US20080317850A1 - Buccal Delivery System - Google Patents

Buccal Delivery System Download PDF

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US20080317850A1
US20080317850A1 US11/910,902 US91090206A US2008317850A1 US 20080317850 A1 US20080317850 A1 US 20080317850A1 US 91090206 A US91090206 A US 91090206A US 2008317850 A1 US2008317850 A1 US 2008317850A1
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delivery system
buccal delivery
agents
matrix
buccal
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Ernest Alan Hewitt
Richard James Stenlake
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OzPharma Pty Ltd
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    • 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
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
    • 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
    • A61K9/2031—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
    • 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
    • A61K9/2095—Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/02—Nutrients, e.g. vitamins, minerals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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
    • A61P5/26—Androgens
    • 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
    • A61P5/30—Oestrogens
    • 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
    • A61P5/34—Gestagens
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system

Definitions

  • the invention relates to a buccal delivery system which provides improved delivery of therapeutic agents.
  • the present invention relates to buccal dosage formulations.
  • the present invention further provides easier and more economic methods of manufacturing a dosage formulation capable of delivering one or more active ingredients via buccal membranes.
  • the formulation itself is often critical to the efficacy of the drug to be delivered. This is particularly the case for the delivery of pain relief agents such as paracetamol.
  • pain relief agents such as paracetamol.
  • One of the rate limiting steps in paracetamol delivery to the blood stream is the rate of gastric emptying.
  • Various formulations which provide paracetamol at an alkaline pH have been proposed.
  • Troches first appeared in the Edinburgh Pharmacopoeia in 1841 and then in 1864 in the British Pharmacopoeia. In the 1800s, troche making was an art way and required a lot of practical experience.
  • the apparatus required to make troches was a smooth marble slab to mix them, a rolling pin, troche cutters, a palette knife, a badger brush with long soft hairs, linen cloth, and troche trays.
  • the computer has replaced the marble slabs, the wooden trays and brushes, etc. with complex electronic mixers, poly-glycol flavoured bases, accurate electronic scales (capable of measuring milligram doses) and miniature electric hot plates that make the finished troche an accurate and precise dosage form.
  • the finished troches are dispensed in plastic calibrated moulds.
  • the troches are available in a wide variety of flavours to assist compliance by even the fussiest patient.
  • the troches provide a means to deliver custom made medication in small doses directly into the blood stream.
  • Troches are currently used in hormone replacement therapy mainly because of the ease in which ingredients in each prescription can be altered and the buccal absorption does not involve gastric metabolism. Troches can also be mixed so that each individual troche contains a combination of various natural hormones in small doses.
  • a troche can be made containing a mixture of any of the bio-identical natural hormones, eg: estrogen, progesterone, testosterone and DHEA in any possible dosage. This combination is used to treat the symptoms of menopause.
  • a combination of testosterone and DHEA is most commonly used.
  • Troches containing natural progesterone alone are helpful for premenstrual syndrome and can be taken during the latter half of the menstrual cycle to alleviate depression, migraine, nausea and basically all those PMT symptoms that occur in the premenstrum.
  • Troches are being marketed as a method of administering agents that bypass the stomach and first pass metabolism of the liver as they are supposedly absorbed directly into buccal circulation. Claims are made that this places less stress on the liver and therefore is better for the patient. In reality, more than 50% (up to 70%) of the troche dose is actually swallowed by the normal salivation process which will encounter the stomach acids and first pass metabolism while the remainder is absorbed by the buccal mucosa ( Int J Pharm Comp., 4, 414-420, 2000). With only 30 to 50% of the dose being absorbed through the mucosal lining in the mouth there appears to be only a minimal reduction in the livers first pass metabolism when compared to capsules.
  • Troches also exhibit poor pharmacokinetic parameters. This means that there are great fluctuations in hormone serum levels after taking a troche dose. Soon after taking a troche serum hormone levels rise rapidly, sometimes to very high levels, and then rapidly fall to low levels within 4 to 5 hours. They therefore require at least twice daily administration or for optimal results three to four times a day to maintain adequate levels longer however compliance becomes a major problem with this type of dosing schedule. This wide fluctuation in hormone levels is not the ideal situation. Creams and slow release capsules release hormones into the blood stream more gradually achieving steadier serum levels for a longer period of time thus generally requiring only once a day dosing.
  • Troches are made from two different types of bases both of which have several drawbacks:
  • Transdermal creams are considered the first choice by many as they require lower doses compared to troches and capsules and they are the only route of administration that truly bypasses the stomach and first pass metabolism. They provide better release parameters providing steady serum levels without wild fluctuations seen with troches. They only require once daily dosing so are more convenient, dosage adjustments are very easy to make and finally they are significantly cheaper with a standard formula costing about $30/month. If creams are deemed unsuitable in certain cases then the second choice should be slow release capsules. These capsules provide better release properties than troches, only require once a day dosing, and are fast to administer and no bitter taste. Troches are thought to be suitable for patients where creams are unsuitable and malabsorption syndrome occurs thus making oral administration unsuitable.
  • One group of drugs which is particularly beneficial in a range of conditions are the bisphosphonates. Osteoporosis is one condition for which the bisphosphonate drugs, alendronate and risedronate, are frequently prescribed.
  • Osteoporosis and selected bone-resorptive conditions represent a significant medical disorder affecting millions of sufferers worldwide.
  • Other bone-resorptive conditions include other diseases or physiological states where there is an actual reduction or risk of reduction in bone mineral density and osteolysis from a normal reference range as a consequence of the disease or physiological state, such as menopause, hypogonadism, osteogenesis imperfecta, Paget's disease, myeloma bone disease, cancers metastatic to bone, primary hyperparathyroidism, fibrous dysplasia and hypercalcemia of malignancy.
  • Sufferers of osteoporosis face long-term drug therapy with anti-resorptive agents to prevent further bone loss.
  • alendronate and risedronate are generally prescribed as anti-resorptive agents.
