Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Solubilized pharmaceutical composition for parenteral administration

A composition, parenteral technology, applied in the direction of drug combination, drug delivery, pharmaceutical formulation, etc.

Inactive Publication Date: 2002-11-27
LEO PHARMA PROD LTD AS LOVENS CHEM FAB PRODUKTIONS AS
View PDF0 Cites 3 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, parenteral administration of compositions containing Cremophor® EL was previously found to cause histamine release (Lorenz, W. et al., in Agents and Actions, 1982, 121 / 2, 64-80 and Ennis, M. et al., in Agents and Actions, 1985, 16 3 / 4, 265-268)
Anaphylaxis generated in humans after administration of drug dissolved in Cremophor@EL causes significant clinical problems

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Solubilized pharmaceutical composition for parenteral administration
  • Solubilized pharmaceutical composition for parenteral administration
  • Solubilized pharmaceutical composition for parenteral administration

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0148] Preparation of aqueous pharmaceutical compositions according to the invention

[0149] An aqueous solution for parenteral administration is prepared as follows Ingredients per ml (all are pharmacopoeia standards) Sescocalcitol (active substance) 10 μg disodium hydrogen phosphate dihydrate (buffer) 15.4 mg sodium dihydrogen phosphate dihydrate (buffer) 2 mg sodium chloride 0.8 mg sodium ascorbate (antioxidant) 5 mg BASF's Solutol® HS15 (solubilizer) 5 mg water for injection to 1 ml

[0150] Solutol(R) HS 15 is dissolved in water for injection by heating it to a temperature of up to 80°C. Nitrogen protection. Buffer substances and sodium chloride are added and the solution is cooled to not more than 30°C. Sodium ascorbate is then added and finally secocalcitol is dissolved in the resulting solution.

[0151] The solution is sterile filtered and autoclaved under appropriate time-temperature conditions.

Embodiment 2

[0153] Chemical Stability of Sescocalcitol in Aqueous Pharmaceutical Compositions

[0154] The chemical stability of secocalcitol in aqueous solution was studied in order to measure whether commonly used pharmaceutically acceptable excipients had any influence on the stability. The pH of this aqueous solution was adjusted to pH=7.5. Ascorbate present but no N 2 During protection, the pH value drops to 7.1-7.2 in a short time.

[0155]Sescocalcitol is a vitamin D analogue that is readily degraded in aqueous acidic environments. Thus, the degradation rate decreased approximately 24-fold when the pH was shifted from acidic pH to neutral-slightly basic pH. Sescocalcitol can be degraded by allylic conversion when acid is contained, or sescocalcitol can be decomposed.

[0156] Sescocalcitol decay was monitored by HPLC using a 5 μm LiChrospher RP-18 compressed 125 mm x 4 mm column and acetonitrile:0.01 M phosphate buffer, pH 6.0 (60:40) as the mobile phase. The flow rate was 2ml...

Embodiment 3

[0177] Improvement of Sescocalcitol Chemical Stability - Comparison of the Stability of Two Different Sescocalcitol Compositions

[0178] Stability of the composition of Example 2 containing Sescocalcitol dissolved in an aqueous vehicle containing Solutol® HS15 as solubilizer (Table 4) without any amount of organic solvent, compared with that containing ethanol-propylene glycol co-solvent (Table 5) Compared to the stability of Sescocalcitol compositions having a Sescocalcitol content of 10 or 30 μg. Compositions containing co-solvents were adjusted to specific pH values ​​(range 6.8-9.2) in order to study the effect of pH on the stability of the compositions. The composition of an example co-solvent composition with a pH of about 9 is given below:

[0179] Sescocalcitol: 10 or 30 μg

[0180] Disodium hydrogen phosphate dihydrate: 1.8mg

[0181] Sodium chloride: 3.88mg

[0182] Benzyl alcohol: 15.675mg

[0183] 99.9% ethanol: 79.2mg

[0184] Propylene glycol: 414mg

[01...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

PropertyMeasurementUnit
water solubilityaaaaaaaaaa
Login to View More

Abstract

The present invention relates to an aqueous pharmaceutical composition for parenteral administration, which composition includes i) as an active substance, vitamin D or vitamin D analogues with a water solubility of ≤0.1% at room temperature and easy degradation in an aqueous acidic environment, ii) A non-ionic solubilizer capable of dissolving the active substance, which is a low histamine releasing agent and contains polyethylene glycol esters of fatty acids optionally mixed with polyethylene glycol, as tested on the final mixture as described herein without negative effects on the stability of the active substance, and iii) an aqueous carrier. Furthermore, the present invention relates to the use of polyethylene glycol esters as nonionic solubilizers.

Description

field of invention [0001] The present invention relates to aqueous pharmaceutical compositions for parenteral administration comprising therapeutic and / or prophylactic active substances of low water solubility. Furthermore, this active substance is prone to degradation in aqueous acidic environments. Background of the invention [0002] An important route of administration for many drugs is the parenteral route. First, many drugs are not absorbed sufficiently through the gastrointestinal mucosa to achieve the systemic concentrations desired for therapeutic and / or prophylactic action. Second, in many cases a faster onset of therapeutic action is required, so parenteral administration of the drug is clearly the first choice, especially intravenous administration. [0003] Compositions for parenteral administration may be in the form of aqueous or oily solutions, dispersions, emulsions, suspensions and the like. Especially when the composition is administered intravenously, ...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/08A61K9/00A61K31/593A61K47/04A61K47/12A61K47/14A61K47/34A61P3/14A61P5/00A61P19/08A61P35/00A61P43/00
CPCA61K9/0019A61K47/14A61P19/08A61P3/14A61P35/00A61P43/00A61P5/00A61K9/08
Inventor E·J·蒂德里克森A·L·格拉奇
Owner LEO PHARMA PROD LTD AS LOVENS CHEM FAB PRODUKTIONS AS
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com