US20010036479A1 - Glyburide composition - Google Patents

Glyburide composition Download PDF

Info

Publication number
US20010036479A1
US20010036479A1 US09/735,334 US73533400A US2001036479A1 US 20010036479 A1 US20010036479 A1 US 20010036479A1 US 73533400 A US73533400 A US 73533400A US 2001036479 A1 US2001036479 A1 US 2001036479A1
Authority
US
United States
Prior art keywords
glyburide
drug
tablet
substance
capsule
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
US09/735,334
Inventor
Gillian Cave
Sarah Nicholson
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.)
Bristol Myers Squibb Co
Original Assignee
Bristol Myers Squibb Co
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority to US48370300A priority Critical
Application filed by Bristol Myers Squibb Co filed Critical Bristol Myers Squibb Co
Priority to US09/735,334 priority patent/US20010036479A1/en
Assigned to BRISTOL-MYERS SQUIBB COMPANY reassignment BRISTOL-MYERS SQUIBB COMPANY ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: CAVE, GILLIAN, NICHOLSON, SARAH J.
Publication of US20010036479A1 publication Critical patent/US20010036479A1/en
Application status is Abandoned legal-status Critical

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C311/00Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
    • C07C311/50Compounds containing any of the groups, X being a hetero atom, Y being any atom
    • C07C311/52Y being a hetero atom
    • C07C311/54Y being a hetero atom either X or Y, but not both, being nitrogen atoms, e.g. N-sulfonylurea
    • C07C311/57Y being a hetero atom either X or Y, but not both, being nitrogen atoms, e.g. N-sulfonylurea having sulfur atoms of the sulfonylurea groups bound to carbon atoms of six-membered aromatic rings
    • C07C311/59Y being a hetero atom either X or Y, but not both, being nitrogen atoms, e.g. N-sulfonylurea having sulfur atoms of the sulfonylurea groups bound to carbon atoms of six-membered aromatic rings having nitrogen atoms of the sulfonylurea groups bound to carbon atoms of rings other than six-membered aromatic rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/14Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00Systems containing only non-condensed rings
    • C07C2601/12Systems containing only non-condensed rings with a six-membered ring
    • C07C2601/14The ring being saturated

Abstract

The present invention relates to a physical form of the known drug substance glyburide, also known as glibenclamide, and chemically defined as 5-chloro-N-[2-[4-[[[(cyclohexylamino)-carbonyl]amino]sulfonyl]phenyl]ethyl]-2-methoxybenzamide (Merck Index, Tenth Edition, p. 642), as well as to dosage forms, e.g., tablets and capsules, incorporating said physical form of glyburide.

