Calculated log D at pH7. Figure 1 UV-metric method for measuring pKa values. UV-metric methods provide pKa results for samples with chromophores whose UV absorbance changes as a function of pH.
It further relates to a method for preparing the formulation. Both applications are incorporated herein by reference. Field of the Invention The object of the present invention is a new formulation and a new method for producing injectable aqueous solutions containing paracetamol, and a procedure for preparation of these methods of packaging, and their utilization.
Description of the Related Art Paracetamol INN of acetaminophen or N- 4-hydroxy-phenyl acetamide is an analgesic and an antipyretic widely used in hospitals.
It is desirable to have available stable liquid pharmaceutical formulations of this active principle for administration by injection, in particular for intravenous infusion. It is known that paracetamol in aqueous solution is liable to undergo hydrolysis to form p-aminophenol, which is itself liable to degrade into quinoneimine cf.
The rate of degradation of paracetamol increases with increasing temperature and light. This rate is minimal at a pH in the region of 6 K. It is known practice to add a buffer and an antioxidant or free-radical scavenger to stabilize paracetamol in solution.
EP 0 discloses-paracetamol solutions based on a mixture of water and of alcoholic solvents comprising a buffer of pH 5. EP 0 describes a deoxygenation process by which the aqueous solvent is deoxygenated by bubbling into an inert gas, such as nitrogen.
Some of the prior-art stabilized injectable solutions of paracetamol have the drawback of requiring the total absence of oxygen during the production process. However, oxygen shows a very great facility to dissolve in water, making it necessary to ensure that the solution, once deoxygenated, does not subsequently come into contact with atmospheric air at every stage in the production process.
Even with all these precautions, total absence of oxygen can never be ensured during all the preparatory steps.
In presence of even traces of oxygen, degradation products can be generated which increase in quantity during storage of the product, and ultimately leads to a reduced shelf-life.
The main object of the present invention is to provide a formulation and a method for aqueous formulations of paracetamol, which can notably be utilized in injectable preparations being stable over a long period, which solves the problems in view of the problems of the art.
Another embodiment of the invention is a formulation as described above, wherein the inert gas is nitrogen. Another embodiment of the invention is a liquid formulation as described above, wherein the aqueous solvent has a pH between 5.
Another embodiment of the invention is a liquid formulation as described above, wherein the aqueous solvent comprises water, an isotonic agent and a buffer agent. Another embodiment of the invention is a liquid formulation as described above, wherein the isotonic agent is a polyol, a sugar, a linear or cyclic glucitol having from 2 to 10 carbon atoms selected from mannitol, sorbitol, inositol, glucose and glycerol, and preferably mannitol.
Another embodiment of the invention is a liquid formulation as described above, wherein the mass ratio of mannitol: Another embodiment of the invention is a liquid formulation as described above, wherein the sodium hydroxide is added in step iii to a final pH of between 5.
Another embodiment of the invention is a liquid formulation as described above, wherein the paracetamol is present in an amount of between 0. Another embodiment of the invention is a liquid formulation as described above, wherein the solution in step iv is subsequently filtered in a filtration unit prior to packaging in one or more vials.
Another embodiment of the invention is a method for the production of a formulation as described above, comprising the steps of: Another embodiment of the invention is a method as described, wherein the inert gas is nitrogen.Determine the y-intercept, abbreviated b, by noting the the y-value where the line crosses the y-axis.
For example, for two random points on the line at coordinates (, ) and (, ), the slope is . The amide is an important functional group present in a number of types of drugs molecules (local anesthetics, antiarrhythmics, etc). It is also the key linking moiety in proteins and peptide drug products: II.
Amide Solubility Amides contain carbonyl (C=O) and . Paracetamol PARACETAMOL (acetaminophen, N-acetyl-p-amino-phenol, 4-hydroxyacetanilide) is amoderately water-and lipid-soluble weak organic acid. It has a pKa value of and is therefore largely unionized over thephysiological rangeofpH.
Absorption Paracetamol is invariably taken orally. Absorption fromthegastrointestinal tract is bypassive.
Paracetamol N-(4-Hydroxyphenyl)ethanamide Phenacetin N-(4-Ethoxyphenyl)ethanamide Salicylic acid 2-Hydroxybenzoic acid Sodium salicylate Sodiumhydroxybenzoate Health and safety Aspirin was sent for clinical trials, Bayer manufactured the medicine and patented the process.
Feb 14, · The pKa of paracetamol is , what does this say about its absorption in the small intestine? I understand that the small intestine has a pH of around 7 and that if the pH of the environment of the drug is 2 units below the pKa value there will be almost total ionisation of the leslutinsduphoenix.com: Resolved.
This Application Note demonstrates the determination of caffeine in coffee products according to DIN , which is part of a series of quality control measurements of coffee products. The performance of the system is shown for linearity, retention time, and area precision as well as accuracy.