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US20070020186A1 - Solid dosage formulations of narcotic drugs having improved buccal adsorption - Google Patents

Solid dosage formulations of narcotic drugs having improved buccal adsorption Download PDF

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Publication number
US20070020186A1
US20070020186A1 US11/186,925 US18692505A US2007020186A1 US 20070020186 A1 US20070020186 A1 US 20070020186A1 US 18692505 A US18692505 A US 18692505A US 2007020186 A1 US2007020186 A1 US 2007020186A1
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US
United States
Prior art keywords
solid dosage
fentanyl
formulations according
dosage formulations
narcotic
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Abandoned
Application number
US11/186,925
Inventor
Federico Stroppolo
Shahbaz Ardalan
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.)
Alpex Pharma SA
Original Assignee
Alpex Pharma SA
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Alpex Pharma SA filed Critical Alpex Pharma SA
Priority to US11/186,925 priority Critical patent/US20070020186A1/en
Assigned to ALPEX PHARMA S.A. reassignment ALPEX PHARMA S.A. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: ARDALAN, SHAHBAZ, STROPPOLO, FEDERICO
Priority to EP06776336.7A priority patent/EP1906961B1/en
Priority to BRPI0613769-5A priority patent/BRPI0613769A2/en
Priority to HUE06776336A priority patent/HUE027354T2/en
Priority to RS20160214A priority patent/RS54670B1/en
Priority to PL06776336T priority patent/PL1906961T3/en
Priority to US11/490,500 priority patent/US8574552B2/en
Priority to HRP20160327TT priority patent/HRP20160327T1/en
Priority to MX2007015480A priority patent/MX2007015480A/en
Priority to ES06776336.7T priority patent/ES2569228T3/en
Priority to TW095126670A priority patent/TW200727922A/en
Priority to CA2607360A priority patent/CA2607360C/en
Priority to KR1020087000576A priority patent/KR101326206B1/en
Priority to AU2006271870A priority patent/AU2006271870B2/en
Priority to SI200632040A priority patent/SI1906961T1/en
Priority to PCT/EP2006/007189 priority patent/WO2007009806A2/en
Priority to NZ563511A priority patent/NZ563511A/en
Priority to CNA2006800232888A priority patent/CN101208091A/en
Priority to RU2007149044/15A priority patent/RU2408373C2/en
Priority to JP2008521904A priority patent/JP5714797B2/en
Priority to DK06776336.7T priority patent/DK1906961T3/en
Priority to UAA200713973A priority patent/UA90518C2/en
Publication of US20070020186A1 publication Critical patent/US20070020186A1/en
Priority to IL187387A priority patent/IL187387A/en
Priority to ZA200710406A priority patent/ZA200710406B/en
Priority to NO20080827A priority patent/NO20080827L/en
Priority to MA30659A priority patent/MA29744B1/en
Priority to US14/017,642 priority patent/US10258693B2/en
Priority to CY20161100346T priority patent/CY1117470T1/en
Abandoned 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
    • A61K9/20—Pills, tablets, discs, rods
    • 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
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4468—Non condensed piperidines, e.g. piperocaine having a nitrogen directly attached in position 4, e.g. clebopride, fentanyl
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
    • A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P23/00—Anaesthetics
    • 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
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • 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]

Definitions

  • the present invention concerns solid dosage formulations of narcotic drugs having improved buccal adsorption.
  • the formulations of the invention are characterized by the introduction in a buccal formulation of a soluble organic compound having a primary, secondary or tertiary amine group.
  • buccal formulations are more and more popular for drug administrations. They exhibit in fact several advantages in comparison with other solid dosage forms; in particular, buccal formulations dissolve in the oral cavity without requiring water for ingestion, allowing the buccal adsorption of drugs coming into contact with the oral mucosa in dissolved form. Sometimes, buccal administration does not unfortunately always allow to obtain a fast onset of action of the drug, as the result of difficulties of the drug to cross the skin barrier of mucosa and to penetrate into the blood stream.
  • the amount of amine required in the formulation ranges between 0.1 to 500% of the moles of active component(s), more preferably 0.5 to 300% and most preferably 1 to 200%.
  • amines used in order to improve bioavailability according to the invention include Histidine, Arginine, Lysine, Triethanolamine, Trimethylamine, Betaine, Pyrrolidine, Guanidine, Cysteamine, Taurine and derivatives and analogues thereof.
  • Arginine is a preferred non-toxic amine.
  • Oral dispersible tablets containing 200 mcg of Fentanyl were obtained as follows:
  • a pharmacokinetic study was carried out on 6 fasting healthy volunteers treated with a buccal formulation prepared in accordance with example # 1A containing 200 mcg of Fentanyl. The results were compared with a pharmacokinetic study carried out on 6 healthy volunteers treated with a buccal formulation prepared in accordance with example # 1B containing 400 mcg of Fentanyl.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Physiology (AREA)
  • Zoology (AREA)
  • Nutrition Science (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Anesthesiology (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Neurosurgery (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The present invention provides solid dosage formulations of narcotic drugs with improved buccal adsorption. These improved characteristics are provided by the combination of the narcotic drug with an additional non-toxic soluble organic compound. The soluble organic compound contains a primary, secondary or tertiary amine group. The addition of this organic compound favorably alters the kinetics of mucosal penetration such that mucosal penetration times are decreased. This provides for a faster onset of action of the drug.