Description

  • This application is a continuation-in-part of U.S. Application Ser. No. 09/483,703 filed Jan. 14, 2000.[0001]
  • The present invention relates to a physical form of the known drug substance glyburide, also known as glibenclamide, and chemically defined as 5-chloro-N-[2-[4-[[[(cyclohexylamino)-carbonyl]amino]sulfonyl]phenyl]ethyl]-2-methoxybenzamide (Merck Index, Tenth Edition, p. 642), as well as to dosage forms, e.g., tablets and capsules, incorporating said physical form of glyburide. [0002]
  • Specifically, the physical form of glyburide which is the subject matter of this invention is glyburide having a defined particle size distribution. This particle size distribution provides an enhanced rate of dissolution of the glyburide compared to bulk glyburide, and it provides reproducible bioavailability in vivo. The glyburide of the invention can also be incorporated into a tablet or capsule matrix to enhance the physicochemical (e.g., rate of drug dissolution and absorption) properties desired. The preferred rates of dissolution and absorption herein provide for early onset of glyburide absorption, yet avoid the very high and rapidly achieved plasma drug concentrations (“spike”) that would be achieved with prior art formulations when attempting to provide for early onset of absorption. A very high and rapidly achieved concentration can lead to undesirable hypoglycemia. The glyburide of the physical form described in this invention achieves this early rate of absorption, yet also maintains exposure of the patient to drug (as measured by the area under the plasma drug concentration against time curve), and therefore maintains the efficacy of the formulation. [0003]
  • The glyburide of the subject invention, and formulations based on this material, have properties that are particularly suitable for use as oral preprandial secretagogues. [0004]
  • Glyburide of the physical form described in this invention can also be used in formulations combining it with other drugs used in the treatment of type II diabetes. Examples include, but would not be limited to, acarbose or other glycosidase inhibitors, rosiglitazone, pioglitazone or other thiazolidonediones, biguanides such as metformin fumarate, repaglinide and other “aglinides”. Glyburide with the particle size distribution as given in the current invention may be particularly useful in cases where co-formulation with drugs of high dose and high solubility are required. An example of such a drug used for the treatment of type II diabetes is the biguanide known as metformin (including its fumarate and hydrochloride salts). [0005]
  • Glyburide is a commercially available product indicated for the treatment of type II diabetes. Its mode of action is that of an insulin secretagogue, i.e., that of an agent which stimulates the secretion of insulin from patient's beta cells. (See U.S. Pat. Nos. 3,426,067; 3,454,635; 3,507,961 and 3,507,954.) Subsequent to the discovery of glyburide itself, glyburide compositions with enhanced bioavailability to that of the originally developed and marketed formulation became available, for example as described in U.S. Pat. No. 3,979,520 and 4,060,634. These patents describe the use of micronized or high surface area (e.g., 3 to 10 m[0006] 2/g) glyburide in combination with various pharmaceutically acceptable excipients to obtain enhanced bioavailability. Another composition in the prior art relates to the use of a spray dried lactose formulation of micronized glyburide having a narrow distribution of particle sizes. The spray dried lactose in said composition is the preponderant excipient (not less than 70% of the final composition.)
  • U.S. Pat. No. 5,258,185 describes rapidly absorbable formulations of glyburide prepared by dissolving the drug in liquid polyethylene glycol and/or an alcohol (e.g., ethanol) with a sugar alcohol (e.g., sorbitol) solution and optionally an alkalizing agent (e.g., ammonia). This solution is blended with suitable powdered pharmaceutically acceptable excipients to provide a dry granulation material suitable for compression into tablets. Similarly, Ganley ([0007] J. Pharm. Pharmac., 36:734-739, 1984) describes an improved formulation of glyburide by including solid polyethylene glycol in a capsule formulation, and Shaheen (Int. J. Pharm., 38:123-131, 1987) uses polyethylene glycol and an alkalizing agent, tromethamine, to provide for rapid glyburide release from a tablet formulation.
  • Because of the poor water solubility of glyburide, the rate of dissolution of the drug from a dosage form is a controlling factor in determining the rate and extent of drug absorption. The rate of dissolution depends on particle size (or particle surface area, which can be related to particle size). Borchert ([0008] Pharmazie, 31:307-309,1976) demonstrated the importance of this in vivo where studies in rats and dogs showed more extensive absorption of glyburide when a fine particle size material was evaluated against a coarser material, the drug being administered as a suspension. Arnqvist et al (Ann. Clin. Res., 15: 21-25, 1983) showed it was possible to micronize glyburide to such an extent that the reduced particle size of glyburide provided, relative to the reference formulation, higher maximum serum concentrations and greater area under the serum concentration time curve after dosing a tablet containing a reduced amount of drug.
