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Pharmaceutical compositions of posaconazole

a technology of posaconazole and composition, which is applied in the direction of pharmaceutical non-active ingredients, powder delivery, organic active ingredients, etc., can solve the problems of difficult to obtain optimal drug exposure and adequate food intake for patients, and achieve improved bioavailability, improved composition, and poor water solubility

Active Publication Date: 2020-07-30
SLAYBACK PHARMA LLC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The compositions provide consistent and improved bioavailability of azole anti-fungal drugs across both fed and fasted states, reducing variability in pharmacokinetic parameters and ensuring adequate drug exposure, even in patients who may have difficulty consuming food.

Problems solved by technology

However, when posaconazole dissolved in the gastric fluids reaches the environment of the intestines, which is less acidic (typically a pH of about 6.4), a substantial amount of the dissolved posaconazole precipitates, hindering absorption in the intestines.
However, commercially available posaconazole delayed-release tablets (NOXAFIL®) are only prescribed for use with food because of relatively poor bioavailability when administered under fasted conditions.
Adequate food intake to obtain optimal drug exposure may be difficult for these patients.

Method used

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  • Pharmaceutical compositions of posaconazole
  • Pharmaceutical compositions of posaconazole
  • Pharmaceutical compositions of posaconazole

Examples

Experimental program
Comparison scheme
Effect test

examples

[0117]The following examples are provided for illustrative purpose only and should not be considered as limiting the scope of present invention in any way.

example 1

[0123]

TABLE 3Preparation of Posaconazole delayed release tabletsS. No.Name of MaterialUnit Qty (mg / tablet)Extrudate1Posaconazole1002Hypromellose acetate succinate3003Hydroxypropyl cellulose20Extra-granular Inactive Ingredients4Hydroxypropyl cellulose555Hypromellose acetate succinate256Microcrystalline cellulose597Croscarmellose sodium258Colloidal silicon dioxide39Magnesium stearate3Coating up to 3% w / w10Opadry II Yellow 85F52031717.711Water, purified@q.sTotal weight of coated tablet (mg)607.7q.s.—quantity sufficient

Manufacturing Procedure

[0124]Posaconazole, Hypromellose acetate succinate and Hydroxypropyl cellulose were weighed in the required quantities as shown in Table 3. The components were sifted and blended in a blender bin. The mixture was then fed to Zone 1 of a hot melt extruder. The hot melt extruder had temperature zones through which a twin screw conveys and kneads the solid and molten material, then finally extrudes molten mass through a die hole attached at the end. Th...

example 2

[0129]Dissolution profiles of Posaconazole DR tablets as prepared in example 1, comparative example were compared with commercially available NOXAFIL® DR tablets in 0.01N HCl acid media and followed by pH 6.5 Mcllvaine buffer with 0.126% Polysorbate 80.

[0130]When tested by using USP apparatus II (paddle); 500 ml of acid medium for 120 minutes and followed by 1000 ml of pH 6.5 Mcllvaine buffer with 0.126% Polysorbate 80 for 60 minutes at 37° C. and stirred at 75 RPM, the dissolution profile of Posaconazole DR tablets as prepared in example 1, comparative example and NOXAFIL® DR tablets are provided in the following table 5. Samples were withdrawn at 120 minutes in acid media and 5, 10, 15, 20, 30, 45- & 60-minutes time points in buffer media and analysed using HPLC system with UV detector at a wavelength 232 nm.

TABLE 5Time% drug releasedpointNOXAFIL ®ComparativeMedia(min)DR TabExampleExample 1Acid stage:120440.01N HClBuffer stage:5683927pH 6.510706653155373692044737730355978453039676...

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Abstract

Delayed-release pharmaceutical compositions prepared by hot-melt extrusion are provided, where the compositions comprise an azole anti-fungal drug having poor water solubility, an enteric polymer and a non-enteric polymer, and wherein the pharmaceutical composition may be orally administered to a patient in either the fed or fasted state. Preferably, the delayed-release pharmaceutical compositions prepared by hot-melt extrusion comprise posaconazole, HPMC-AS and HPC. Preferably, following oral administration of the pharmaceutical compositions, there is no substantial difference in the pharmacokinetic parameters (Tmax, Cmax, AUC0-t and / or AUC0-infinity) of the azole anti-fungal drug, regardless of whether the pharmaceutical compositions are administered to a subject in the fed or fasted state.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims foreign priority to Indian Application No. IN 201941003513, filed on Jan. 29, 2019, which is incorporated herein by reference in its entirety.FIELD OF THE INVENTION[0002]The present invention relates to delayed-release pharmaceutical compositions prepared by hot-melt extrusion, comprising an azole anti-fungal drug having poor water solubility, an enteric polymer and a non-enteric polymer, wherein the composition may be administered in either the fed or fasted state. In certain embodiments, the composition is a granulate material that can be filled into a capsule or can be compressed into a tablet.BACKGROUND OF THE INVENTION[0003]The present invention relates to delayed-release pharmaceutical compositions comprising an azole anti-fungal drug having poor water solubility, wherein the composition may be administered in either the fed or fasted state. Azole anti-fungal drugs having poor water solubility (e.g., includin...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K31/496A61P31/10A61K47/38A61K9/20
CPCA61K31/496A61K47/38A61K9/2095A61P31/10A61K9/146A61K9/2054A61K9/2077
Inventor JAIN, PARAS P.JAIN, GIRISH KUMAR
Owner SLAYBACK PHARMA LLC