[go: up one dir, main page]

WO2008154240A1 - Composition pharmaceutique d'un nouveau système destiné à la libération de stéroïdes dans le vagin - Google Patents

Composition pharmaceutique d'un nouveau système destiné à la libération de stéroïdes dans le vagin Download PDF

Info

Publication number
WO2008154240A1
WO2008154240A1 PCT/US2008/065722 US2008065722W WO2008154240A1 WO 2008154240 A1 WO2008154240 A1 WO 2008154240A1 US 2008065722 W US2008065722 W US 2008065722W WO 2008154240 A1 WO2008154240 A1 WO 2008154240A1
Authority
WO
WIPO (PCT)
Prior art keywords
composition
fact
per
vaginal
weight
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.)
Ceased
Application number
PCT/US2008/065722
Other languages
English (en)
Inventor
Ariel Fuentes
Luigi Devoto
Ricardo Pomer
Hugo Sovino
Pablo CÉSPEDES
Leon Trejo
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.)
Universidad de Chile
Biohealth LLC
Original Assignee
Universidad de Chile
Biohealth LLC
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 Universidad de Chile, Biohealth LLC filed Critical Universidad de Chile
Priority to MX2009013305A priority Critical patent/MX2009013305A/es
Priority to EP08770092A priority patent/EP2157946A1/fr
Priority to CA2689987A priority patent/CA2689987A1/fr
Priority to CN200880019113A priority patent/CN101730514A/zh
Priority to BRPI0812578A priority patent/BRPI0812578A2/pt
Publication of WO2008154240A1 publication Critical patent/WO2008154240A1/fr
Anticipated expiration legal-status Critical
Ceased 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
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0034—Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
    • 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
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, 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
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • 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
    • A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
    • 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