  • None of these studies however show how to define properly the limits of particle size properties required in order to provide for appropriate bioavailability from a solid dosage form containing glyburide. It has been found that the appropriate bioavailability for glyburide is obtained when the particle size reduction of the glyburide is controlled so as not to provide what is classically accepted as “micronized” material, yet is fine enough to provide for the desired rate of dissolution. Also helpful for obtaining the appropriate bioavailability is the choice of excipients used in the formulation. The preferred excipients, known in the art, would be those that allow drug release to occur without substantially influencing the rate of drug dissolution and hence absorption. Such excipients would be highly soluble in water, and hence dissolve rapidly when the dosage form is immersed in an aqueous environment. In this way, the poorly soluble glyburide is liberated as a finely divided suspension. Dissolution of glyburide from this suspension, the rate of which is controlled by the particle size distribution of the suspension, is a prerequisite for absorption. Hence, the absorption characteristics are defined by the particle size distribution of the glyburide. In this way, as modeled by in vitro testing, the preferred dosage form is rapidly converted to a suspension of glyburide particles when the dosage form is ingested. Poorly soluble excipients may result in a dosage form that erodes too slowly. For example, dosage forms prepared with the insoluble excipient dicalcium phospate show slow erosion and consequently slow liberation of glyburide. Some currently marketed glyburide formulations, for example Micronase™, employ such excipients, and as a result can exhibit relatively slow liberation of glyburide into solution. Tablets and capsules prepared according to the current invention using soluble excipients released 80% of their contained glyburide within 20 minutes in a medium of pH 6.4 phosphate buffer with 1% w/w sodium dodecyl sulphate medium and agitation conditions of paddles at 50 rpm. [0009]
  • The appropriate bioavailability of glyburide avoids rapidly achieving a very high maximum (“spiked”) drug concentration in blood plasma. A very high concentration can predispose the patient to undesirable hypoglycemia. Additionally, the appropriate bioavailability of glyburide provides for the adequate extent of drug absorption such that an area under the plasma drug concentration against time curve maintains efficacy. While not being bound by any theory, it appears that it is this combination, i.e., the early onset of glyburide absorption, without producing excessively high maximum plasma drug concentrations, yet also maintaining exposure of the patient to the drug, that permits the glyburide of this invention to be employed as an oral preprandial secretagogue. [0010]
  • Other drug substances may be co-formulated with glyburide as well and still allow for appropriate glyburide bioavailability. In particular, combination tablets or capsules for multiple drug therapy of diabetes is contemplated. [0011]
  • Data from studies with metformin hydrochloride/glyburide tablets formulated with glyburide of different particle size characteristics allowed for the development of a correlation between glyburide particle size and the in vivo performance. The properties of the lots of glyburide used in the series of combination tablets employed are shown in the table below. The desired particle size distribution may be obtained by sieving or, preferably, air jet milling, and was measured by a laser light scattering method. [0012]
    Glyburide particle size (microns)
    Tablet batch 25% undersize 50% undersize 75% undersize
    Combo 1 15 33 62
    Combo 2 28 58 88
    Combo 3 10 25 52
    Combo 4  6 11 19
  • When four compositionally-identical individual batches of tablets of metformin hydrochloride-glyburide 500/2.5 mg were prepared using each of these lots of glyburide and dosed to humans, the following pharmacokinetic parameters were found on analysis of the glyburide plasma concentration-time curves: [0013]
    Pharmacokinetic parameters, glyburide
    AUC Cmax AUC
    Cmax (ng/ml, (ng/ml/hr, (ng/ml, (ng/ml/hr,
    Tablet batch geo. mean) geo. mean) arith. mean) arith. mean)
    Combo 1 71 478 76 493
    Combo 2 52 345 54 339
    Combo 3 64 513 67 531
    Combo 4 88 642 93 716
  • A reasonable correlation can be obtained between the particle size and the maximum attained geometric mean glyburide plasma concentration, Cmax, and also the geometric mean area under the glyburide plasma concentration-time curve, AUC. [0014]
  • From these correlations, projected limits on particle size for glyburide that would give predicted Cmax and AUC values ±25% of a mean value for batches of the reference glyburide formulation, Micronase™, utilized in the in vivo studies were calculated. [0015]
  • Accommodating both Cmax and AUC requirements, the projected particle size limits then become: [0016]
    25% undersize limits 50% undersize limits 75% undersize limits
    3-11 microns 6-23 microns 15-46 microns
  • The particle size measurement method of laser light scattering uses drug substance dispersed in liquid paraffin for introduction into the measurement cell. The apparatus produces a volume based, cumulative size distribution. Based on the above data and this methodology, it was found that the preferred particle sizes for glyburide to assure reproducibility of dissolution and bioavailability are: [0017]
  • 25% undersize value between 4 and 7 microns, [0018]
  • 50% undersize value between 7 and 13 microns, and [0019]
  • 75% undersize value between 17 and 23 microns. [0020]
  • Particularly preferred particle sizes for glyburide are: [0021]
  • 25% undersize value not more than 6 microns, [0022]
  • 50% undersize value not more than 7 to 10 microns, and [0023]
  • 75% undersize value not more than 21 microns. [0024]
  • These limits can thus be placed on the glyburide to assure reproducibility and appropriate bioavailability each time the drug substance is prepared and used in tablet or capsule formulation. [0025]
  • Glyburide having these particle size characteristics have powder surface area values in the range of about 1.7 to 2.2 m[0026] 2g−1 as determined by nitrogen adsorption. This is yet another difference between the glyburide of the invention and that of the prior art. The glyburide of the prior art generally required its powder surface area to be in excess of 3 m2g−1 (preferably 5 to 10 m2g−1) to yield appropriate glyburide bioavailability. The glyburide of particle size properties detailed herein produces appropriate glyburide bioavailability in humans.
