10, no. 13, 2005, pages 909 - 915
T. LINDMARK ET AL., PHARM. RES., vol. 14, no. 7, 1997, pages 930 - 935

Cited By (31)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2016155811A (ja) * 2010-01-28 2016-09-01 メリオン・リサーチ・Ｉｉｉ・リミテッド 増強剤を含む固形医薬組成物およびその調製方法
US10086047B2 (en) 2010-12-16 2018-10-02 Novo Nordisk A/S Solid compositions comprising a GLP-1 agonist and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid
US11382957B2 (en) 2010-12-16 2022-07-12 Novo Nordisk A/S Solid compositions comprising a GLP-1 agonist and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid
US10960052B2 (en) 2010-12-16 2021-03-30 Novo Nordisk A/S Solid compositions comprising a GLP-1 agonist and a salt of N-(8-(2-hydroxybenzoyl) amino) caprylic acid
US9278123B2 (en) 2010-12-16 2016-03-08 Novo Nordisk A/S Solid compositions comprising a GLP-1 agonist and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid
US11117947B2 (en) 2011-04-12 2021-09-14 Novo Nordisk A/S Double-acylated GLP-1 derivatives
US11034746B2 (en) 2011-04-12 2021-06-15 Novo Nordisk A/S Double-acylated GLP-1 derivatives
JP2014520889A (ja) * 2011-07-19 2014-08-25 バクスター・インターナショナル・インコーポレイテッド 非抗凝固性硫酸化多糖の経口製剤を改善するための添加剤としての吸収促進剤
US10335369B2 (en) 2012-03-22 2019-07-02 Novo Nordisk A/S Compositions comprising a delivery agent and preparation thereof
US11123296B2 (en) 2012-03-22 2021-09-21 Novo Nordisk A/S Compositions comprising a delivery agent and preparation thereof
US11759502B2 (en) 2012-03-22 2023-09-19 Novo Nordisk A/S Compositions of GLP-1 peptides and preparation thereof
US11759503B2 (en) 2012-03-22 2023-09-19 Novo Nordisk A/S Compositions of GLP-1 peptides and preparation thereof
US11759501B2 (en) 2012-03-22 2023-09-19 Novo Nordisk A/S Compositions of GLP-1 peptides and preparation thereof
US10933120B2 (en) 2012-03-22 2021-03-02 Novo Nordisk A/S Compositions of GLP-1 peptides and preparation thereof
US9993430B2 (en) 2012-06-20 2018-06-12 Novo Nordisk A/S Tablet formulation comprising semaglutide and a delivery agent
US11033499B2 (en) 2012-06-20 2021-06-15 Novo Nordisk A/S Tablet formulation comprising a GLP-1 peptide and a delivery agent
WO2015010927A1 (fr) * 2013-07-24 2015-01-29 Novo Nordisk A/S Composition pharmaceutique pour administration orale d'insuline comprenant un cœur de comprimé et un enrobage de copolymère anionique
EP3121195A4 (fr) * 2014-03-21 2017-10-11 Anygen Co., Ltd. Nouvel analogue de l'exénatide et son utilisation
US11103557B2 (en) 2014-03-21 2021-08-31 Anygen Co., Ltd. Exenatide analogue and use thereof
US11718665B2 (en) 2014-05-15 2023-08-08 Rani Therapeutics, Llc Pharmaceutical compositions and methods for fabrication of solid masses comprising polypeptides and/or proteins
US11548940B2 (en) 2014-05-15 2023-01-10 Rani Therapeutics, Llc Anti-interleukin antibody preparations for delivery into a lumen of the intestinal tract using a swallowable drug delivery device
WO2016119854A1 (fr) * 2015-01-29 2016-08-04 Novo Nordisk A/S Composition pharmaceutique pour l'administration d'insuline par voie orale comprenant un noyau de comprimé et un enrobage d'alcool polyvinylique
US10265384B2 (en) 2015-01-29 2019-04-23 Novo Nordisk A/S Tablets comprising GLP-1 agonist and enteric coating
US20180000742A1 (en) * 2015-01-29 2018-01-04 Novo Nordisk A/S Pharmaceutical Composition for Oral Insulin Administration Comprising a Tablet Core and a Polyvinyl Alcohol Coating
EP3250191B1 (fr) * 2015-01-29 2024-01-17 Novo Nordisk A/S Comprimés contenant un agoniste de glp-1 et revêtement gastro-résistant
CN104998251A (zh) * 2015-07-08 2015-10-28 哈尔滨吉象隆生物技术有限公司 用于口服肠溶制剂制备的具有促肠吸收作用的利拉鲁肽盐
CN105079793A (zh) * 2015-07-18 2015-11-25 哈尔滨吉象隆生物技术有限公司 一种可用于口服的利拉鲁肽与盐酸二甲双胍复方制剂
CN105079794A (zh) * 2015-07-18 2015-11-25 哈尔滨吉象隆生物技术有限公司 一种可用于口服的利拉鲁肽与磺脲类复方制剂
RU2617049C1 (ru) * 2016-05-12 2017-04-19 Федеральное государственное бюджетное учреждение "Национальный исследовательский центр "Курчатовский институт" Противоопухолевое лекарственное средство на основе никлозамида
US11833248B2 (en) 2018-02-02 2023-12-05 Novo Nordisk A/S Solid compositions comprising a GLP-1 agonist and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid
US11622996B2 (en) 2018-05-07 2023-04-11 Novo Nordisk A/S Solid compositions comprising a GLP-1 agonist and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid

Also Published As

Publication number Publication date
WO2011084618A3 (fr) 2012-01-19
AU2010339907A1 (en) 2012-07-05
JP2013514976A (ja) 2013-05-02
CA2784120A1 (fr) 2011-07-14
EP2512454A2 (fr) 2012-10-24

Similar Documents

Publication Publication Date Title
US20110142889A1 (en) Compositions and methods for oral drug delivery
WO2011084618A2 (fr) Compositions et procédés d'administration de médicaments par voie orale
EP0932396B1 (fr) Forme posologique pharmaceutique comportant plusieurs enrobages polymeres enteriques, destinee a agir dans le colon
US20180098934A1 (en) Mucoadhesive devices for delivery of active agents
US20230073256A1 (en) Oral delivery of active drug substances
ES2301477T3 (es) Forma de dosificacion oral solida que contiene un potenciador.
CA2642479C (fr) Systeme de gastro-retention pour de livrer des macromolecules
EP2526950A1 (fr) Forme pharmaceutique solide par voie orale contenant un activateur
CN102552919B (zh) 一种给药组合物及其制备和使用方法
CN102100912B (zh) 一种给药组合物及其制备和使用方法
US20110250238A1 (en) System for the colon delivery of drugs subject to enzyme degradation and/or poorly absorbed in the gastrointestinal tract
CN102335431B (zh) 一种给药组合物及其制备和使用方法
WO2015026552A2 (fr) Dispositifs mucoadhésifs permettant l'administration d'agents actifs
CN110974943A (zh) 一种口服胰岛素药物制剂及其制备方法
US20230000779A1 (en) Room temperature stable oral calcitonin formulation
WO2023166224A1 (fr) Formulations gastro-rétentives contenant une protéine ou un peptide
CN110809464A (zh) 粘膜附着性口服制剂

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 10795591

Country of ref document: EP

Kind code of ref document: A1

ENP Entry into the national phase

Ref document number: 2784120

Country of ref document: CA

WWE Wipo information: entry into national phase

Ref document number: 2010795591

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: 2012544835

Country of ref document: JP

Ref document number: 2010339907

Country of ref document: AU

NENP Non-entry into the national phase

Ref country code: DE

ENP Entry into the national phase

Ref document number: 2010339907

Country of ref document: AU

Date of ref document: 20101216

Kind code of ref document: A

WWE Wipo information: entry into national phase

Ref document number: 1728/KOLNP/2012

Country of ref document: IN