Description

  • The present invention concerns solid dosage formulations of narcotic drugs having improved buccal adsorption.
  • The formulations of the invention are characterized by the introduction in a buccal formulation of a soluble organic compound having a primary, secondary or tertiary amine group.
    • BACKGROUND OF THE INVENTION
  • Buccal formulations are more and more popular for drug administrations. They exhibit in fact several advantages in comparison with other solid dosage forms; in particular, buccal formulations dissolve in the oral cavity without requiring water for ingestion, allowing the buccal adsorption of drugs coming into contact with the oral mucosa in dissolved form. Sometimes, buccal administration does not unfortunately always allow to obtain a fast onset of action of the drug, as the result of difficulties of the drug to cross the skin barrier of mucosa and to penetrate into the blood stream.
    • DESCRIPTION OF THE INVENTION
  • Surprisingly, it has been found that adding a non-toxic amine to a buccal formulation, the penetration capacity of drugs is significantly improved, allowing to reach an higher and earlier blood concentration of drugs in comparison with formulations without amines.
  • The amount of amine required in the formulation ranges between 0.1 to 500% of the moles of active component(s), more preferably 0.5 to 300% and most preferably 1 to 200%.
  • Examples of amines used in order to improve bioavailability according to the invention include Histidine, Arginine, Lysine, Triethanolamine, Trimethylamine, Betaine, Pyrrolidine, Guanidine, Cysteamine, Taurine and derivatives and analogues thereof. Arginine is a preferred non-toxic amine.
  • Examples of active components that may be advantageously formulated in solid dosage form according to the invention include:
  • Alfentanil, Buprenorphine Butorphanol, Codeine, Diphenoxylate, Fentanyl, Heroin, Hydrocodone, Hydromorphone, Oxymorphone, Levophanol, Levallorphan, Loperamide, Meperidine, Morfine, Nalbuphine, Nalmefene, Nalorphine, Naloxone, Naltrexone, Remifentanyl, Sufentanil. Fentanyl is preferred.
  • The invention is illustrated by the following Examples:
    • EXAMPLE #1 Example #1A
  • Preparation of a Oral Dispersible Tablet Containing Amine (Arginine)
  • Oral dispersible tablets containing 200 mcg of Fentanyl were obtained as follows:
  • A) 1.05 g of Fentanyl and 50 g of PEG 600 were dissolved into 90 g of purified water.
  • B) 335.62 g of Sorbitol, 516.67 g of Mannitol, 26.67 g of aspartame and 10 g of Citric acid, were granulated together with a water solution containing PEG and Fentanyl citrate.
  • C) At the end of granulation and drying, 43.33 g of arginine free base and 16.67 g of magnesium stearate were added.
  • D) The product was blended until homogeneity and compressed in toroidal tablets having a diameter of 10 mm and weighing 300 mg each
    • Example #1B
  • Preparation of an Oral Dispersable Tablet without Amine (Arginine)
  • Oral dispersible tablets containing 400 mcg of Fentanyl have been obtained as follows:
  • E) 2.1 g of Fentanyl and 50 g of PEG 600 was dissolved into 90 g of purified water.
  • F) 455.62 g of Sorbitol, 455.62 g of Mannitol, 26.67 g of aspartame and 10 g of Citric acid, were granulated together with a water solution containing PEG and Fentanyl citrate.
  • G) The product was blended until homogeneity and compressed in toroidal tablets having a diameter of 10 mm and weighing 300 mg each
    • EXAMPLE # 2
  • A pharmacokinetic study was carried out on 6 fasting healthy volunteers treated with a buccal formulation prepared in accordance with example # 1A containing 200 mcg of Fentanyl. The results were compared with a pharmacokinetic study carried out on 6 healthy volunteers treated with a buccal formulation prepared in accordance with example # 1B containing 400 mcg of Fentanyl.
  • The results are reported in the following Table:
    Fentanyl
    strength per
    dosage Tmax Cmax AUC
    Example # 1A 200 mcg 48 minutes 496 pg/mL 2430
    Example # 1B 400 mcg 35 minutes 491 pg/mL 3331
  • Despite the dose of Fentanyl administered in the tablets described in example # 1A (200 mcg) is 50% of the dose described in example #1B (400 mcg), the pharmacokinetic parameters are similar, demonstrating a dramatic improvement of the Fentanyl bioavailability for the formulation of the invention.