  • When formulating the glyburide into a tablet or capsule, it is preferable to include in the formulation a suitable level of highly water-soluble excipients. Such excipients are generally soluble in water from 50 mg/ml to in excess of 300 mg/ml. They can be used singly or in combination and may comprise 45 to 90% by weight of the total formulation. Such a material used in a tablet or capsule formulation will completely dissolve within 5 to 30 minutes when subjected to an in vitro drug release test procedure, liberating the suspension of glyburide particles. The formulation may also include a binder such as povidone or low viscosity hydroxypropyl methylcellulose and a lubricant, such as magnesium stearate or sodium stearyl fumarate. The inclusion of a disintegrant has been found to be highly desirable to assure the rapid break up of the dosage form when immersed in an aqueous environment. Suitable disintegrants include croscarmellose sodium or sodium starch glycollate. The formulation may optionally include other excipients such as glidants, anti-adherents, colors, flavors, film coating components (including polymers such as hydroxypropyl methylcellulose, wetting agents such as polysorbate 20, plasticizers such as polyethylene glycol 200), and other materials commonly used in the formulation of tablets and capsules and as would be familiar to those skilled in the art. [0027]
  • Suitable highly water soluble excipients would also include, but not be limited to, sugar alcohols such as mannitol, sorbitol and xylitol; sugars such as sucrose, lactose, maltose and glucose; oligosaccharides such as maltodextrins. [0028]
  • EXAMPLE 1 Glyburide
  • Bulk glyburide was introduced into an air jet mill (Esco Strahlmuehle) via a hopper equipped with a screw feed, and the speed of charge was set at 20 to 30 kg/hour. The mill was operated with a Venturi nitrogen pressure of approximately 1.5 atmospheres and a micronization chamber pressure of 4 atmospheres. Size reduction was not allowed to proceed to the extent normally employed to make glyburide that would be described as micronized. The mill was turned off and the drug substance was discharged from it. A sample of the size-reduced glyburide was evaluated by a laser diffraction particle size analysis method. The following results were obtained: [0029]
  • D25% 5 microns, D50% 9 microns, D75% 21 microns [0030]
  • (Note: Such a size reduction process in the mill normally would be allowed to proceed to produce typical micronized material of commerce. A commercially available micronized sample was tested by the particle size analysis method and the following results obtained: [0031]
  • D25% 2.8 microns, D50% 4.5 microns, D75% 7.3 microns. [0032]
  • Hence the material of this Example is different from the commercially available micronized glyburide sample tested.) [0033]
  • EXAMPLE 2
  • The following single entity glyburide formulation was prepared. [0034]
    Ingredient mg per Tablet
    Mannitol 150.0
    Glyburide of Example 1 5.0
    Croscarmellose sodium 6.25
    Microcrystalline cellulose 75.0
    Povidone 12.5
    Magnesium stearate 0.2-2.5
  • The glyburide was blended with the croscarmellose sodium and that mixture was blended with the mannitol. The resulting blend was wet granulated using the povidone dissolved in an appropriate amount of purified water. The granules obtained were dried to an appropriate residual moisture content, mixed with the microcrystalline cellulose, lubricated by mixing with the magnesium stearate and compressed into tablets each containing 5 mg of glyburide. [0035]
  • The tablets were subjected to an in vitro dissolution method to determine the rate at which the glyburide was released from the tablets. The tablets were placed into a dissolution medium of pH 6.4 phosphate buffer with 1% w/w sodium dodecyl sulphate, and stirred with paddles at 50 rpm. It was found that 80% of the drug in the tablet was dissolved within 20 minutes. [0036]
  • EXAMPLE 3
  • [0037]
    Ingredient mg. per Tablet
    Mannitol 250.0
    Glyburide of Example 1 1.25
    Croscarmellose sodium 7.0
    Microcrystalline cellulose 28.25
    Povidone 10.0
    Magnesium stearate 0.6-6.0 
    Film coat (optional) 4.5-12.0
  • A process similar to the process described in Example 2 would yield tablets containing 1.25 mg of glyburide. The tablets are optionally film coated with a proprietary film coat composition such as OPADRY, employing a side vented coating pan. [0038]
  • EXAMPLE 4
  • [0039]
    Ingredient mg per tablet
    Lactose monohydrate 250.0
    Glyburide of example 1 5.0
    Croscarmellose sodium 7.0
    Microcrystalline cellulose 28.25
    Povidone 10.0
    Magnesium stearate 0.6-6.0
  • A process similar to the process described in Example 2 yielded tablets containing 5.0 mg of glyburide. [0040]
  • EXAMPLE 5
  • The glyburide of the invention can be co-formulated with other drugs for the treatment of type II diabetes. This would facilitate treatment for patients having to take multiple medications when single drug therapy is inadequate to control their disease. Such agents might include, but would not be limited to, acarbose or other glycosidase inhibitors, rosiglitazone, pioglitazone or other thiazolidonediones, biguanides such as metformin fumarate, repaglinide and other “aglinides”. [0041]
  • Example with Rosiglitazone Maleate
  • [0042]
    Ingredient mg. per Tablet
    Mannitol 250.0
    Rosiglitazone maleate 2.65
    Glyburide of Example 1 1.25
    Croscarmellose sodium 7.0
    Microcrystalline cellulose 28.25
    Povidone 10.0
    Magnesium stearate 0.6-6.0
  • By a process similar to the process described in Example 2, the two drug substances are first blended with the croscarmellose sodium and the remaining ingredients are then added to provide tablets, each containing 1.25 mg of glyburide and 2 mg of rosiglitazone (as the maleate salt). [0043]
  • Those of ordinary skill in the art will appreciate that the embodiments shown can be modified without departing from the spirit and scope of the invention. [0044]