  • Bisphosphonates are also often prescribed in conjunction with hormone replacement therapy (HRT) to counter the effects of declining sex hormone production around the time of menopause.
  • Sex hormone supplementation generally employs the gastrointestinal administration route, where significant amounts of hormone are degraded by the digestive environments encountered prior to absorption. As such, larger than required amounts of hormones must be used in the manufacture of oral hormone dosage forms to ensure a therapeutic dose reaches the circulation.
  • HRT regimens specific for female menopausal symptoms have been devised, which have met with varying rates of clinical success.
  • the majority of these treatments are based on the use of natural 17- ⁇ -oestradiol, conjugated equine oestrogen, or other conjugated oestrogens in combination with synthesised progestogens such as nor-ethisterone, levonorgestrel and dydrogesterone.
  • progestogens such as nor-ethisterone, levonorgestrel and dydrogesterone.
  • the present invention provides a buccal delivery system which provides improved bioavailability of active agents.
  • the buccal delivery system of the present invention is able to deliver up to and sometimes more than 85% of the active ingredient as it circumvents the action of the liver in ‘first past metabolism’.
  • the term “buccal” is used in its broadest sense to refer to the mouth as a whole and includes sublingual.
  • the buccal delivery system of the present invention provides improved bioavailability, it is possible using the present invention to use less of the active ingredient in the manufacture of dosage forms.
  • the buccal delivery system of the present invention may reduce the severity of gastrointestinal side-effects of particular agents such as indigestion, pain, nausea, vomiting, constipation, cramps, diarrhoea and flatulence.
  • the present invention also provides a buccal delivery system which can be manufactured more easily and more economically as it can be made using a dry manufacturing process with all actives blended in a normal dry powder process and compressed using a standard tabletting machine.
  • Such dry formulations can be manufactured in commercial numbers and provided in conventional blister packaging.
  • the active ingredients and excipients are similar to those used in the prior art troche, however the excipients are modified so that there is no need to use the special wet formulating plant and equipment and manual processing required for the troches (soft gel products) of the prior art which are costly and time intensive.
  • a buccal delivery system capable of being blended in a normal dry powder process and compressed using a standard tabletting machine, said buccal delivery system comprising a matrix of:
  • the effective amount of the active ingredient is typically an amount up to about 60% by weight of the total matrix.
  • the matrix may release the active ingredient from within seconds to hours of application depending on the desired release profile.
  • the active ingredient is releasable from the matrix within at least two hours following application to one or more membranes in the buccal cavity, preferably within one hour of application and even more preferably within 40 minutes of application. Most preferably, dissolution occurs within 12 to 15 minutes.
  • the matrix should be dissolved within 5 minutes of application.
  • prosal delivery system refers to a delivery system wherein an active ingredient is provided for absorption across one or more membranes in the mouth, including the buccal mucosa, buccal gingiva, mucous membrane of the tongue, sublingual membrane and the soft palate.
  • the term encompasses all suitable dosage forms capable of manufacture using a normal dry powder process and compression using a standard tabletting machine.
  • references to an “active ingredient” includes a therapeutic or prophylactic agent, drug, pro-drug, drug complex, drug intermediate, diagnostic agent, enzyme, medicine, plant extract, herbal concoction, phytochemical, proteins, antibody, nanobody, antibody fragment, antibody directed enzyme pro-drug therapy (ADEPT), bioactive compound, nutraceutical or dietary supplement.
  • ADEPT antibody directed enzyme pro-drug therapy
  • matrix refers to a solid or semi-solid monolithic material containing one or more dissolved or dispersed active ingredients closely associated with a surrounding, rate-controlling heterogenous material where the active ingredient(s) are released when the matrix is placed in direct contact with a moist diffusion membrane.
  • the solid or semi solid monolithic material can include a range of materials known in the art of pharmaceutical drug delivery to emulsify, solubilize, complex or deliver any biologically active lipophilic or hydrophilic compound across a membrane.
  • PEG polyethylene glycol
  • the choice of PEG will be related to whether zero or first order release is desired.
  • the base is PEG 1450.
  • the polyethylene glycol can be used in the form of a PEG-fatty acid ester having surfactant properties.
  • suitable PEG-fatty acid esters include PEG-10 laurate, PEG-12 laurate, PEG-20 laurate, PEG-32 laurate, PEG-32 dilaurate, PEG-12 oleate, PEG-15 oleate, PEG-20 oleate, PEG-20 dioleate, PEG-32 oleate, PEG-200 oleate, PEG-400 oleate, PEG-15 stearate, PEG-32 distearate, PEG-40 stearate, PEG-100 stearate, PEG-20 dilaurate, PEG-25 glyceryl trioleate, PEG-32 dioleate, PEG-20 glyceryl laurate, PEG-30 glyceryl laurate, PEG-20 glyceryl stearate, PEG-20 glyceryl oleate, PEG-30
  • suspending agent is sufficient to improve the texture and consistency of the delivery system.
  • suspending agents are those in the gum-yielding plant group such as tetragonolobus, Acacia glaucophylla, Acacia abyssinica, Acacia nilotica, Acacia gummifera and Acacia arabica .
  • Other suitable suspending agents include silica gel and suspension polymers such as kollidon, cremaphor, kollicoat, solutol and ludipress.
  • the flowing agent also known as lubricant
  • the flowing agent is present in an amount sufficient for the prevention of adhesion, especially during the manufacturing process.
  • a suitable example of a flowing agent is magnesium stearate.
  • the buccal delivery system comprises a sufficient amount of a sweetener to improve the organoleptic properties of the dosage form.
  • suitable sweeteners include sucrose, sucralose; zinc gluconate; ethyl maltitol; glycine; acesulfame-K; aspartame; saccharin; fructose; xylitol; honey; corn syrup, golden syrup, misri, spray dried licorice root; glycerrhizine; dextrose; sodium gluconate; stevia powder; glucono delta-lactone; ethyl vanillin; vanillin; normal and high-potency sweeteners or syrups or salts thereof.