Claims (6)

1. Solid dosage formulations of narcotic drugs in form of buccal tablets characterized by containing a non toxic amine.
2. Formulations according to claim 1, wherein the non-toxic amine is selected from Histidine, Arginine, Lysine, Triethanolamine, Trimethylamine, Betaine, Pyrrolidine, Guanidine, Cysteamine, Taurine and derivatives and analogues thereof.
3. Formulations according to claim 2 wherein the non-toxic amine is arginine.
4. Formulations according to claim 1 wherein the non-toxic amine is present in amounts ranging between 0.1 to 500% of the moles of active component(s), more preferably 0.5 to 300% and most preferably 1 to 200%.
5. Formulations according to claim 1 wherein the narcotic drug is selected from Alfentanil, Buprenorphine, Butorphanol, Codeine, Diphenoxylate, Fentanyl, Heroin, Hydrocodone, Hydromorphone, Oxymorphone, Levophanol, Levallorphan, Loperamide, Meperidine, Morfine, Nalbuphine, Nalmefene, Nalorphine, Naloxone, Naltrexone, Remifentanyl, Sufentanil.
6. Formulations according to claim 5 wherein the active ingredient is Fentanyl.
US11/186,925 2005-07-22 2005-07-22 Solid dosage formulations of narcotic drugs having improved buccal adsorption Abandoned US20070020186A1 (en)

Priority Applications (28)