Claims (10)

What is claimed is:
1. The substance 5-chloro-N-[2-[4-[[[(cyclohexylamino)-carbonyl]amino]sulfonyl]phenyl]ethyl]-2-methoxybenzamide having the following particle size distribution characteristics:
25% undersize value between 3 and 11 μm,
50% undersize value between 6 and 23 μm, and
75% undersize value between 15 and 46 μm.
2. The substance of
claim 1
wherein the particle size distribution is
25% undersize value between 4 and 7 μm,
50% undersize value between 7 and 13 μm, and 75% undersize value between 17 and 23 μm.
3. The use of the substance of
claim 1
in a tablet or capsule.
4. A tablet or capsule comprising the substance of
claim 1
and a second drug, the second drug being a drug that is useful for the treatment of type II diabetes.
5. The tablet or capsule of
claim 4
wherein the second drug is selected from the group consisting of glycosidase inhibitors, thiazolidonediones, biguanides and aglinides.
6. The tablet or capsule of
claim 5
wherein the second drug is selected from the group consisting of acarbose, rosiglitazone, pioglitazone, metformin fumarate and repaglinide.
7. A tablet or capsule comprising the substance of
claim 1
and at least one highly water soluble excipient.
8. The tablet or capsule of
claim 7
wherein the at least one highly water soluble excipient comprises 45 to 90% by weight of the total formulation.
9. A method of treating type II diabetes which comprises administering to a patient in need of such treatment a therapeutically effective amount of the substance of
claim 1
.
10. The substance 5-chloro-N-[2-[4-[[[(cyclohexylamino)-carbonyl]amino]sulfonyl]phenyl]ethyl]-2-methoxybenzamide having the following particle size distribution characteristics:
25% undersize value not more than 6 microns,
50% undersize value not more than 7 to 10 microns, and
75% undersize value not more than 21 microns.
US09/735,334 2000-01-14 2000-12-11 Glyburide composition Abandoned US20010036479A1 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
US48370300A true 2000-01-14 2000-01-14
US09/735,334 US20010036479A1 (en) 2000-01-14 2000-12-11 Glyburide composition

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US09/735,334 US20010036479A1 (en) 2000-01-14 2000-12-11 Glyburide composition
US10/426,211 US6830760B2 (en) 2000-01-14 2003-04-30 Glyburide composition

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
US48370300A Continuation-In-Part 2000-01-14 2000-01-14

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US10/426,211 Continuation US6830760B2 (en) 2000-01-14 2003-04-30 Glyburide composition

Publications (1)

Publication Number Publication Date
US20010036479A1 true US20010036479A1 (en) 2001-11-01

Family

ID=23921174

Family Applications (2)

Application Number Title Priority Date Filing Date
US09/735,334 Abandoned US20010036479A1 (en) 2000-01-14 2000-12-11 Glyburide composition
US10/426,211 Active 2020-02-24 US6830760B2 (en) 2000-01-14 2003-04-30 Glyburide composition

Family Applications After (1)

Application Number Title Priority Date Filing Date
US10/426,211 Active 2020-02-24 US6830760B2 (en) 2000-01-14 2003-04-30 Glyburide composition

Country Status (36)

Country Link
US (2) US20010036479A1 (en)
EP (1) EP1250321B1 (en)
JP (1) JP4787446B2 (en)
CN (1) CN1210258C (en)
AR (1) AR031547A1 (en)
AT (1) AT330937T (en)
AU (1) AU771705B2 (en)
BG (1) BG65782B1 (en)
BR (1) BR0107564A (en)
CA (1) CA2397294C (en)
CZ (1) CZ20022429A3 (en)
DE (1) DE60120916T2 (en)
DK (1) DK1250321T3 (en)
EE (1) EE05020B1 (en)
ES (1) ES2264967T3 (en)
GE (1) GEP20043299B (en)
HU (1) HU228825B1 (en)
IL (2) IL150383D0 (en)
LT (1) LT5024B (en)
LV (1) LV12914B (en)
MX (1) MXPA02006835A (en)
MY (1) MY128577A (en)
NO (1) NO328152B1 (en)
NZ (1) NZ519920A (en)
PL (1) PL356210A1 (en)
PT (1) PT1250321E (en)
RO (1) RO121381B1 (en)
RU (1) RU2244707C2 (en)
SK (1) SK286925B6 (en)
TN (1) TNSN01005A1 (en)
TR (1) TR200201798T2 (en)
TW (1) TWI287989B (en)
UA (1) UA73968C2 (en)
UY (1) UY26529A1 (en)
WO (1) WO2001051463A1 (en)
ZA (1) ZA200205528B (en)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007131930A1 (en) * 2006-05-13 2007-11-22 Novo Nordisk A/S Tablet formulation comprising repaglinide and metformin
US8911781B2 (en) 2002-06-17 2014-12-16 Inventia Healthcare Private Limited Process of manufacture of novel drug delivery system: multilayer tablet composition of thiazolidinedione and biguanides