  • a high-intensity sweetener selected from the group consisting of aspartame, sucralose, and acesulfame-K is used.
  • the present invention provides a method of manufacturing a dosage formulation capable of delivering one or more active ingredients across one or more membranes within the buccal cavity, said method comprising the steps of:
  • suitable active ingredients include, but are not limited to, anti-infective agents (antibiotics), eye, ear, nose and throat preparations, anti-neoplastic agents including antibody, nanobody, antibody fragment(s), antibody directed enzyme pro-drug therapy (ADEPT), gastrointestinal drugs, respiratory agents, arthritic agents, blood formation and coagulation agents, diagnostic agents, photosensitisers (eg porphyrins and agents which stimulate natural porphyrin production), statins, naproxyn, indole-3-acetic acid, hormones and synthetic substitutes, cardiovascular drugs, skin and mucous membrane preparations, NSAIDs, analgesics, muscle spasm medications, anti-inflammatory agents, central nervous system drugs, dietary supplements, diabetic agents, and electrolyte and water balance agents, mixtures thereof and pro-drugs, drug complexes, drug intermediates, enzyme, vitamins and protein complexes thereof.
  • anti-infective agents antibiotics
  • eye ear, nose and throat preparations
  • anti-neoplastic agents
  • hormones of natural or synthetic origin selected from the hormone group comprising insulin, triamcinolone, testosterone, levonorgestrel, estradiol, phytoestrogen, estrone, dexamethasone, ethynodiol, prednisone, desogestrel, cyproterone, norethindrone, megestrol, hydrocortisone, danazol, cortisone acetate, aviane, nandrolone, fluoxymesterone, fludrocortisone, fluoxymesterone dexamethasone levora fludrocortisone low-ogestrel methylprednisolone, necon, levonorgestrel, estropipate, levoxyl, methimazole, propylthiouracil desmopressin, prednisolone orgestrel norethindrone triamcinolone trivora zovia gestodene, alfa
  • the active ingredient is a bisphosphonic acid or a bisphosphonate salt useful in the treatment of a bone resorptive condition.
  • a bisphosphonic acid includes one or more acids as well as pharmaceutically acceptable salts and derivatives thereof. This term may be used to refer to a salt form such as “biphosphonate”.
  • Preferred bisphosphonic acids and their salts include the group comprising alendronate, etidronate, pamidronate, tiludronate and risedronate compounds. Even more preferably, the bisphosphonate is alendronate selected from the group comprising anhydrous alendronate or hydrated alendronate salts, such as sodium alendronate.
  • the buccal delivery system of the present invention may contain two or more active agents.
  • the active ingredients may be released at the same time, ie simultaneously, or at differential rates.
  • a preferred combination is one or more bisphosphonic acids (or salts thereof) with one or more hormones used in hormone replacement therapy, such as estradiol, progesterone, testosterone and/or dehydroepiandrosterone (DHEA).
  • hormone replacement therapy such as estradiol, progesterone, testosterone and/or dehydroepiandrosterone (DHEA).
  • the art of efficient drug delivery also requires that a drug be both soluble in the aqueous biological medium and in an appropriate form to permit transport of either individual drug molecules or very small aggregates of the drug molecules.
  • the buccal delivery system may further comprise one or more other pharmaceutically acceptable carriers and/or excipients, such as but not limited to binding agents, flavouring agents, colouring agents, solubility enhancers, disintegrants, fillers, proteins, co-factors, emulsifiers, and solubilizing or complexing agents.
  • these excipients will improve delivery of the active ingredient across a membrane. Suitable excipients will be known to those skilled in the art.
  • emulsifier which may be suitable is tocopherol polyethylene glycol 1000 succinate (TPGS).
  • TPGS tocopherol polyethylene glycol 1000 succinate
  • complexing agents are compounds containing amine groups or other nitrogen functional groups such as amino acids, proteins, amine functional sterols and phospholipids containing amine functional groups.
  • Suitable surfactants may be amphoteric, zwitterionic, or cationic.
  • Preferred complexing agents of this type include water-soluble cationic polymers with a quaternary ammonium functional group on the polymer backbone and water-soluble, cationic guar jaguar gums).
  • the buccal delivery system comprises a binding and gelling agent such as hydroxypropyl methocellulose.
  • the buccal delivery system further comprises a colouring agent which may be a dye or a pigment.
  • a colouring agent which may be a dye or a pigment.
  • Suitable colouring agents are well known in the art and include curcumin, carotenoids, sunset yellow, tartrazine, indigo dyes, quino-phthalene dyes and triphenyl methane dyes.
  • the buccal delivery system further comprises a flavouring agent for improving organoleptic properties.
  • suitable flavouring agents are well known in the art and include almond oil; babassu oil; borage oil; blackcurrant seed oil; canola oil; castor oil; coconut oil; corn oil; cottonseed oil; evening primrose oil; grapeseed oil; groundnut oil; mustard seed oil; olive oil; palm oil; palm kernel oil; peanut oil; grapeseed oil; safflower oil; sesame oil; shark liver oil; soybean oil; sunflower oil; hydrogenated castor oil; hydrogenated coconut oil; hydrogenated palm oil; hydrogenated soybean oil; hydrogenated vegetable oil; hydrogenated cottonseed and castor oil; partially hydrogenated soybean oil; soy oil; glyceryl tricaproate; glyceryl tricaprylate; glyceryl tricaprate; glyceryl triundecanoate; glyceryl trilaurate; glyceryl trioleate; glyceryl trilinoleate;
  • the buccal dosage forms are useful as sustained release compositions.
  • sustained release also referred to as “extended release” is used in its conventional sense to refer to a drug formulation that provides for gradual release of a drug over an extended period of time, and that preferably, although not necessarily, results in substantially constant blood levels of a drug over an extended time period.
  • the present invention further contemplates methods of treatment and/or prophylaxis of medical conditions in mammals and, in particular, humans by the administration of a drug using a delivery system according to the invention.
  • FIG. 1 is a diagrammatic representation showing the results obtained for oestradiol using a buccal delivery system according to the invention in Example 3.
