TN2011000430A1 - FORMULATION OF A STABLE PARACETAMOL LIQUID SOLUTION FOR PERFUSION AND METHOD FOR PREPARING THE SAME - Google Patents

FORMULATION OF A STABLE PARACETAMOL LIQUID SOLUTION FOR PERFUSION AND METHOD FOR PREPARING THE SAME

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Publication number
TN2011000430A1
TN2011000430A1 TN2011000430A TN2011000430A TN2011000430A1 TN 2011000430 A1 TN2011000430 A1 TN 2011000430A1 TN 2011000430 A TN2011000430 A TN 2011000430A TN 2011000430 A TN2011000430 A TN 2011000430A TN 2011000430 A1 TN2011000430 A1 TN 2011000430A1
Authority
TN
Tunisia
Prior art keywords
paracetamol
formulation
agent
water
oxygen
Prior art date
Application number
TN2011000430A
Other languages
French (fr)
Inventor
Sadok Zgarni
Original Assignee
Dorcas Lab
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Dorcas Lab filed Critical Dorcas Lab
Priority to TN2011000430A priority Critical patent/TN2011000430A1/en
Publication of TN2011000430A1 publication Critical patent/TN2011000430A1/en

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Abstract

La présente invention concerne des formulations pharmaceutiques stables renfermant du paracétamol dans un solvant aqueux. Le paracétamol ( DCI de l'acétaminophène ou N-(4-hydroxyphényl) acétamide) est un analgésique et un antipyrétique largement employé en milieu hospitalier. La vitesse de dégradation paracétamol croit avec l'augmentation de la température et à la lumière. La présente invention a pour objet de résoudre les problèmes de stabilité de la molécule d'une manière commode et satisfaisante. Le solvant aqueux peut etre de l'eau ou bien des mélanges aqueux renfermant de l'eau et un polyol comme le propylène glycol ou le polyéthylène glycol (PEG). on peut également utiliser un alcool soluble dans l'eau, comme l'éthanol. La stabilité de ces solutions aqueuses est déterminée également par d'autres paramètres , comme l'ajustement judicieux du pH, l'élimination de l'oxygène dissous dans le véhicule, l'adjonction d'un agent antioxydant ainsi que le recours à un traitement thermique pour éliminer toute trace de nucléation du paracétamol. La formulation de l'invention préconise l'élimination de l'oxygène dissous par barbotage d'un gaz inerte tel que l'azote pur et exempt d'oxygène, comme elle contient un agent tamponnant de pKa compris entre 4,5 à 6,5 , de préférence le plus proche de 5,5. Cet agenttamponnant sera avantageusement choisi parmi les tampons acétate , citrate, phosphate, phosphate-citrate,bicarbonate , tampon tartrate. Cette formulation pour injection contient un agent isotonisant, destiné à créer une pression osmotoque voisine de celle du sérum physiologique?Cet agent isitinisant est choisi parmi le chlorure de sodium , le sorbitol ou le glucose. La formulation de l'invention est préparée d'abord par mélange d'eau exempte d'oxygène , à une haute température , de co-solvant, d'agent isotonisant, d"antioxydant, d'agent tamponnant. Le paracétamol est introduit dans ce mélange et agité jusqu'à complète dissolution sous barbotage de gaz inerte en continu. La préparation, en vrac ou remplie dans des récipients, subit un chauffage à une température d"au moins 70°C pendant une durée d'au moins 15 minutes. Ce chauffage a pour but d'éliminer toute trace de nucléation qui pourrait lors du stockage de la solution déclencher une recristallisation du paracétamol. Les formules retenues et qui ont montré une stabilité vérifiée par des études de vieillisement accéléré et en temps réel selon les exigences de l'ICH a permis l'obtention d'une autorisation de mise sur le marché octroyée par le ministère de la Santé Publique de Tunisie.The present invention relates to stable pharmaceutical formulations containing paracetamol in an aqueous solvent. Paracetamol (INN acetaminophen or N- (4-hydroxyphenyl) acetamide) is an analgesic and antipyretic widely used in hospitals. The rate of degradation paracetamol increases with increasing temperature and light. The object of the present invention is to solve the stability problems of the molecule in a convenient and satisfactory manner. The aqueous solvent may be water or aqueous mixtures containing water and a polyol such as propylene glycol or polyethylene glycol (PEG). it is also possible to use a water-soluble alcohol, such as ethanol. The stability of these aqueous solutions is also determined by other parameters, such as the judicious pH adjustment, the removal of dissolved oxygen in the vehicle, the addition of an antioxidant and the use of a treatment. to remove any trace of nucleation from paracetamol. The formulation of the invention recommends the removal of dissolved oxygen by bubbling an inert gas such as pure nitrogen and oxygen-free, as it contains a buffering agent of pKa between 4.5 to 6, 5, preferably the closest to 5.5. This buffering agent will advantageously be selected from acetate, citrate, phosphate, phosphate-citrate, bicarbonate and tartrate buffer buffers. This formulation for injection contains an isotonicizing agent intended to create an osmotochic pressure close to that of physiological saline This isitizing agent is chosen from sodium chloride, sorbitol or glucose. The formulation of the invention is prepared firstly by mixing oxygen-free water, at a high temperature, co-solvent, isotonizing agent, antioxidant, buffering agent, paracetamol is introduced into This mixture is stirred until completely dissolved while bubbling inert gas continuously.The preparation, in bulk or filled in containers, is heated at a temperature of at least 70 ° C. for a period of at least 15 minutes. . This heating is intended to eliminate any trace of nucleation that could during the storage of the solution trigger a recrystallization of paracetamol. The selected formulas, which showed a stability verified by accelerated and real-time aging studies according to the ICH requirements, made it possible to obtain a marketing authorization granted by the French Ministry of Public Health. Tunisia.

TN2011000430A 2011-08-19 2011-08-19 FORMULATION OF A STABLE PARACETAMOL LIQUID SOLUTION FOR PERFUSION AND METHOD FOR PREPARING THE SAME TN2011000430A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
TN2011000430A TN2011000430A1 (en) 2011-08-19 2011-08-19 FORMULATION OF A STABLE PARACETAMOL LIQUID SOLUTION FOR PERFUSION AND METHOD FOR PREPARING THE SAME

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
TN2011000430A TN2011000430A1 (en) 2011-08-19 2011-08-19 FORMULATION OF A STABLE PARACETAMOL LIQUID SOLUTION FOR PERFUSION AND METHOD FOR PREPARING THE SAME

Publications (1)

Publication Number Publication Date
TN2011000430A1 true TN2011000430A1 (en) 2013-03-27

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
TN2011000430A TN2011000430A1 (en) 2011-08-19 2011-08-19 FORMULATION OF A STABLE PARACETAMOL LIQUID SOLUTION FOR PERFUSION AND METHOD FOR PREPARING THE SAME

Country Status (1)

Country Link
TN (1) TN2011000430A1 (en)

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