Families Citing this family (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050271737A1 (en) * 2001-06-07 2005-12-08 Chinea Vanessa I Application of a bioactive agent to a substrate
US7767249B2 (en) * 2001-06-07 2010-08-03 Hewlett-Packard Development Company, L.P. Preparation of nanoparticles
WO2003080056A2 (en) * 2002-03-21 2003-10-02 Teva Pharmaceutical Industries Ltd. Fine particle size pioglitazone
CN1874774B (en) 2003-10-31 2011-04-13 武田药品工业株式会社 Solid preparation comprising an insulin sensitizer, an insulin secretagogue and a polyoxyethylene sorbitan fatty acid ester
AU2004318976B2 (en) * 2004-04-29 2009-04-09 Lotus Pharmaceutical Co., Ltd. Oral modified-release lozenges and their preparation method
CN100455279C (en) 2004-04-29 2009-01-28 美时化学制药股份有限公司 Oral administered sustained release lozenge composition and its preparation method
WO2006109175A2 (en) * 2005-04-11 2006-10-19 Aurobindo Pharma Limited Solid dosage form of an antidiabetic drug
US8529537B2 (en) * 2005-08-05 2013-09-10 Kimberly-Clark Worldwide, Inc. Absorbent article with enclosures
CN101287467B (en) 2005-08-22 2011-01-19 梅里奥尔医药I公司 Methods and formulations for modulating Lyn kinase activity and treating related disorders
KR101452518B1 (en) 2005-08-22 2014-10-21 멜리어 파마슈티칼스 아이, 인코포레이티드 Methods and formulations for modulating lyn kinase activity and treating related disorders
TW200816995A (en) * 2006-08-31 2008-04-16 Daiichi Sankyo Co Ltd Pharmaceutical composition containing insulin sensitizers
EP1967182A1 (en) * 2007-03-07 2008-09-10 KRKA, tovarna zdravil, d.d., Novo mesto Pharmaceutical composition comprising a salt of rosigliatazone
US8552184B2 (en) 2008-07-03 2013-10-08 Melior Pharmaceuticals I, Inc. Compounds and methods for treating disorders related to glucose metabolism
WO2010048287A2 (en) 2008-10-22 2010-04-29 University Of Pittsburgh-Of The Commonwealth System Of Higher Education Radioprotective agents
EP2520298A1 (en) 2011-05-03 2012-11-07 Assistance Publique, Hopitaux De Paris Pharmaceutical composition comprising sulfonylureas (glibenclamide) or meglitinides for use for treating hyperglycaemia or for promoting growth of a premature infant
CN102743354A (en) * 2012-07-31 2012-10-24 南京正科制药有限公司 Repaglinide tablet and preparation method thereof
CN103142521B (en) * 2013-03-21 2014-06-25 西南药业股份有限公司 Glibenclamide tablet and preparation method thereof
CN104127423A (en) * 2014-07-30 2014-11-05 沈阳药科大学 Gliquidone derivative, preparation method and application thereof
CN104127424A (en) * 2014-07-30 2014-11-05 沈阳药科大学 Glibenclamide derivative, preparation method and application thereof

Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3174901A (en) * 1963-01-31 1965-03-23 Jan Marcel Didier Aron Samuel Process for the oral treatment of diabetes
US3979520A (en) * 1973-09-26 1976-09-07 Boehringer Mannheim G.M.B.H. Preparation of rapidly resorbable glibenclamide
US4060634A (en) * 1973-09-26 1977-11-29 Boehringer Mannheim G.M.B.H. Rapidly resorbable glibenclamide
US4916163A (en) * 1985-06-04 1990-04-10 The Upjohn Company Spray-dried lactose formulation of micronized glyburide
US5631224A (en) * 1992-03-19 1997-05-20 Novo Nordisk A/S Use of a peptide
US5663198A (en) * 1993-07-15 1997-09-02 Hoechst Aktiengesellschaft Drug formulations comprising coated, very sparingly water-soluble drugs for inhalational pharmaceutical forms, and process for their preparation
US5922769A (en) * 1995-11-14 1999-07-13 Abiogen Pharma S.R.L. Glibenclamide-metformin combination for the treatment of diabetes mellitus of type II
US5932245A (en) * 1991-12-05 1999-08-03 Alfatec Pharma Gmbh Gelatin or collagen hydrolysate containing drug formulation that provides for immediate release of nanoparticle drug compounds
US5965584A (en) * 1995-06-20 1999-10-12 Takeda Chemical Industries, Ltd. Pharmaceutical composition
US6153632A (en) * 1997-02-24 2000-11-28 Rieveley; Robert B. Method and composition for the treatment of diabetes

