Practical: Injectable Solution of Paracetamol - Essay Example

Figure1: Simple schema of paracetamol metabolism

(OPEN SOURCE CLINICAL TOXICOLOGY CURRICULUM, 2008)

The diagram above is a simple schema of the metabolism of paracetamol. There are various variables that possibly influence the toxicity’s risk factor.  These are well appreciated by comprehending the paracetamol’s toxicokinetics.

Another reason for the dominance of paracetamol is that human beings easily tolerate it in their system since it does not alter the human acid-base equilibrium when injected into the body. Due to this, paracetamol has been used intensively and widely as a pain reliever in children, adults, and elderly people (Gray, 2009; pg. 82). Large volumes of pharmaceutical preparations are commonly administered orally. However, it has ever remained difficult to obtain such pharmaceutical preparations for injections especially solutions that are ready to use for intravenous perfusion (Watson, 2012; pg. 29). Such solutions are usually difficult to find since paracetamol is insoluble in water and its aqueous solutions are unstable in oxygen and/or light presence. In these conditions, paracetamol is usually decomposed through degradation plurality pathways. Such instability of aqueous paracetamol is contributed by the availability of degradation substances in this solution that in most cases cause the paracetamol solution to color (Hospitals, 2013; pg. 172). An illustration of the degradation process is in the diagram below:

Figure 2: Advanced Oxidation Chemistry of Paracetamol

(Vogna D,  Marotta R, Napolitano A, and d'Ischia M, 2002)

The diagram above shows the major degradation pathways that are derived from three steps of hydroxylation, that lead to the 1,4-benzoquinone and 4-acetylaminocatechol, and even to a 4-acetylaminoresorcine. The primary aromatic intermediates oxidation, viz. 1,4-hydroquinone, a 2,4-benzonitrile,  and 4-acetylaminocatecho result in products of nitrogenous and non-nitrogenous degradation.

The substances that cause the colorisation of the paracetamol solution include benzoquinoneimines among other human hepatotoxins. Based on this knowledge, this experiment is being conducted with the aim of preparing paracetamol solution for IV injection, test it for API content using HPLC and check its quality based on particles' appearance.

         Additionally, this experiment also aims at determining the main causes of paracetamol solution degradation (Gibaldi, Lee, and Desai, 2007; pg. 536). Colorisation is usually caused by interference in light rays whereby particles or substances once strike by light absorb other colors and reflect their own (Sinatra, 2009; pg. 200). Therefore, this experiment aims at applying light reflection and interference principles to determine the major particulate matter contaminant that may be present in laboratory prepared paracetamol solution for IV injection.

            Different clarity tests for detecting the presence of particulate matter in solutions are usually available in chemical and pharmaceutical laboratories (Schrör, 2009; pg. 93 and Reinhold and Earl, 2014; pg. 311). However, methods that are mainly used in testing parenteral products include electronic particulate counting and visual inspection (Bonewit-West, Hunt, and Applegate, 2013; pg. 273; Pryde and Gilbert, 1980; pg. 39; and Troy, 2005; pg. 51). The visual inspection usually uses the naked eye to inspect the presence of foreign materials or particulate matter in any laboratory or industrially prepared solution. In this regard, the light reflection principle is to be applied in this experiment as a means of visual inspection where the solution will be placed behind black and white backgrounds (Braverman, 20013; pg. 292). The white background will facilitate the visibility of the dark-colored particles since the light-reflecting particles will appear on the black background. In cases where visibility may be bared, it will be appropriate to use visual enhancing equipment such as the magnifying lens.

          It is advised that particulate matter should never be in any injectable pharmaceutical preparations especially when such particulate matter can be inspected visually. Any injectable solution is only considered to have acceptable or standard suspensions if such suspensions cannot be determined visually. Particularly the visually notable particulate matter in the injectable solutions is usually fatal and can cause other complications to the human internal organs. For instance, such particulate matter may block veins; thus, causing injuries to the internal tissues among other complications. Therefore, any procedure for the preparation of an injectable solution of paracetamol among other drugs must ensure that all laboratory quality and quantity standards are adhered to, in order to minimize or eradicate the introduction of foreign materials into the final products.