Modified dosage forms of tacrolimus

A tacrolimus and release agent technology, applied in the field of regulated release tacrolimus formulations, can solve problems such as impact, incomplete absorption, and low bioavailability

Inactive Publication Date: 2010-02-17
PANACEA BIOTEC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] As mentioned above, the various concerns of tacrolimus treatment are complete metabolism, incomplete and variable absorption, low bioavailability, food influence and side effects

Method used

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  • Modified dosage forms of tacrolimus
  • Modified dosage forms of tacrolimus
  • Modified dosage forms of tacrolimus

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0103] According to the present invention, dosage forms are prepared which contain an immediate release component and a release modifying component. The procedure consisted of dissolving a hydrophilic surfactant (vitamin E TPGS), tacrolimus and a lipophilic surfactant (glycerol monooleate) in a suitable solvent (isopropanol) and coating a blank sphere core. These obtained pellets are divided into two parts, using suitable coating equipment, to form one part of the immediate release dosage unit, which is further coated with a film-forming polymer solution to form the second part of the delayed release dosage unit, using The compositions given in Table 1 were coated with enteric material. Pellets of the immediate and delayed release components corresponding to their required amounts are then filled into capsules. In some formulations, the second portion of the composition forming the delayed release dosage unit may be coated with the film coating composition prior to enteric co...

Embodiment 2

[0112] According to the present invention, dosage forms are prepared which contain an immediate release component and a release modifying component. The steps include dissolving a hydrophilic surfactant (sodium lauryl sulfate, sodium dioctyl sulfosuccinate), tacrolimus, a water-soluble carrier in a suitable solvent (ethanol, dichloromethane or a mixture thereof) and other excipients to obtain a clear solution. The solution obtained above was coated on blank pellet cores. These obtained pellets are divided into two parts, using suitable coating equipment, to form one part of the immediate release dosage unit, which is further coated with a film-forming polymer solution to form the second part of the delayed release dosage unit, using Composition given in Table 3, coated with enteric material. Pellets of the immediate and delayed release components corresponding to their required amounts are then filled into capsules. In some formulations, the second portion of the dosage for...

Embodiment 3

[0120] Embodiment 3: pharmacokinetic research:

[0121] (a) The study was designed in a small group of healthy human volunteers to evaluate the pharmacokinetic profile of single-dose oral administration of tacrolimus compositions E and J (one dose per day, 5 mg) of the present invention; 1 and T 2 , and compared it to the reference product (R), a conventional immediate-release product available (2.5mg, administered twice a day) compared.

[0122] Study Design: Open-label, randomized, fasting, single-dose pharmacokinetic study. Healthy human volunteers fasted overnight prior to dosing. Individual volunteers took the formulation with 250 ml of water. Collect pre-dose and after predetermined time intervals (post-dose 0.5, 1.0, 1.5, 2.0, 4.0, 8.0, 9.0, 10.0, 11.0, 12.0, 12.5, 13.0, 13.5, 14.0, 16.0, 20.0, 22.0, 24.0, 36.0 hours) of blood samples. Volunteers were given a standard diet during the study. Plasma analysis using validated analytical methods for determination of ...

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Abstract

The present invention provides a modified release dosage form of tacrolimus that releases two or more amount of tacrolimus upon oral administration, the first amount of tacrolimus releases from the immediate release dosage unit substantially immediately within 0-2 hours followed by a time interval ranging from about 1-10 hours during which substantially no amount of tacrolimus is released from thedosage form, after which a second amount of tacrolimus is released wherein said second amount is released from the delayed release dosage unit either immediately e.g. within 0-2 hours or over a period of time ranging from about 2-12 hours from its initial release from the delayed release dosage unit. The dosage form may further comprise additional amount of tacrolimus to provide additional pulseof tacrolimus. The dosage forms of tacrolimus exhibit improved bioavailability and reduced flux or fluctuation over existing composition of tacrolimus. A method of preparing the dosage forms is also described.

Description

field of invention [0001] The present invention relates to a modified release tacrolimus dosage form that exhibits improved bioavailability and reduced inter-individual variability in pharmacokinetics. Background of the invention [0002] Tacrolimus, known as FK-506, is a macrolide immunosuppressant produced by Streptomyces tsukubaensis. Tacrolimus is available in various dosage forms such as capsules, injections, and ointments. The traditional capsule dosage form is as It is sold commercially and is approved for the prevention of organ rejection in patients receiving allogeneic liver, kidney or heart transplants. The absorption of orally administered tacrolimus from the gastrointestinal tract is incomplete and variable. The absolute bioavailability of tacrolimus is usually 17±10% (N=26) in adult kidney transplant patients, 22±6% (N=17) in adult liver transplant patients, and 22±6% (N=17) in adult heart transplant patients. Usually 23±9% (N=11) and 18±5% (N=16) in healt...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/4745A61K9/22
CPCA61K9/5078A61K9/146A61K31/436A61K9/1676A61K9/5084A61P37/06A61K9/20A61K31/44
Inventor 阿马尔吉特·辛格塞尔伯吉特·辛格沙瓦南德·珀思利拉杰什·贾殷
Owner PANACEA BIOTEC
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