  • FIG. 2 is a diagrammatic representation showing the results obtained for progesterone using a buccal delivery system according to the invention in Example 3.
  • FIG. 3 is a diagrammatic representation showing the results obtained for testosterone using a buccal delivery system according to the invention in Example 3.
  • FIG. 4 is a diagrammatic representation showing the results obtained for dehydroepiandrosterone-sulphate using a buccal delivery system according to the invention in Example 3.
  • FIG. 5 is a diagrammatic representation showing the results obtained for all of the hormones tested using a buccal delivery system according to the invention in Example 3.
  • FIG. 6 is a tabular representation showing the results obtained for all of the hormones tested using a buccal delivery system according to the invention in Example 3.
  • This example shows the process for preparation of troches as per the prior art.
  • Magnesium Stearate 0.05-2% by weight
  • Kollidon 0.05-2% by weight
  • Stevia 0.05-2% by weight
  • Active Ingredient up to 60% by weight
  • Standard dry blending was performed in a horizontal low-energy laboratory blender for 60 mins. Powder mixtures were subsequently blended with PEG for 5 mins, and directly compressed via TabletPress Inc Benchtop single press tablet punch.
  • Dissolution times for these LINGUET tablets range from 10 to 20 mins, while a slightly longer period of 15-20 mins was required for complete dissolution following buccal administration.
  • This example investigated the bioavailability of hormone replacement therapy active ingredients using the buccal delivery system of the invention in a clinical trial in a hospital.
  • the trial was conducted with approval of an ethics committee within the hospital.
  • LINGUET tablets were generated containing 17-p-oestradiol (0.5 mg), progesterone (200 mg), testosterone (2.0 mg) and DHEA (10.0 mg).
  • the excipients in the LINGUET tablets consisted of silica gel, magnesium stearate, acacia, stevia and polyethylene glycol with a wildberry flavour.
  • the LINGUET tablets employed in this trial were formulated in a single batch for the study using the process according to the invention as described in example 2 above.
  • the LINGUET tablets were provided by Richard Stenlake Compounding Pharmacist (Bondi Junction, Australia).
  • Subjects did not have a history of cancer of the breast or uterus, thrombosis, embolism, hypertension, diabetes, hyperlipidaemia, obesity or were smokers. They also did not have any clinically significant abnormalities on routine biochemical and haematological screening.
  • Subjects discontinued their prescribed HRT therapy as well as any herbal or alternative medicines not less than three days prior to the first study day. Subjects presented to the Clinical Trials Centre on the morning of each study day after an overnight fast. An indwelling cannula was inserted into a forearm vein and a baseline blood specimen collected.
  • a half-LINGUET tablet was placed in the buccal cavity (between the cheek and the gum) and allowed to dissolve. Subjects were instructed not to swallow the formulation. Dissolution of the formulation in the buccal cavity took up to 40 min. Subjects rinsed their mouths with water at 45 min. Blood samples were collected via the cannula at timed intervals over 24 h. Subjects were discharged, but continued to take half a LINGUET tablet, twice daily, for the following two weeks. Subjects then re-presented to the Clinical Trials Centre where the morning dose was taken and further blood samples were collected at timed intervals over the dosage interval of 12 h.
  • Blood samples were schedule for collection following the single dose at the following times: Pre-dose (0), 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 12.0, 16.0, 20.0 and 24.0 h following the single dose, and at pre-dose (0), 0.25. 0.5, 0.75, 1.0, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 10.0 and 12 h after the two-week dosing interval (steady-state). Actual times were recorded, and these were used for the pharmacokinetic calculations.
  • Saliva was collected according to the standardized directions provided by the laboratory, Australian Reference Laboratories (Melbourne), and stored frozen ( ⁇ 20° C.) prior to shipping for hormonal analysis. In brief, subjects rinsed their mouths thoroughly with water and waited 5-10 min before swallowing any saliva in the mouth. Subjects then expressed saliva directly into the collection tubes.
  • Saliva samples were obtained for single dose estimation at the following times: pre-dose (0), and 1.0, 4.0, 8.0, 12.0, 16.0 and 24 h after dosing.
  • saliva was collected at pre-dose (0), and 1.0, 4.0, 8.0 and 12.0 h after LINGUET tablet administration.
  • Plasma concentrations of hormones were determined using routine validated, radioimmunoassay techniques in the hospital laboratory (Sydpath, St Vincent's Hospital, Sydney).
  • the laboratory is an accredited pathology provider that participates in national quality assurance programmes for hormonal analysis.
  • Hormone concentrations in saliva were conducted by the Analytical Reference Laboratories (Melbourne) using validated, commercial radioimmunoassays. This laboratory is similarly an accredited pathology provider.
  • DHEA was monitored as the sulphate metabolite (DHEAS), not as the administered hormone.
  • Oestradiol Single and multiple dosing of the LINGUET tablet produced very similar mean concentration-time profiles for oestrogen in plasma. Substantial intersubject variability on concentrations was evident (Tables 3 and 4).
  • Testosterone Single and multiple dosing of the LINGUET tablet also produced virtually super-imposable mean concentration-time profiles for testosterone in plasma with markedly increased concentrations for up to 4 hours, and a return to pre-treatment values within approximately 8 hours. Absorption of this hormone was more rapid than for the others with peak concentrations occurring at a mean of 0.6 hr (Tables 3 and 4).
  • Progesterone demonstrated the greatest accumulation on dosage to steady-state (Table 3). Elimination of this hormone appeared to be biphasic with a secondary peak evident at approximately 4 hr both following single and multiple dosing. Concentrations decreased to below those generally associated with biological activity in the endometrium within five hours.
  • DHEA Dehydroepiandrosterone
  • Ratios of saliva top plasma was very variable (Table 5—see FIG. 6 ).