Application Number Priority Date Filing Date Title
US11/186,925 US20070020186A1 (en) 2005-07-22 2005-07-22 Solid dosage formulations of narcotic drugs having improved buccal adsorption
UAA200713973A UA90518C2 (en) 2005-07-22 2006-07-21 Pharmaceutical composition in the form of a tablet suitable for dissolution in the buccal cavity, comprising a narcotic active ingredient and amine
SI200632040A SI1906961T1 (en) 2005-07-22 2006-07-21 Solid dosage formulations of fentanyl having improved buccal adsorption
PCT/EP2006/007189 WO2007009806A2 (en) 2005-07-22 2006-07-21 Solid dosage formulations of narcotic drugs having improved buccal adsorption
HUE06776336A HUE027354T2 (en) 2005-07-22 2006-07-21 Solid dosage formulations of fentanyl having improved buccal adsorption
RS20160214A RS54670B1 (en) 2005-07-22 2006-07-21 SOLID DOSAGE FORMULATION OF FENTANIL WITH IMPROVED BUCHAL ADSORPTION
PL06776336T PL1906961T3 (en) 2005-07-22 2006-07-21 Solid dosage formulations of fentanyl having improved buccal adsorption
US11/490,500 US8574552B2 (en) 2005-07-22 2006-07-21 Solid dosage formulations of narcotic drugs having improved buccal adsorption
HRP20160327TT HRP20160327T1 (en) 2005-07-22 2006-07-21 SOLID FENTANIL DOSAGE FORMS WITH IMPROVED BUCHAL ABSORPTION
MX2007015480A MX2007015480A (en) 2005-07-22 2006-07-21 Solid dosage formulations of narcotic drugs having improved buccal adsorption.
ES06776336.7T ES2569228T3 (en) 2005-07-22 2006-07-21 Formulations of solid pharmaceutical forms of fentanyl that have better oral adsorption
TW095126670A TW200727922A (en) 2005-07-22 2006-07-21 Solid dosage formulations of narcotic drugs having improved buccal adsorption
CA2607360A CA2607360C (en) 2005-07-22 2006-07-21 Solid dosage formulations of narcotic drugs having improved buccal adsorption
KR1020087000576A KR101326206B1 (en) 2005-07-22 2006-07-21 Solid dosage formulations of narcotic drugs having improved buccal adsorption
AU2006271870A AU2006271870B2 (en) 2005-07-22 2006-07-21 Solid dosage formulations of narcotic drugs having improved buccal adsorption
EP06776336.7A EP1906961B1 (en) 2005-07-22 2006-07-21 Solid dosage formulations of fentanyl having improved buccal adsorption
CNA2006800232888A CN101208091A (en) 2005-07-22 2006-07-21 Solid pharmaceutical preparations of narcotics that facilitate oral absorption
DK06776336.7T DK1906961T3 (en) 2005-07-22 2006-07-21 FIXED DOSAGE FORMS OF FENTANYL WITH IMPROVED BUCHAL ADSORPTION
NZ563511A NZ563511A (en) 2005-07-22 2006-07-21 Solid dosage formulations of narocotic drugs having improved buccal adsorption
RU2007149044/15A RU2408373C2 (en) 2005-07-22 2006-07-21 Solid dosage forms of narcotic drugs of enhanced absorption in transbuccal administration
JP2008521904A JP5714797B2 (en) 2005-07-22 2006-07-21 Solid dosage formulation of anesthetic with improved absorption in the oral cavity
BRPI0613769-5A BRPI0613769A2 (en) 2005-07-22 2006-07-21 solid narcotic drug dosage formulations having improved buccal adsorption
IL187387A IL187387A (en) 2005-07-22 2007-11-15 Solid dosage formulations of narcotic drugs having improved buccal adsorption
ZA200710406A ZA200710406B (en) 2005-07-22 2007-11-30 Solid dosage formulations of narcotic drugs having improved buccal absorption
NO20080827A NO20080827L (en) 2005-07-22 2008-02-15 Solid dosage formulations of narcotic drugs that have improved buccal adsorption
MA30659A MA29744B1 (en) 2005-07-22 2008-02-18 SOLID DOSAGE FORMULATIONS OF MEDICAMENTS HAVING IMPROVED ORAL ADSORPTION
US14/017,642 US10258693B2 (en) 2005-07-22 2013-09-04 Solid dosage formulations of narcotic drugs having improved buccal adsorption
CY20161100346T CY1117470T1 (en) 2005-07-22 2016-04-26 SOLID DOSAGE PREPARATIONS WITH IMPROVED ANIMAL ADJUSTMENT

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US11/186,925 US20070020186A1 (en) 2005-07-22 2005-07-22 Solid dosage formulations of narcotic drugs having improved buccal adsorption

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US11/490,500 Continuation-In-Part US8574552B2 (en) 2005-07-22 2006-07-21 Solid dosage formulations of narcotic drugs having improved buccal adsorption

Publications (1)

Publication Number Publication Date
US20070020186A1 true US20070020186A1 (en) 2007-01-25

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Family Applications (3)

Application Number Title Priority Date Filing Date
US11/186,925 Abandoned US20070020186A1 (en) 2005-07-22 2005-07-22 Solid dosage formulations of narcotic drugs having improved buccal adsorption
US11/490,500 Expired - Fee Related US8574552B2 (en) 2005-07-22 2006-07-21 Solid dosage formulations of narcotic drugs having improved buccal adsorption
US14/017,642 Expired - Lifetime US10258693B2 (en) 2005-07-22 2013-09-04 Solid dosage formulations of narcotic drugs having improved buccal adsorption

Family Applications After (2)

Application Number Title Priority Date Filing Date
US11/490,500 Expired - Fee Related US8574552B2 (en) 2005-07-22 2006-07-21 Solid dosage formulations of narcotic drugs having improved buccal adsorption
US14/017,642 Expired - Lifetime US10258693B2 (en) 2005-07-22 2013-09-04 Solid dosage formulations of narcotic drugs having improved buccal adsorption

Country Status (26)

Country Link
US (3) US20070020186A1 (en)
EP (1) EP1906961B1 (en)
JP (1) JP5714797B2 (en)
KR (1) KR101326206B1 (en)
CN (1) CN101208091A (en)
AU (1) AU2006271870B2 (en)
BR (1) BRPI0613769A2 (en)
CA (1) CA2607360C (en)
CY (1) CY1117470T1 (en)
DK (1) DK1906961T3 (en)
ES (1) ES2569228T3 (en)
HR (1) HRP20160327T1 (en)
HU (1) HUE027354T2 (en)
IL (1) IL187387A (en)
MA (1) MA29744B1 (en)
MX (1) MX2007015480A (en)
NO (1) NO20080827L (en)
NZ (1) NZ563511A (en)
PL (1) PL1906961T3 (en)
RS (1) RS54670B1 (en)
RU (1) RU2408373C2 (en)
SI (1) SI1906961T1 (en)
TW (1) TW200727922A (en)
UA (1) UA90518C2 (en)
WO (1) WO2007009806A2 (en)
ZA (1) ZA200710406B (en)