Definitions

  • the current invention includes a solid pharmaceutical form, containing only progesterone, or progesterone combined with estradiol, to be administered vaginally. It is a proven fact nowadays that the effector reproductive organs (hypophysis-ovary and uterus) receive impulses rather of permissive than controlling type from the hormones addressed to them (de Ziegler, 1995). On the other hand, another even more unexpected phenomenon has been recently disclosed regarding hormones and their effect when vaginally administered. A high efficiency at the endometrium tissue level has become evident, as well as a low progesterone plasmatic concentration achieved with this administration means (Miles et al, 1994; Fanchin et al, 1997).
  • injectable means in prolonged therapies is uncomfortable and not free of side effects, such as pain and complications, like a cold abscess.
  • Vaginal means have been considered one of the alternatives since ancient times. Recently we have witnessed a revival of this drug administration means, since the development of new release systems has resulted into excellent pharmacokinetic profiles, with minimum side effects.
  • the term 'first uterine step' has been used in the literature to describe a phenomenon by which a drug reaches higher concentration levels in the pelvic organs than in peripheral circulation (Bulletti et al;1997), (Einer-Jensen et al, 2001 ).
  • the local venous-arterial transfer of solutes is required by means of the so-called vascular counter-flow mechanism, the existence of which has been widely proven in the literature (Cicinelly et al, 1998; Alexander et al, 2004)
  • the vagina has a self-cleaning system, which added to the gravity law opposes to the retention of a drug inside the vaginal means.
  • muco-adherence is a fundamental feature for a drug release system at a vaginal level.
  • Polymers allow the drugs to stay inside the vagina and being released at a constant speed towards the vaginal means, determining a 'concentration gradient' between vaginal lumen and the wide network of underlying veins and venous capillaries (Bernkop et al, 2004), (Gavini E. et al, 2002).
  • the last concept is fundamental for molecules capable of achieving trans-membrane passive diffusion (Vermani and Garg, 2000). Such diffusion in the vaginal means is favored in lipophilic molecules of low molecular weight (about 300 Daltons), (Niswender,2002).
  • Natural progesterone and estradiol possess such requirements, and their main clinical uses are related to the support of the luteal phase in assisted fertilization cycles, where analogues of the gonadotropin (GnRH) releasing hormone have been used.
  • GnRH gonadotropin
  • progestagen is a controverted matter in the 'post WHI era' (Women ' s Health Initiative) and its association to breast cancer is also doubtful. Nevertheless, a recent study of two random clinical essays in Sweden showed that, after experiencing breast cancer, the recurrence does not show an increase trend with the cyclic use of a progestagen for 10 days every three months, while the essay that used a continuous combined therapy was interrupted when a significant increase of breast cancer became evident (von Schultz et al, 2005).
  • Vaginal administration of progesterone could then mean achieving a significant effect of the steroid on the effector organs (myometrium and endometrium), with little consequences at a systemic circulation level, avoiding distance effects (Norman and Mac Lennan; 2005). Both the luteal phase support, as well as the hormone replacement therapy, require a prolonged use of progesterone.
  • vaginal means has been traditionally used in the release of drugs that act locally, as anti-microbe and anti-parasite agents. Nevertheless, conventional systems such as creams, foams, pessaries and jellies remain for relatively short terms at their destination site due to the self-cleaning system of the vaginal tract. Consequently, effective therapeutic levels of a drug are limited to a short term, thus requiring a repeated administration through time. A good drug release system must provide controlled and sustained levels of the administered drug.
  • mucous adhesive polymers Many drug release systems are based on mucous adhesive polymers (Lee et al, 2000).
  • the mucous adhesive systems of drug release have been developed both for local and systemic administration through different mucous: oral (Giunchedi et al, 2002), nasal (Lim et al, 2000) and vaginal (Valenta et al, 2001 ), (Lee et al, 1996).
  • Chitosane is one of them (Luessen et al, 1997), which in general shows some advantages over low molecular weight polymers, such as the increase of mucous adhesive features, thus allowing high concentrations of them to remain at the absorbance site (Uchiyama et al, 1999).
  • Chitosane is a polysaccharide obtained from partial chitin de-acetylation (Muzzarelli et al, 1988). Due to its great bio-compatibility and bio-degrading, it is widely used as pharmaceutical excipient.
  • Chitosane also shows anti-microbe and cicatrizing properties (Conti et al, 2000), (Kan et al, 2000).
  • the use of chitosane as a mucous adhesive polymer in humans via oral means has already been studied (Giunchedi et al, 2002). Nevertheless, vaginal means for this purpose has not been explored.
  • polymers can be divided into anionic and cationic, being chitosane one of the most used cationic polymers.
  • Carbomer is a polymer of the acrylic acid that shows a crossed reaction with poly alkenyl glycol or divinyl glycol ethers. They are produced from polymer primary particles of about 0.2 to 6 microns average diameter. Floculated agglomerates cannot be divided in the last particles when synthesized. Each particle may be seen as a structural network of the polymer interconnected with others.
  • Carbomer which was discovered and patented in 1957, is also known as Carbomer, Carboxipolymethylene and its commercial name, Carbopol®. Since then a wide range of formulations in oral tablets has been patented. Carbomer has a great affinity with water, under which contact it swallows and hydrates. Besides its hydrophilic nature, its inter-crossed structure is essentially insoluble in water. Consequently, it is a potential candidate for its use in drug controlled release systems.
  • Carboxile groups provided with acrylic acid, are responsible for many benefits of the product.
  • Carbomer polymers have a weight equivalent to 76 per carboxile group, and are manufactured with an inter-crossing process. Depending from the intercrossing degree and the manufacturing conditions, there are several carbomer degrees available. Each degree has a different meaning, depending on its use for pharmaceutical preparations.
  • Carbomer 974 is inter-crossed with erythritol penta allyl and polymerized in ethyl acetate. All polymers manufactured this way are neutralized by a 1 % and a 3% potassium hydroxide. The tri-dimensional nature of this polymer provides it with some unique features, such as being biologically inert.
  • Carbomer is a hydrophylic substance not soluble in water: instead of dissolving in the presence of water, carbomer swallows, forming a mucilaginous colloid.
  • Carbomer polymers have a remarkable water absorbance feature, they swallow in the presence of water until reaching over 1 ,000 times their original volume, and 10 times their diameter until forming a gel, when exposed to a pH between 4 and 6.
  • the current invention decreases such index, both in-vitro as well as in-vivo, preventing the accumulation of residues in the vaginal cavity.