  • Plasma hormones Each of the four hormones, oestradiol, progesterone, testosterone and dehydroepiandrosterone (the latter monitored as the active sulphate metabolite) were readily absorbed from the LINGUET tablet and achieved concentrations found in normal young menstruating women. Peak concentrations were achieved quite quickly, with a return to baseline between 4 and 8 hours after the single dose. The profiles at steady-state were very similar for oestrogen and testosterone reflecting their short half-lives with respect to the dosing interval. By contrast, at steady-state progesterone was sustained at concentrations usually associated with physiological and biological activity in young normal women. If this sustained concentration of progesterone is shown to produce inhibition of mitosis in the endometrium or result in develop of secretory change, then this route of delivery of progesterone could be utilised for management of post-menopausal symptoms.
  • the advantage of the buccal route of delivery is that it allowed rapid absorption of the hormones and physiological concentrations were achieved.
  • This formulation avoids the first-pass metabolism associated with oral administration, while also obviating the difficulties commonly associated with transdermal application, namely erratic and poor absorption.
  • Table 5 shows the results of a single dose LINGUET tablet on day 1 when testing mean hormone concentrations in blood and saliva.
  • the LINGUET tablets which contained the buccal delivery system according to the invention delivered the hormones via the buccal cavity into the blood.
  • the results obtained are comparable with those published for the prior art troches in Wren et al, “Pharmacokinetics of estradiol, progesterone, testosterone and dehydroepiandrosterone after transbuccal administration to postmenopausal women” Climacteric 2003, 6:104-111.

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Cited By (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20080317844A1 (en) * 2005-04-15 2008-12-25 Clarus Therapeutics, Inc. Pharmaceutical Delivery Systems for Hydrophobic Drugs and Compositions Compositions Comprising Same
US20100136105A1 (en) * 1999-06-30 2010-06-03 Lipocine, Inc. Pharmaceutical compositions and dosage forms for administration of hydrophobic drugs
US20110142945A1 (en) * 2002-12-17 2011-06-16 Lipocine Inc. Hydrophobic Active Agent Compositions and Related Methods
WO2011101734A2 (en) 2010-02-22 2011-08-25 Lupin Limited Taste-masked powder for suspension compositions of methylprednisolone
US20120058962A1 (en) * 2009-05-20 2012-03-08 Lingual Conseqna Pty Ltd. Buccal and/or sublingual therapeutic formulation
US8492369B2 (en) 2010-04-12 2013-07-23 Clarus Therapeutics Inc Oral testosterone ester formulations and methods of treating testosterone deficiency comprising same
US8778922B2 (en) 2009-01-08 2014-07-15 Lipocine Inc. Steroidal compositions
US9034858B2 (en) 2010-11-30 2015-05-19 Lipocine Inc. High-strength testosterone undecanoate compositions
US9358241B2 (en) 2010-11-30 2016-06-07 Lipocine Inc. High-strength testosterone undecanoate compositions
US9498485B2 (en) 2014-08-28 2016-11-22 Lipocine Inc. Bioavailable solid state (17-β)-hydroxy-4-androsten-3-one esters
US20180015102A1 (en) * 2012-11-14 2018-01-18 Abon Pharmaceuticals, Llc Oral Transmucosal Drug Delivery System
US10561615B2 (en) 2010-12-10 2020-02-18 Lipocine Inc. Testosterone undecanoate compositions
US11433083B2 (en) 2010-11-30 2022-09-06 Lipocine Inc. High-strength testosterone undecanoate compositions
US11559530B2 (en) 2016-11-28 2023-01-24 Lipocine Inc. Oral testosterone undecanoate therapy
US11707467B2 (en) 2014-08-28 2023-07-25 Lipocine Inc. (17-ß)-3-oxoandrost-4-en-17YL tridecanoate compositions and methods of their preparation and use

Families Citing this family (56)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7776314B2 (en) 2002-06-17 2010-08-17 Grunenthal Gmbh Abuse-proofed dosage system
DE102005005446A1 (de) 2005-02-04 2006-08-10 Grünenthal GmbH Bruchfeste Darreichungsformen mit retardierter Freisetzung
DE10361596A1 (de) 2003-12-24 2005-09-29 Grünenthal GmbH Verfahren zur Herstellung einer gegen Missbrauch gesicherten Darreichungsform
US20070048228A1 (en) 2003-08-06 2007-03-01 Elisabeth Arkenau-Maric Abuse-proofed dosage form
DE10336400A1 (de) 2003-08-06 2005-03-24 Grünenthal GmbH Gegen Missbrauch gesicherte Darreichungsform
DE102004032049A1 (de) 2004-07-01 2006-01-19 Grünenthal GmbH Gegen Missbrauch gesicherte, orale Darreichungsform
DE102005005449A1 (de) 2005-02-04 2006-08-10 Grünenthal GmbH Verfahren zur Herstellung einer gegen Missbrauch gesicherten Darreichungsform
DE102007011485A1 (de) 2007-03-07 2008-09-11 Grünenthal GmbH Darreichungsform mit erschwertem Missbrauch
US8114448B2 (en) * 2008-01-21 2012-02-14 Himalaya Global Holdings Limited Herbal dental care composition, method of manufacturing the same and use thereof
TWI454288B (zh) 2008-01-25 2014-10-01 Gruenenthal Chemie 藥物劑型
