Drug delivery systems comprising weakly basic drugs and organic acids

A weakly alkaline, organic acid technology, applied in drug delivery, drug combination, digestive system, etc., can solve problems such as the inability to maintain plasma distribution and dosing regimens

Inactive Publication Date: 2009-04-15
ADARE PHARM INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] Although moderately protracted drug release is possible in these published documents, these documents suffer from two disadvantages namely the inability to maintain sufficient plasma distribution to achieve a once-daily dosing regimen and the tendency towards complete in situ formation of the salt form. situ formation) thus forming new chemical entities

Method used

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  • Drug delivery systems comprising weakly basic drugs and organic acids
  • Drug delivery systems comprising weakly basic drugs and organic acids
  • Drug delivery systems comprising weakly basic drugs and organic acids

Examples

Experimental program
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Effect test

Embodiment approach

[0079] According to one embodiment of the present invention, the method may include the following steps:

[0080] a. Provide organic acid containing core particles (e.g. organic acid crystals with desired size distribution or particles comprising inert particles (e.g. sugar spheres, cellulose spheres, silica spheres) layered with polymer organic acids in the binder solution);

[0081] b. Core particles containing organic acids are coated with an SR coating film consisting of a single water-insoluble polymer (e.g. EC-10 (ethylcellulose with an average viscosity of 10 cps)) or a combination of a water insoluble polymer with a water soluble polymer such as povidone or PEG 400 or an enteric polymer such as hydroxypropylmethylcellulose phthalate (eg HP-55);

[0082] c. Coating a weakly basic drug layer on the SR-coated organic acid-containing core particles to form IR beads;

[0083] d. coating the barrier coating film on the IR beads with a solution of the water insoluble polyme...

Embodiment 1

[0110] A. Fumaric Acid SR Beads

[0111] 40-80 mesh fumaric acid crystals (3750 g) were loaded into a fluid bed coater Glatt GPCG 5 equipped with a 9" bottom spray Wurster insert, column length 10" and tubing 16 mm . 250g of ethyl cellulose (Ethocel Premium, 10cps, hereinafter referred to as EC-10) and 166.7g of polyethylene glycol (PEG 400) (the ratio of the two is 60 / 40) are dissolved in 98 / 2 acetone / water ( 6528.3 g), the resulting solution (6% solids concentration) was used to coat the above-mentioned acid crystals with a weight gain of up to 10% by weight. The treatment conditions are as follows: atomization air pressure is 2.0 bar; nozzle diameter is 1.00mm; bottom distribution plate is B; spray / shake interval is 30s / 3s; product temperature is maintained at 35±1°C; (inlet air volume) was 145-175 cubic feet per minute (cfm); and the spray rate was increased from about 8 g / min to 30 g / min.

[0112] In addition, fumaric acid crystals were coated with different ratios of ...

Embodiment 2

[0116] A. Cores containing fumaric acid

[0117] Hydroxypropyl cellulose (Klucel LF, 33.3 g) was slowly added to 90 / 10 denatured alcohol SD 3C 190 Proof (Denatured SD 3C 190 Proof Alcohol) (Denatured SD 3C 190 Proof Alcohol) (Water) at a solids concentration of 4% while stirring vigorously to dissolve, then slowly added Fumaric acid (300g) was dissolved. A Glatt GPCG 3 equipped with a 6" bottom spray Wurster insert and an 8" distribution column was packed with 866.7 g of 25-30 mesh sugar spheres. The sugar spheres were layered with the fumaric acid solution while maintaining a product temperature of about 33-34°C and maintaining an air inlet velocity of about 3.5-4.5 m / s. Dry the acid cores in the unit for 10 minutes to remove residual solvent / moisture, then pass through a 20-30 mesh screen.

[0118] B. SR coated fumaric acid core

[0119] Acid cores (1080 g) from above were prepared with 95 / 5 acetone / water solution (solid Concentration is 7.5%) carry out coating, weight g...

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Abstract

A pharmaceutical dosage form such as a capsule, a conventional or orally disintegrating tablet capable of delivering a nitrogen (N)-containing therapeutic agent having a pKa in the range of from about 5 to 14 into the body in a sustained- released fashion, in order to be suitable for a twice- or once-daily dosing regimen, comprises at least one organic acid, which solubilizes the therapeutic agent the drug prior to releasing it into the hostile intestinal environment wherein said weakly basic drug is practically insoluble. The unit dosage form is composed of a multitude of multicoated particulates (i.e., immediate-release beads, sustained- release beads and / or one or more timed, pulsatile-release bead populations) is designed in such a way that said weakly basic drug and said organic acid do not come into close contact during processing and / or storage for in-situ formation of acid addition compounds while ensuring that the acid is not depleted prior to completion of the drug release.

Description

[0001] Cross-References to Related Applications [0002] This application claims priority to US Provisional Application 60 / 762,766, filed January 27, 2006, the contents of which are incorporated herein by reference. technical field [0003] The present invention relates to the development of modified-release dosage forms comprising one or more timed, pulsatile-release bead populations comprising weak A basic nitrogen (N) therapeutic agent having a pK of about 5 to 14 and one or more pharmaceutically acceptable organic acids a and a solubility of not more than 200 μg / mL at pH 6.8. When dissolution was tested by the United States Pharmacopeia (USP) dissolution methodology using a two-stage dissolution medium (first in 0.1N HCl for two hours and then in pH 6.8 buffer), The dosage forms according to the invention show comparable release profiles of active and organic acid after a preset delay (lag-time). Another aspect of the present invention discloses the target PK (pharmacok...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/22
CPCA61K9/5078A61K9/5047A61K9/2077A61K9/0056A61K9/5084A61P1/08A61P25/08A61P25/18A61P7/02A61P9/10A61P9/12A61K9/20
Inventor 戈皮·M·文卡特施
Owner ADARE PHARM INC
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