  • the appropriate weighing weight- weight ratio of polymers and of the rest of the excipients allows a higher spacing in- between the doses to be administered.
  • carbopol showed the best results in terms of active principle release and showed excellent mucous adhesive properties in the in vitro mucous adherence essays.
  • Preliminary studies carried out by us showed that this polymers combination, used under the same conditions, can be used in the women's vagina, without any significant collateral effect.
  • vaginal release of gonadotropins LH and FSH was tried, with in vitro fertilization purposes.
  • gonadotropins LH and FSH
  • Such peptide hormones have an extraordinarily high molecular weight as compared to progesterone ( ⁇ 30.000 vs. 300 Daltons). The results showed a modest vaginal absorbance of gonadotropins, not compatible with its clinical use.
  • progesterone administration through this new release system made of a polymers mixture with well defined ratios, formulated with a disintegrating agent which is formed, in turn, by the combination of at least two of the following agents: Sodium glycolate starch, microcrystalline cellulose, crospovidone or sodium croscarmellose, a diluent and a mixture of lubricants, where at least one of them has a weight between 0.05% and 3.5%, leads to good results, decreasing the disintegration /dissolution index, preventing the residues accumulation in the vaginal cavity.
  • a disintegrating agent which is formed, in turn, by the combination of at least two of the following agents: Sodium glycolate starch, microcrystalline cellulose, crospovidone or sodium croscarmellose, a diluent and a mixture of lubricants, where at least one of them has a weight between 0.05% and 3.5%
  • Progesterone was associated to this new vaginal release system of drugs in replacement of synthetic progestagens, as a hormone replacement therapy during post menopause.
  • the new release system contains chitosane, a polymer extremely abundant in the nature, which is part of the shell of several crustaceans. Chitosane is incorporated to pharmaceutical forms as a powder that, in contact with water, becomes a gel which molecular array that offers the features of a framework.
  • chitosane is not limited only to the product obtained by chitin de-acetylation, but it also includes any chitosane dehvate that has been modified with the purpose of improving its biocompatibility, biodegrading or solubility, as several dehvates known in the state of the technique, such as: partially hydrolyzed chitosane, partially re- acetyled chitosane, etc.
  • the vaginal tablet also contains a carbomer, a synthetic polymer with a high mucous adhesive power, also known as carboxypolymethylene.
  • carbomer a synthetic polymer with a high mucous adhesive power
  • carboxypolymethylene a synthetic polymer with a high mucous adhesive power
  • vaginal tablets may be prepared with granulation and compression, and dried with 'spray-drying' or liophylization, among others.
  • Mucous adhesive properties are developed when the tablet is hydrated by the vaginal physiological fluids.
  • Pharmacokinetic parameters were determined for progesterone, such as maximum concentration, maximum time, elimination mean life, so as to ensure a local, non systemic action. For this purpose a frequent blood sampling was necessary during the first 24 hours after the administration, and then daily until the fourth day.
  • composition is characterized by the fact of containing Progesterone, or Progesterone/Estradiol and excipients pharmaceutically acceptable, such as: polymers, a diluter, a disintegrating agent, a glydant and a mixture of lubricants.
  • compositions described are the fact of possessing mucous adhesive type excipients, which allows the active principle to remain in the vaginal mucous for a longer time.
  • the American patent application US 2004/0132690 refers to a pharmaceutical composition for vaginosis treatment, of vaginal administration, which includes a gel based on chitosane and lactic acid.
  • the American patent US 7,018,992 describes a pharmaceutical composition containing estradiol for the treatment of vaginal atrophy. This composition includes a matrix with a hydrophilic cellulose film coat, which adheres to the vaginal mucous and hydrates slowly to provide a controlled release of estradiol.
  • Vaginal tablets containing progesterone have been described in the literature, but they must be administered twice a day (Levy et col, 1999), as well as tablets containing Clotrimazole and a combination of bio-adhesive polymers such as:
  • Carbomer 934P sodium carboxymethylcellulose and sodium alginate, to be administered once a day. (Sharma, G. et col, 2006).
  • the current invention provides a tablet for vaginal administration of micronized progesterone for non systemic use which includes the steps of: a) Mixing the micronized progesterone with other pharmaceutically acceptable excipients. b) Forming a tablet by the traditional compressing system with the micronized progesterone, which has been mixed with other pharmaceutically acceptable excipients, such as: mucous adhesive excipients, diluters, a disintegrating agent, a glydant and a mixture of lubricants.
  • micronized progesterone and estradiol must have a particle size between
  • micronized progesterone must be in a weight ratio between 1 : 2 to 1 : 6, regarding the mixture of mucous adhesive polymers.
  • mucous adhesive polymers must be chitosane and carbomer 974P, in a weight ratio of 1 : 3 to 1 : 5 in between them.
  • the diluter must be one of the following agents: Lactose, Lactose monohydrate, Lactose Spray dried, calcium di-basic Phosphate, Sucrose, Mannitol or cellulose, with a weight between 0.05% and 50.0% of the tablet total weight.
  • the disintegrating agent must be formed by the mixture of, at least, two of the following: Sodium glycolate starch, microcrystalline cellulose, crospovidone and sodium croscarmellose, with a weight between 0.02% and 30.0% of the tablet total weight for each of the agents.
  • a glydant agent such as colloidal silicon
  • a weight between 0.01 % and 5.0% of the tablet total weight.
  • the lubricants mixture must be talcum and magnesium stearate, and at least one of them with a weight between 0.05% and 3.5% of the tablet total weight.
  • compositions indicated in this patent are an example and they do not limit the scope and protection of the invention.
  • Drugs disintegration depends on the diluter used, the kind and quantity of agglutinating, and mainly the disintegrating agent, the lubricant quantity, the compacting pressure and the incorporation method. If a tablet disintegrates, it does not mean that the drug dissolves: the disintegration time was established with the pharmacopeia equipment and criteria, using distilled water as a means, table 2; Dissolution ( 71 1 ), page 2303, as the disintegration test does not guarantee that the formulation releases the drug, the dissolution test is carried out, since tablets must dissolve before absorbance or act in the site of action.
  • the absorbance speed of a drug is determined by the dissolution speed of the tablets; the dissolution kinetics for each of the formulations was carried out considering the equipment and criteria of pharmacopeia, using purified water at 37 a C as a means, 50 rpm and the method II, Table 2 and graphs 1 , 2 and 3.
  • Plasma concentrations of progesterone are higher in the uterine artery than in the radial artery after vaginal administration of micronized progesterone in an oil based solution to postmenopausal women. Fertil. Steril., 69, 471-473.