PT2273983T (pt) 2008-05-09 2016-10-28 Gruenenthal Gmbh Processo para a preparação de uma formulação em pó intermediária e uma forma de dosagem sólida final sob utilização de uma etapa de congelamento por atomização
US20120101427A1 (en) * 2009-04-28 2012-04-26 Gerard Farmer Novel photosensitizer formulations for oral administration
ES2560210T3 (es) 2009-07-22 2016-02-17 Grünenthal GmbH Forma de dosificación resistente a la manipulación para opiádes sensibles a la oxidación
CN102573805A (zh) 2009-07-22 2012-07-11 格吕伦塔尔有限公司 热熔挤出的控制释放剂型
EP2504019A2 (en) 2009-11-25 2012-10-03 ArisGen SA Mucosal delivery composition comprising a peptide complexed with a crown compound and/or a counter ion
UA107095C2 (uk) * 2009-12-14 2014-11-25 Антибіотичні мікрочастинки для інгаляції
RU2604676C2 (ru) 2010-09-02 2016-12-10 Грюненталь Гмбх Устойчивая к разрушению лекарственная форма, содержащая неорганическую соль
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EP2526971A1 (en) 2011-05-25 2012-11-28 ArisGen SA Mucosal delivery of drugs
LT2736495T (lt) 2011-07-29 2017-11-10 Grünenthal GmbH Sugadinimui atspari tabletė, pasižyminti greitu vaisto atpalaidavimu
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US9149528B2 (en) 2011-10-13 2015-10-06 Premier Dental Products Company Topical vitamin D oral supplement compositions
HUE055562T2 (hu) 2011-11-23 2021-11-29 Therapeuticsmd Inc Természetes kombinációjú hormon helyettesítõ kiszerelések, és terápiák ezekkel
US9301920B2 (en) 2012-06-18 2016-04-05 Therapeuticsmd, Inc. Natural combination hormone replacement formulations and therapies
JP6117249B2 (ja) 2012-02-28 2017-04-19 グリュネンタール・ゲゼルシャフト・ミト・ベシュレンクテル・ハフツング 薬理学的に活性な化合物および陰イオン性ポリマーを含むタンパーレジスタント剤形
CA2868142A1 (en) 2012-04-18 2013-10-24 Grunenthal Gmbh Tamper resistant and dose-dumping resistant pharmaceutical dosage form
US10064945B2 (en) 2012-05-11 2018-09-04 Gruenenthal Gmbh Thermoformed, tamper-resistant pharmaceutical dosage form containing zinc
US20150196640A1 (en) 2012-06-18 2015-07-16 Therapeuticsmd, Inc. Progesterone formulations having a desirable pk profile
US10806697B2 (en) 2012-12-21 2020-10-20 Therapeuticsmd, Inc. Vaginal inserted estradiol pharmaceutical compositions and methods
US10806740B2 (en) 2012-06-18 2020-10-20 Therapeuticsmd, Inc. Natural combination hormone replacement formulations and therapies
US20130338122A1 (en) 2012-06-18 2013-12-19 Therapeuticsmd, Inc. Transdermal hormone replacement therapies
US9877930B2 (en) 2012-10-12 2018-01-30 Premier Dental Products Company Topical ubiquinol oral supplement compositions with amorphous calcium phosphate
CA2886067C (en) * 2012-10-12 2021-04-06 Premier Dental Products Company Topical vitamin d oral supplement compositions
US10537581B2 (en) 2012-12-21 2020-01-21 Therapeuticsmd, Inc. Vaginal inserted estradiol pharmaceutical compositions and methods
US9180091B2 (en) 2012-12-21 2015-11-10 Therapeuticsmd, Inc. Soluble estradiol capsule for vaginal insertion
US10568891B2 (en) 2012-12-21 2020-02-25 Therapeuticsmd, Inc. Vaginal inserted estradiol pharmaceutical compositions and methods
US10471072B2 (en) 2012-12-21 2019-11-12 Therapeuticsmd, Inc. Vaginal inserted estradiol pharmaceutical compositions and methods
US11266661B2 (en) 2012-12-21 2022-03-08 Therapeuticsmd, Inc. Vaginal inserted estradiol pharmaceutical compositions and methods
US11246875B2 (en) 2012-12-21 2022-02-15 Therapeuticsmd, Inc. Vaginal inserted estradiol pharmaceutical compositions and methods
CN104147614B (zh) * 2013-05-15 2016-08-24 深圳先进技术研究院 一种阿伦膦酸功能化的聚乙二醇修饰的纳米颗粒及其制备方法
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US9737490B2 (en) 2013-05-29 2017-08-22 Grünenthal GmbH Tamper resistant dosage form with bimodal release profile
CN105682643B (zh) 2013-07-12 2019-12-13 格吕伦塔尔有限公司 含有乙烯-醋酸乙烯酯聚合物的防篡改剂型
AU2014356581C1 (en) 2013-11-26 2020-05-28 Grunenthal Gmbh Preparation of a powdery pharmaceutical composition by means of cryo-milling
EP3142646A1 (en) 2014-05-12 2017-03-22 Grünenthal GmbH Tamper resistant immediate release capsule formulation comprising tapentadol
RU2016143081A (ru) 2014-05-22 2018-06-26 Терапьютиксмд, Инк. Натуральные комбинированные гормонозаместительные составы и терапии
US9872835B2 (en) 2014-05-26 2018-01-23 Grünenthal GmbH Multiparticles safeguarded against ethanolic dose-dumping
WO2016126540A1 (en) * 2015-02-02 2016-08-11 Enspire Group LLC Stabilized dialkyl fumarate compositions
CN107889459A (zh) 2015-04-24 2018-04-06 格吕伦塔尔有限公司 具有立即释放和对溶剂萃取的抗性的抗篡改剂型
US10328087B2 (en) 2015-07-23 2019-06-25 Therapeuticsmd, Inc. Formulations for solubilizing hormones
EP3346991A1 (en) 2015-09-10 2018-07-18 Grünenthal GmbH Protecting oral overdose with abuse deterrent immediate release formulations
US10286077B2 (en) 2016-04-01 2019-05-14 Therapeuticsmd, Inc. Steroid hormone compositions in medium chain oils
KR20180126582A (ko) 2016-04-01 2018-11-27 쎄러퓨틱스엠디, 인코퍼레이티드 스테로이드 호르몬 약제학적 조성물
EP3257574A1 (en) * 2016-06-15 2017-12-20 Clariant International Ltd Method for producing a particle-shaped material
CN106267191A (zh) * 2016-09-03 2017-01-04 山西纳安生物科技有限公司 纳米抗体生物药透皮给药制剂系统及制备方法和应用
CN112964587B (zh) * 2021-02-08 2021-09-10 水利部交通运输部国家能源局南京水利科学研究院 一种模拟混凝土面板坝溃坝的离心模型试验装置及方法

Citations (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4146634A (en) * 1971-11-09 1979-03-27 Fisons Limited Composition
US5891465A (en) * 1996-05-14 1999-04-06 Biozone Laboratories, Inc. Delivery of biologically active material in a liposomal formulation for administration into the mouth
US5945117A (en) * 1998-01-30 1999-08-31 Pentech Pharmaceuticals, Inc. Treatment of female sexual dysfunction
US6117446A (en) * 1999-01-26 2000-09-12 Place; Virgil A. Drug dosage unit for buccal administration of steroidal active agents
US6180682B1 (en) * 1999-01-26 2001-01-30 Virgil A. Place Buccal drug delivery system for use in male contraception
US6319510B1 (en) * 1999-04-20 2001-11-20 Alayne Yates Gum pad for delivery of medication to mucosal tissues
US20020114833A1 (en) * 2000-12-06 2002-08-22 Abu-Izza Khawla A. Fast dissolving tablet
US20040019026A1 (en) * 2000-10-06 2004-01-29 Schwartz Arthur G. Compounds useful for treating hypertriglyceridemia
US20040028732A1 (en) * 2000-07-04 2004-02-12 Falkenhausen Christian Von Rapidly-decomposing administrable form for releasing active ingredients in the oral cavity or in bodily cavities
US20040037878A1 (en) * 2000-12-06 2004-02-26 Wyeth Fast dissolving tablet
US20060141027A1 (en) * 2003-06-10 2006-06-29 Valerio Cioli Sublingual administration of non-steroidal anti-inflammatory pharmacological substances

Family Cites Families (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1113492A (en) * 1964-05-20 1968-05-15 Bristol Myers Co Chewable tablets comprising a penicillin antibiotic
GB8522453D0 (en) 1985-09-11 1985-10-16 Lilly Industries Ltd Chewable capsules
US4764378A (en) * 1986-02-10 1988-08-16 Zetachron, Inc. Buccal drug dosage form
US5244668A (en) * 1988-10-14 1993-09-14 Zetachron, Inc. Low-melting moldable pharmaceutical excipient and dosage forms prepared therewith
US5324746A (en) * 1993-02-12 1994-06-28 Mckee Rex N Method of treating damaged mucosal and epithelial tissues with misoprostol
US5939091A (en) 1997-05-20 1999-08-17 Warner Lambert Company Method for making fast-melt tablets
JP4939680B2 (ja) * 1997-05-27 2012-05-30 武田薬品工業株式会社 固形製剤
DE69834255T2 (de) 1997-07-25 2006-09-28 Alpex Pharma S.A. Verfahren zur herstellung eines granulates, geeignet zur herstellung schnell-freisetzender, im mund löslicher tabletten
SE9703691D0 (sv) * 1997-10-10 1997-10-10 Astra Ab Pharmaceutical compositions
KR20010107754A (ko) * 2000-05-26 2001-12-07 민경윤 경구투여용 속용정의 제조 방법
GB2394415B (en) * 2002-10-22 2006-03-22 Gursharan Moonga Fast dissolving buccal tablets for rapid drug delivery
DK1599186T3 (da) * 2003-02-24 2013-07-08 Pharmaceutical Productions Inc System til administration af transmukalt lægemiddel

Patent Citations (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4146634A (en) * 1971-11-09 1979-03-27 Fisons Limited Composition
US5891465A (en) * 1996-05-14 1999-04-06 Biozone Laboratories, Inc. Delivery of biologically active material in a liposomal formulation for administration into the mouth
US5945117A (en) * 1998-01-30 1999-08-31 Pentech Pharmaceuticals, Inc. Treatment of female sexual dysfunction
US6193992B1 (en) * 1998-01-30 2001-02-27 Pentech Pharmaceuticals, Inc. Female sexual dysfunction treatment
US6117446A (en) * 1999-01-26 2000-09-12 Place; Virgil A. Drug dosage unit for buccal administration of steroidal active agents
US6180682B1 (en) * 1999-01-26 2001-01-30 Virgil A. Place Buccal drug delivery system for use in male contraception
US6319510B1 (en) * 1999-04-20 2001-11-20 Alayne Yates Gum pad for delivery of medication to mucosal tissues
US20040028732A1 (en) * 2000-07-04 2004-02-12 Falkenhausen Christian Von Rapidly-decomposing administrable form for releasing active ingredients in the oral cavity or in bodily cavities
US20040019026A1 (en) * 2000-10-06 2004-01-29 Schwartz Arthur G. Compounds useful for treating hypertriglyceridemia
US20020114833A1 (en) * 2000-12-06 2002-08-22 Abu-Izza Khawla A. Fast dissolving tablet
US20040037878A1 (en) * 2000-12-06 2004-02-26 Wyeth Fast dissolving tablet
US20060141027A1 (en) * 2003-06-10 2006-06-29 Valerio Cioli Sublingual administration of non-steroidal anti-inflammatory pharmacological substances

Cited By (45)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20100136105A1 (en) * 1999-06-30 2010-06-03 Lipocine, Inc. Pharmaceutical compositions and dosage forms for administration of hydrophobic drugs
US20110142945A1 (en) * 2002-12-17 2011-06-16 Lipocine Inc. Hydrophobic Active Agent Compositions and Related Methods
US8778917B2 (en) 2005-04-15 2014-07-15 Clarus Therapeutics, Inc. Pharmaceutical delivery systems for hydrophobic drugs and compositions comprising same
US11331325B2 (en) 2005-04-15 2022-05-17 Clarus Therapeutics, Inc. Pharmaceutical delivery systems for hydrophobic drugs and compositions comprising same
US11179402B2 (en) 2005-04-15 2021-11-23 Clarus Therapeutics, Inc. Pharmaceutical delivery systems for hydrophobic drugs and compositions comprising same
US8241664B2 (en) 2005-04-15 2012-08-14 Clarus Therapeutics, Inc Pharmaceutical delivery systems for hydrophobic drugs and compositions comprising same