Family Cites Families (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE1185180B (en) 1963-10-19 1965-01-14 Hoechst Ag A process for preparing benzenesulfonylureas
US3454635A (en) 1965-07-27 1969-07-08 Hoechst Ag Benzenesulfonyl-ureas and process for their manufacture
CA889876A (en) 1970-09-10 1972-01-04 Frank W. Horner Limited Purification of glyburide
DE3833439A1 (en) 1988-10-01 1991-09-12 Hoechst Ag A process for the micronisation of glibenclamide
DE68907062D1 (en) 1988-10-05 1993-07-15 Upjohn Co The finely divided solid crystalline powder by precipitation in an anti-spoon medium.
US5258185A (en) 1989-08-23 1993-11-02 Bauer Kurt H Highly active, rapidly absorbable formulations of glibenclamide, processes for the production thereof and their use
DE19721467A1 (en) * 1997-05-22 1998-11-26 Basf Ag A process for preparing small-scale preparations of biologically active substances
EP0996444B1 (en) 1997-06-18 2007-03-07 SmithKline Beecham plc Treatment of diabetes with thiazolidinedione and metformin
GB9715306D0 (en) 1997-07-18 1997-09-24 Smithkline Beecham Plc Novel method of treatment
ES2191977T3 (en) * 1997-10-27 2003-09-16 Merck Patent Gmbh Solutions and dispersions of solid state drugs poorly soluble in water.
PT974356E (en) 1998-07-15 2004-02-27 Merck Sante Sas Tablets comprising a combination of metformin and glibenclamide
US7374779B2 (en) * 1999-02-26 2008-05-20 Lipocine, Inc. Pharmaceutical formulations and systems for improved absorption and multistage release of active agents
US6294192B1 (en) * 1999-02-26 2001-09-25 Lipocine, Inc. Triglyceride-free compositions and methods for improved delivery of hydrophobic therapeutic agents

Patent Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3174901A (en) * 1963-01-31 1965-03-23 Jan Marcel Didier Aron Samuel Process for the oral treatment of diabetes
US3979520A (en) * 1973-09-26 1976-09-07 Boehringer Mannheim G.M.B.H. Preparation of rapidly resorbable glibenclamide
US4060634A (en) * 1973-09-26 1977-11-29 Boehringer Mannheim G.M.B.H. Rapidly resorbable glibenclamide
US4916163A (en) * 1985-06-04 1990-04-10 The Upjohn Company Spray-dried lactose formulation of micronized glyburide
US5932245A (en) * 1991-12-05 1999-08-03 Alfatec Pharma Gmbh Gelatin or collagen hydrolysate containing drug formulation that provides for immediate release of nanoparticle drug compounds
US5631224A (en) * 1992-03-19 1997-05-20 Novo Nordisk A/S Use of a peptide
US5663198A (en) * 1993-07-15 1997-09-02 Hoechst Aktiengesellschaft Drug formulations comprising coated, very sparingly water-soluble drugs for inhalational pharmaceutical forms, and process for their preparation
US5965584A (en) * 1995-06-20 1999-10-12 Takeda Chemical Industries, Ltd. Pharmaceutical composition
US5922769A (en) * 1995-11-14 1999-07-13 Abiogen Pharma S.R.L. Glibenclamide-metformin combination for the treatment of diabetes mellitus of type II
US6153632A (en) * 1997-02-24 2000-11-28 Rieveley; Robert B. Method and composition for the treatment of diabetes

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8911781B2 (en) 2002-06-17 2014-12-16 Inventia Healthcare Private Limited Process of manufacture of novel drug delivery system: multilayer tablet composition of thiazolidinedione and biguanides
WO2007131930A1 (en) * 2006-05-13 2007-11-22 Novo Nordisk A/S Tablet formulation comprising repaglinide and metformin
US20090252790A1 (en) * 2006-05-13 2009-10-08 Novo Nordisk A/S Tablet formulation