Landscapes

  • Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Endocrinology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Diabetes (AREA)
  • Gynecology & Obstetrics (AREA)
  • Reproductive Health (AREA)
  • Urology & Nephrology (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne des compositions pharmaceutiques appropriées à une administration de stéroïdes par voie vaginale. Lesdites compositions sont destinées à être utilisées dans une hormonothérapie substitutive, durant la ménopause, et à soutenir la phase lutéale des cycles de fécondation in vitro. Ces compositions se caractérisent par l'incorporation de polymères et de combinaisons de délitants, ce qui permet une adhérence adéquate aux muqueuses ainsi que la biodisponibilité des hormones stéroïdes dans l'endomètre. Ce procédé d'administration réduit les niveaux systémiques des stéroïdes, permet d'allonger la période séparant les doses - ce qui diminue les effets secondaires -, et empêche le regroupement des résidus dans la cavité vaginale.
PCT/US2008/065722 2007-06-06 2008-06-04 Composition pharmaceutique d'un nouveau système destiné à la libération de stéroïdes dans le vagin Ceased WO2008154240A1 (fr)

Priority Applications (5)

Application Number Priority Date Filing Date Title
MX2009013305A MX2009013305A (es) 2007-06-06 2008-06-04 Composicion farmaceutica de un nuevo sistema para liberacion vaginal de esteroides.
EP08770092A EP2157946A1 (fr) 2007-06-06 2008-06-04 Composition pharmaceutique d'un nouveau système destiné à la libération de stéroïdes dans le vagin
CA2689987A CA2689987A1 (fr) 2007-06-06 2008-06-04 Composition pharmaceutique d'un nouveau systeme destine a la liberation de steroides dans le vagin
CN200880019113A CN101730514A (zh) 2007-06-06 2008-06-04 用于类固醇阴道释放的新体系的药物组合物
BRPI0812578A BRPI0812578A2 (pt) 2007-06-06 2008-06-04 composição farmacêutica de um novo sistema para liberação vaginal de esteróides

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CL1634-2007 2007-06-06
CL2007001634 2007-06-06

Publications (1)

Publication Number Publication Date
WO2008154240A1 true WO2008154240A1 (fr) 2008-12-18

Family

ID=40951496

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2008/065722 Ceased WO2008154240A1 (fr) 2007-06-06 2008-06-04 Composition pharmaceutique d'un nouveau système destiné à la libération de stéroïdes dans le vagin

Country Status (9)

Country Link
EP (1) EP2157946A1 (fr)
CN (1) CN101730514A (fr)
AR (1) AR070302A1 (fr)
BR (1) BRPI0812578A2 (fr)
CA (1) CA2689987A1 (fr)
CO (1) CO6270199A2 (fr)
MX (1) MX2009013305A (fr)
PE (1) PE20090324A1 (fr)
WO (1) WO2008154240A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011073995A2 (fr) 2009-12-14 2011-06-23 Lincoln Pharmaceuticals Limited Liquide contenant de la progestérone à pulvériser dans le vagin
WO2015073066A1 (fr) 2013-11-12 2015-05-21 University Of Utah Research Foundation Hydrogel thermosensible à base de glycol-chitine pour administration de progestérone par voie vaginale

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114129530A (zh) * 2021-12-08 2022-03-04 南京康川济医药科技有限公司 一种黄体酮缓释组合物及其制备方法