US20080317844A1 (en) * 2005-04-15 2008-12-25 Clarus Therapeutics, Inc. Pharmaceutical Delivery Systems for Hydrophobic Drugs and Compositions Compositions Comprising Same
US8778916B2 (en) 2005-04-15 2014-07-15 Clarus Therapeutics, Inc. Oral testosterone ester formulations and methods of treating testosterone deficiency comprising same
US8828428B1 (en) 2005-04-15 2014-09-09 Clarus Therapeutics, Inc. Pharmaceutical delivery systems for hydrophobic drugs and compositions comprising same
US8865695B2 (en) 2009-01-08 2014-10-21 Lipocine Inc. Steroidal compositions
US11304960B2 (en) 2009-01-08 2022-04-19 Chandrashekar Giliyar Steroidal compositions
US11052096B2 (en) 2009-01-08 2021-07-06 Lipocine Inc. Steroidal compositions
US8778922B2 (en) 2009-01-08 2014-07-15 Lipocine Inc. Steroidal compositions
US20120058962A1 (en) * 2009-05-20 2012-03-08 Lingual Conseqna Pty Ltd. Buccal and/or sublingual therapeutic formulation
WO2011101734A2 (en) 2010-02-22 2011-08-25 Lupin Limited Taste-masked powder for suspension compositions of methylprednisolone
US10543219B2 (en) 2010-04-12 2020-01-28 Clarus Therapeutics, Inc. Oral testosterone ester formulations and methods of treating testosterone deficiency comprising same
US8492369B2 (en) 2010-04-12 2013-07-23 Clarus Therapeutics Inc Oral testosterone ester formulations and methods of treating testosterone deficiency comprising same
US11426416B2 (en) 2010-04-12 2022-08-30 Clarus Therapeutics, Inc. Oral testosterone ester formulations and methods of treating testosterone deficiency comprising same
US11179403B2 (en) 2010-04-12 2021-11-23 Clarus Therapeutics, Inc. Oral testosterone ester formulations and methods of treating testosterone deficiency comprising same
US10617696B2 (en) 2010-04-12 2020-04-14 Clarus Therapeutics, Inc. Oral testosterone ester formulations and methods of treating testosterone deficiency comprising same
US10716794B2 (en) 2010-11-30 2020-07-21 Lipocine Inc. High-strength testosterone undecanoate compositions
US9480690B2 (en) 2010-11-30 2016-11-01 Lipocine Inc. High-strength testosterone undecanoate compositions
US10226473B2 (en) 2010-11-30 2019-03-12 Lipocine Inc. High-strength testosterone undecanoate compositions
US9943527B2 (en) 2010-11-30 2018-04-17 Lipocine Inc. High-strength testosterone undecanoate compositions
US11433083B2 (en) 2010-11-30 2022-09-06 Lipocine Inc. High-strength testosterone undecanoate compositions
US9034858B2 (en) 2010-11-30 2015-05-19 Lipocine Inc. High-strength testosterone undecanoate compositions
US9757390B2 (en) 2010-11-30 2017-09-12 Lipocine Inc. High-strength testosterone undecanoate compositions
US10799513B2 (en) 2010-11-30 2020-10-13 Lipocine Inc. High-strength testosterone undecanoate compositions
US11364250B2 (en) 2010-11-30 2022-06-21 Lipocine Inc. High-strength testosterone undecanoate compositions
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US10973833B2 (en) 2010-11-30 2021-04-13 Lipocine Inc. High-strength testosterone undecanoate compositions
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US9205057B2 (en) 2010-11-30 2015-12-08 Lipocine Inc. High-strength testosterone undecanoate compositions
US9949985B2 (en) 2010-11-30 2018-04-24 Lipocine Inc. High-strength testosterone undecanoate compositions
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US9358241B2 (en) 2010-11-30 2016-06-07 Lipocine Inc. High-strength testosterone undecanoate compositions
US10561615B2 (en) 2010-12-10 2020-02-18 Lipocine Inc. Testosterone undecanoate compositions
US10821118B2 (en) * 2012-11-14 2020-11-03 Abon Pharmaceuticals Llc Oral transmucosal drug delivery system
US20180015102A1 (en) * 2012-11-14 2018-01-18 Abon Pharmaceuticals, Llc Oral Transmucosal Drug Delivery System
US11298365B2 (en) 2014-08-28 2022-04-12 Lipocine Inc. Bioavailable solid state (17-β)-hydroxy-4-androsten-3-one esters
US9498485B2 (en) 2014-08-28 2016-11-22 Lipocine Inc. Bioavailable solid state (17-β)-hydroxy-4-androsten-3-one esters
US9757389B2 (en) 2014-08-28 2017-09-12 Lipocine Inc. Bioavailable solid state (17-β)-hydroxy-4-androsten-3-one esters
US11707467B2 (en) 2014-08-28 2023-07-25 Lipocine Inc. (17-ß)-3-oxoandrost-4-en-17YL tridecanoate compositions and methods of their preparation and use
US11872235B1 (en) 2014-08-28 2024-01-16 Lipocine Inc. Bioavailable solid state (17-β)-Hydroxy-4-Androsten-3-one esters
US11559530B2 (en) 2016-11-28 2023-01-24 Lipocine Inc. Oral testosterone undecanoate therapy

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CA2603649C (en) 2014-10-14
RU2007141365A (ru) 2009-05-20
RU2406480C2 (ru) 2010-12-20
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JP2008534629A (ja) 2008-08-28
US8828435B2 (en) 2014-09-09
HK1113657A1 (en) 2008-10-10
US20110123619A1 (en) 2011-05-26
WO2006105615A1 (en) 2006-10-12
CN101227892B (zh) 2013-06-05
EP1865925A1 (en) 2007-12-19
CA2603649A1 (en) 2006-10-12
EP1865925A4 (en) 2012-01-18
JP5256425B2 (ja) 2013-08-07
NZ562311A (en) 2009-10-30

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