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US20070207207A1 (en) * 2006-01-06 2007-09-06 Acelrx Pharmaceuticals, Inc. Bioadhesive drug formulations for oral transmucosal delivery
US20070260491A1 (en) * 2006-05-08 2007-11-08 Pamela Palmer System for delivery and monitoring of administration of controlled substances
US20070299687A1 (en) * 2006-06-23 2007-12-27 Pamela Palmer Inpatient system for patient-controlled delivery of oral transmucosal medications dosed as needed
US20080147044A1 (en) * 2006-01-06 2008-06-19 Acelrx Pharmaceuticals, Inc. Methods for administering small volume oral transmucosal dosage forms using a dispensing device
US20080164275A1 (en) * 2007-01-05 2008-07-10 Acelrx Pharmaceuticals, Inc. Storage and dispensing devices for administration of oral transmucosal dosage forms
US20090131479A1 (en) * 2006-01-06 2009-05-21 Acelrx Pharmaceuticals, Inc. Small-volume oral transmucosal dosage
US8252329B2 (en) 2007-01-05 2012-08-28 Acelrx Pharmaceuticals, Inc. Bioadhesive drug formulations for oral transmucosal delivery
US8357114B2 (en) 2006-01-06 2013-01-22 Acelrx Pharmaceuticals, Inc. Drug dispensing device with flexible push rod
US8535714B2 (en) 2006-01-06 2013-09-17 Acelrx Pharmaceuticals, Inc. Small volume oral transmucosal dosage forms containing sufentanil for treatment of pain
US8753308B2 (en) 2006-01-06 2014-06-17 Acelrx Pharmaceuticals, Inc. Methods for administering small volume oral transmucosal dosage forms using a dispensing device
US8865743B2 (en) 2006-01-06 2014-10-21 Acelrx Pharmaceuticals, Inc. Small volume oral transmucosal dosage forms containing sufentanil for treatment of pain
US8945592B2 (en) 2008-11-21 2015-02-03 Acelrx Pharmaceuticals, Inc. Sufentanil solid dosage forms comprising oxygen scavengers and methods of using the same
US11058856B2 (en) 2014-12-23 2021-07-13 Acelrx Pharmaceuticals, Inc. Systems, devices and methods for dispensing oral transmucosal dosage forms

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US8852638B2 (en) 2005-09-30 2014-10-07 Durect Corporation Sustained release small molecule drug formulation
US8497258B2 (en) 2005-11-12 2013-07-30 The Regents Of The University Of California Viscous budesonide for the treatment of inflammatory diseases of the gastrointestinal tract
WO2008153611A2 (en) 2007-05-25 2008-12-18 Qlt Usa, Inc. Sustained delivery formulations of risperidone compounds
CA2765033C (en) * 2009-06-12 2020-07-14 Meritage Pharma, Inc. Methods for treating gastrointestinal disorders
US9272044B2 (en) 2010-06-08 2016-03-01 Indivior Uk Limited Injectable flowable composition buprenorphine
GB2481017B (en) 2010-06-08 2015-01-07 Rb Pharmaceuticals Ltd Microparticle buprenorphine suspension
RU2476209C1 (en) * 2012-02-29 2013-02-27 Станислав Анатольевич Кедик Implanted drug preparation of naltrexone for treating alcohol- or opioid-dependent patients
US9993422B2 (en) 2012-04-18 2018-06-12 SpecGx LLC Immediate release, abuse deterrent pharmaceutical compositions
WO2014011830A1 (en) * 2012-07-12 2014-01-16 Mallinckrodt Llc Extended release, abuse deterrent pharmaceutical compositions
GB201404139D0 (en) 2014-03-10 2014-04-23 Rb Pharmaceuticals Ltd Sustained release buprenorphine solution formulations
CA3112030A1 (en) 2018-09-25 2020-04-02 SpecGx LLC Abuse deterrent immediate release capsule dosage forms

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