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997040792A1 (fr) * 1996-04-30 1997-11-06 Theratech, Inc. Administration transdermique d'hormones steroidiennes au moyen de diethanolamides d'acides gras c12-c18 utilises comme activateurs de l'infiltration
US20040132690A1 (en) * 2001-05-04 2004-07-08 Carmella Carla Marcella Compositions with controlled release of lactic acid at vaginal level

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997040792A1 (fr) * 1996-04-30 1997-11-06 Theratech, Inc. Administration transdermique d'hormones steroidiennes au moyen de diethanolamides d'acides gras c12-c18 utilises comme activateurs de l'infiltration
US20040132690A1 (en) * 2001-05-04 2004-07-08 Carmella Carla Marcella Compositions with controlled release of lactic acid at vaginal level

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011073995A2 (fr) 2009-12-14 2011-06-23 Lincoln Pharmaceuticals Limited Liquide contenant de la progestérone à pulvériser dans le vagin
WO2011073995A3 (fr) * 2009-12-14 2011-08-11 Lincoln Pharmaceuticals Limited Liquide contenant de la progestérone à pulvériser dans le vagin
WO2015073066A1 (fr) 2013-11-12 2015-05-21 University Of Utah Research Foundation Hydrogel thermosensible à base de glycol-chitine pour administration de progestérone par voie vaginale
EP3068223A4 (fr) * 2013-11-12 2017-06-21 University of Utah Research Foundation Hydrogel thermosensible à base de glycol-chitine pour administration de progestérone par voie vaginale

Also Published As

Publication number Publication date
CA2689987A1 (fr) 2008-12-18
PE20090324A1 (es) 2009-04-09
BRPI0812578A2 (pt) 2015-09-29
CO6270199A2 (es) 2011-04-20
AR070302A1 (es) 2010-03-31
EP2157946A1 (fr) 2010-03-03
CN101730514A (zh) 2010-06-09
MX2009013305A (es) 2010-04-21

Similar Documents

Publication Publication Date Title
Valenta The use of mucoadhesive polymers in vaginal delivery
Sahoo et al. Intra vaginal drug delivery system: an overview
Brannon-Peppas Novel vaginal drug release applications
US11026883B2 (en) Lyophilized pharmaceutical compositions for vaginal delivery
MXPA04006017A (es) Suministro de farmacos por via vaginal.
JP2007506797A (ja) 向上した安定性のプロゲストーゲン製剤
HU227198B1 (en) Pharmaceutical composition for emergency contraception containing levonorgestrel
Gupta et al. Exploring novel approaches to vaginal drug delivery
EP2210585A1 (fr) Compositions pharmaceutiques SPRM et procédés de traitement les utilisant
WO2008154240A1 (fr) Composition pharmaceutique d'un nouveau système destiné à la libération de stéroïdes dans le vagin
CN102000339A (zh) 缓释释药的药物载体
Gupta et al. Intravaginal delivery approaches for contraception: an overview with emphasis on gels
US20050070501A1 (en) Water dispersible film
Borges et al. Drug delivery systems for vaginal infections
Hani et al. Novel vaginal drug delivery systems: a review
US20220331337A1 (en) Orodispersible formulations
Krishna et al. A review on vaginal drug delivery systems
US12370203B2 (en) Pharmaceutical compositions and methods of making on demand solid dosage formulations
US10172869B2 (en) Progesterone receptor modulators for use in the therapy of uterine fibroids
Gu et al. Drug delivery: intravaginal, advantages and challenges
US20240115490A1 (en) Drug delivery system for ultra-low dose estrogen combinations and methods and uses thereof
Nayak et al. Novel approaches in vaginal drug delivery systems for local and systemic treatments
CN100430032C (zh) 水分散膜剂
Tong ASSESSMENT OF THE PROGESTIN POLYMERIC VAGINAL FILMS BY AN OPTIMIZED SOLVENT-CAST PLATFORM
Sathapathy Development and Evaluation of Dienogest Vaginal Tablet for Treatment of Endometriosis

Legal Events

Date Code Title Description
WWE Wipo information: entry into national phase

Ref document number: 200880019113.9

Country of ref document: CN

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

Ref document number: 08770092

Country of ref document: EP

Kind code of ref document: A1

WWE Wipo information: entry into national phase

Ref document number: 2689987

Country of ref document: CA

WWE Wipo information: entry into national phase

Ref document number: MX/A/2009/013305

Country of ref document: MX

NENP Non-entry into the national phase

Ref country code: DE

WWE Wipo information: entry into national phase

Ref document number: 2008770092

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: 10001028

Country of ref document: CO

ENP Entry into the national phase

Ref document number: PI0812578

Country of ref document: BR

Kind code of ref document: A2

Effective date: 20091204