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Granulate containing a pharmaceutically active substance and method for its manufacture

A technology of drug activity and emulsifier, which is applied in the direction of pharmaceutical formulation, drug combination, drug delivery, etc., can solve the problems of poor dispersion and achieve rapid absorption

Active Publication Date: 2009-12-02
艾可制药有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Especially in the case of pharmaceutically active substances that are substantially insoluble or poorly dispersible in water, the main challenge is to formulate the active substance in the mucosa in such a way that it can be effectively absorbed by the mucosal tissue. Rapid release delivery system in fluid

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0113] Sucrose monolaurate (HLB=15) and tetrahydrocannabinol (THC) were heated to 120°C under nitrogen flow. The ratio of THC to sucrose monolaurate was 1:15 (by weight). After mixing thoroughly, use either of the following methods to 2 To saturate (and thus soften) a putty-like melt:

[0114] • Pour the warm melt into an autoclave preheated to 120°C and pressurize to 250 bar. The autoclave was pressurized with carbon dioxide using a plunger pump (LeWa) and heated with heating oil through the jacket. By utilizing Büchi TM Magnetic stirrer in supercritical CO 2 Stir the melt for at least 30 minutes in CO 2 Saturation takes place, whereby the lump is further liquefied.

[0115] • Cool the melt to -20°C and crush to obtain maximum surface area. For this, use a mortar precooled to -20 °C in an inert dry atmosphere. The resulting powder was poured into an autoclave preheated to 60° C. and pressurized to 250 bar. The autoclave was pressurized with carbon dioxide using a plu...

Embodiment 2

[0118] THC was dissolved in a 65% (w / v) solution of sucrose monolaurate in 2-propanol to a final concentration of 7.3% (w / v). The high pressure vessel was pressurized to 200 bar with carbon dioxide by a plunger pump (Williams) and heated to 40°C with heating oil through the jacket.

[0119] The solution was sprayed into the container by a syringe pump (ISCO 260D) through a coaxial nozzle. The nozzle consists of two concentric tubes; 25 ml / min of emulsion is fed through the inner tube (inner diameter = 0.5 mm, outer diameter = 1.27 mm) and 500 g / min of carbon dioxide is fed through the outer tube (inner diameter = 1.7 mm). The carbon dioxide was heated to 60°C before nebulization. The powder formed in the container was collected on a filter at the bottom of the container. The microparticles have an average diameter measured by S.E.M. of 5-50 μm.

Embodiment 3

[0121] Dilute water with sucrose stearate (Crodesta TM F-160; HLB=15) mixed. The mixture was heated to 60 °C and the Ultraturrax TM The blender disperses the molten THC into this mixture until a stable emulsion forms. The resulting oil-in-water emulsion contained 10 wt.% THC, 30 wt.% sucrose stearate and 60 wt.% water. The autoclave was heated to 40°C with heating oil through the jacket.

[0122] Using CO 2 The autoclave was pressurized to 30 bar and the solution was sprayed into the vessel through two fluid nozzles using a syringe pump (ISCO 260D). This nozzle consists of two concentric tubes; 0.3 ml / min of emulsion is fed through the inner tube (inner diameter = 0.5 mm, outer diameter = 1.27 mm) and 500 g / min of carbon dioxide is fed through the outer tube (inner diameter = 1.7 mm). Carbon dioxide was heated to 40°C before nebulization. The powder formed in the container was collected on a filter at the bottom of the container. The microparticles have an average diam...

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Abstract

One aspect of the present invention relates to a granulate having a volume weighted mean diameter of 1-200 m and containing: at least 0.1 wt.% of a p harmaceutically active substance; at least 10 wt.% of emulsifier 0-89.9 wt.% of a water-dispersible saccharide; the combination of the pharmaceutically active substance, the emulsifier and the water-dispersible saccharide together represening at least 60 wt.% of the granulate; wherein the granulate is monophasic or wherein the granulate comprises a dispersed phase containing the pharmaceutically active substance, said dispersed phase having a volume weighted mean diameter of less than 300 nm. Another aspect of the invention relates to a process for the preparation of said granulate containing a pharmaceutically active substance, which process employs.

Description

technical field [0001] The present invention relates to granules comprising a pharmaceutically active substance and an emulsifier. The particles of the invention are especially suitable for use in dosage units for mucosal (eg buccal, sublingual, peroral, nasal, pulmonary, rectal, intrauterine or intravaginal) administration. [0002] The invention also provides a method for preparing the particles. Background technique [0003] In order for a pharmaceutical active to be delivered to exert systemic drug action, the pharmaceutical active must be absorbed into the bloodstream after administration. Especially if the drug substance is administered transmucosally, it is important that the drug active substance is released rapidly from the drug dosage unit into the aqueous environment in the vicinity of the mucosal tissue so that it can be absorbed by said mucosal tissue. Especially in the case of pharmaceutically active substances that are substantially insoluble or poorly dispe...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/00A61K9/16
CPCA61K9/2013A61K9/1694A61K9/2018A61K9/1617A61K9/2059A61K9/1623A61P43/00
Inventor 胡贝特·克莱门斯·佩利卡安彼得·塞巴斯蒂安·韦尔默朗约翰内斯·卡斯帕·马蒂亚斯·伊利莎白·本德马里亚·瓦内萨·费尔南德斯·奇德
Owner 艾可制药有限公司