Also Published As

Publication number Publication date
IL150383D0 (en) 2002-12-01
JP4787446B2 (en) 2011-10-05
DE60120916T2 (en) 2007-02-15
SK9832002A3 (en) 2003-07-01
CN1210258C (en) 2005-07-13
ZA200205528B (en) 2003-10-10
TWI287989B (en) 2007-10-11
AR031547A1 (en) 2003-09-24
JP2003519681A (en) 2003-06-24
TR200201798T2 (en) 2002-11-21
DK1250321T3 (en) 2006-07-31
MXPA02006835A (en) 2003-01-28
BG106870A (en) 2003-03-31
TNSN01005A1 (en) 2005-11-10
IL150383A (en) 2007-03-08
AU771705B2 (en) 2004-04-01
AT330937T (en) 2006-07-15
DE60120916D1 (en) 2006-08-03
UA73968C2 (en) 2002-10-15
EP1250321A1 (en) 2002-10-23
PL356210A1 (en) 2004-06-14
LV12914B (en) 2003-01-20
CA2397294C (en) 2011-03-22
AU2474001A (en) 2001-07-24
NO20023367D0 (en) 2002-07-12
LT2002085A (en) 2003-01-27
PT1250321E (en) 2006-09-29
BG65782B1 (en) 2009-11-30
CN1395560A (en) 2003-02-05
EE200200393A (en) 2003-10-15
EP1250321B1 (en) 2006-06-21
CZ20022429A3 (en) 2003-06-18
CA2397294A1 (en) 2001-07-19
WO2001051463A1 (en) 2001-07-19
HU0203852A2 (en) 2003-04-28
NO328152B1 (en) 2009-12-21
RU2244707C2 (en) 2005-01-20
RU2002121626A (en) 2004-01-10
RO121381B1 (en) 2007-04-30
LT5024B (en) 2003-06-25
NO20023367L (en) 2002-09-04
MY128577A (en) 2007-02-28
EE05020B1 (en) 2008-06-16
HU0203852A3 (en) 2005-05-30
US6830760B2 (en) 2004-12-14
NZ519920A (en) 2004-06-25
US20030185880A1 (en) 2003-10-02
BR0107564A (en) 2002-10-01
UY26529A1 (en) 2001-08-27
ES2264967T3 (en) 2007-02-01
GEP20043299B (en) 2004-03-10
HU228825B1 (en) 2013-05-28
SK286925B6 (en) 2009-07-06

Similar Documents

Publication Publication Date Title
AU2006297444B2 (en) Formulation comprising metformin and vildagli ptin
US4443428A (en) Extended action controlled release compositions
KR101406767B1 (en) Extended release tablet formulation containing pramipexole or a pharmaceutically acceptable salt thereof, method for manufacturing the same and use thereof
US6503911B2 (en) Sustained release ranolazine formulations
AU737738B2 (en) Pharmaceutical preparation comprising clodronate as active ingredient and silicified microcrystalline cellulose as excipient
EP0665744B1 (en) Stable extended release oral dosage composition
JP4969338B2 (en) Solid oral dosage forms of valsartan
ES2536514T3 (en) Pharmaceutical Compositions based dual action antagonist superstructures / angiotensin receptor blocker (ARB) and receiver neutral endopeptidase (NEP)
US9339472B2 (en) Coated tablet formulation and method
RU2335280C2 (en) Tablets of tamsulosin with modified release
EP3395338B1 (en) Rapid dissolution formulation of cinacalcet hcl
US6238695B1 (en) Formulation of fast-dissolving efavirenz capsules or tablets using super-disintegrants
KR100350940B1 (en) Stabilized pharmaceutical composition containing bupropion
US4454108A (en) Prolonged-action multiple-layer tablets
EP0693281B1 (en) Fluoxetine Pharmaceutical formulations
US6936274B2 (en) Storage stable thyroxine active drug formulations and methods for their production
EP1327440B1 (en) Oral preparations with favorable disintegration characteristics
ES2363127T3 (en) Pharmaceutical compositions containing irbesartan and diuretic.
AU759018B2 (en) Compressed nitroglycerin tablet and its method of manufacture
US20020054911A1 (en) Novel oral dosage form for carvedilol
US6333332B1 (en) Stabilized pharmaceutical compositions containing bupropion hydrochloride
JP4108980B2 (en) The sustained release ranolazine formulations
US20110206827A1 (en) Film-coated tablet or granules containing as active ingredient a pyridylpyrimidine compound or a pharmaceutically acceptable salt of this compound
CA2474674C (en) Solid preparation containing single crystal form
KR100765580B1 (en) Deferacirox dispersible tablets

Legal Events

Date Code Title Description
AS Assignment

Owner name: BRISTOL-MYERS SQUIBB COMPANY, NEW JERSEY

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:CAVE, GILLIAN;NICHOLSON, SARAH J.;REEL/FRAME:011780/0602

Effective date: 20010424

STCB Information on status: application discontinuation

Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION