Codeine: Marketing Authorisation - Coursework Example

Codeine: Marketing Authorisation 1.0 Background Summary of Codeine According to WHO, Codeine is the most popular and commonly-utilised opiate across the globe. It is basically administered orally and it is considered to be the safest form of all opioid drugs (EMC, 2017). It is important to understand that Codeine is the least addictive and safest form of opiate analgesics that is ever prescribed to a patient to-date. Drug manufacturers have always opted to focus on utilising tar from opiate poppies for purposes of synthesizing morphine. In fact, it is ascertained that due to hostility of the countries for which opiate s grown, most manufacturers of the drug have resorted to conducting barter trade with heroine dealers for the purchase of the raw product. However, recently there has been the discovery of a technique that is used to get codeine from coal tar thus eliminated the competition that manufacturers suffered with illicit drug cartels. Today, the drug is evenly sorted for its medicinal purpose that relates to suppressing or even ending possible chronic coughing or rather antitussive. The medicine is mostly presented as colourless syrup and it is manufactured by Pinewood Laboratories Ltd (EMC, 2017). The drugs marketing authorisation number is PL 04917/0001 while the date of its first authorisation was 30th August 1998 and a renewal date of 20th November 2003 (EMC, 2017). Given the fact that there is a little sense of safety with the utilisation of the drug and its prescription for that matter, has resulted to a number of issues that was perfectly positioned for avoidance. It is a fact that Codeine is highly metabolised within the body to become morphine, which is a dangerous drug. Many people are perceived to be ultra-rapid metabolizers since their bodies can easily and at faster rate breakdown codeine to morphine, which might be fatal especially in small children. The drug IUPAC name is presented as below; (4R, 4aR, 7S, 7aR, 12bS)-9-methoxy-3-methyl-2,4,4a,7,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline-7-ol 2.0 The Pharmacodynamics Properties Of Codeine Codeine is morphine derivate and it is antitussive in nature-meaning that it is able to suppress the level of chronic cough reflex through a distinct direct central action through medulla or pons. It is important to note that codeine is most centrally-acting weak analgesics (Karlgren, & Bergström, 2015). For this reason, it is able to exert its immediate impact through µ opioid receptors. Despite the fact that codeine possesses a rather low affinity for these form of receptors; its analgesics impact is a direct influence of conversion to morphine state (Karlgren, & Bergström, 2015). When codeine is combined with such other analgesics as paracetamol, it has shown intensive properties in suppressing effectively and efficiently possible acute nociceptive pain. The structure of codeine is represented as below; 3.0 Physicochemical Properties Of Codeine Codeine is a colourless to a white crystalline solid or white powder that effectively sublimes at a temperature of 284oF. It is mostly odourless, with a significantly bitter taste. The drugs pH is defined as being a saturated aqueous solution of 9.8. The drugs’ colour appears as a colourless white crystal or powders. Its boiling point is positioned at 250oC or 482oF at 22mm Hg (sublimes) (EMC, 2017). The drugs melting point is at 157.5oC. Naturally occurring codeine have a definite measurement of crystalline densities of 1.32. In fact, it is safe to note that the both the melting points and crystalline density of the drug depicts a greater capacity to self-associate within their immediate crystalline state. Considering that codeine is opioids, it possesses a lower octanol water partition coefficient but higher cohesive energy densities in its immediate super cooled liquid state (PubChem, N.d). In relation to its solubility property, codeine is indeed soluble in water, benzenes, and chloroform and very soluble in ethanol. However, it is insoluble in petroleum ether. The drugs vapour pressure is 5.54X10-9 mm Hg at 25 deg C as its heat of combustion is placed at 2327.6 kg cal/g mole at 20 deg C, 760 mm Hg (solid). 4.0 Analytical Methods Available For The Assurance Of Codeine The determination of codeine (CO) is easily described by the utilisation of a single-walled carbon nanotube that is modified carbon-ceramic electrode otherwise known as the SWCNT/CCE (Milone, 2012). The preparation is made through a rather simple and robust method. The end outcomes of the analysis indicate that SWCNT/CCE would always portray exceptional electrochemical catalytic aspects that results to the oxidation of the underlying compounds in relation to CEE while still providing two anodic peaks that are positioned at 1.05 and 1.38 V visa vie a saturation of calomel electrode for purposes of oxidising CO and CF (Milone, 2012). It is important to note that the differential pulse voltammetry was adopted for the immediate establishment of both CO and CF at a distinct micromolar concentration degree. Notwithstanding, within an optimal set of conditions, it is ascertained that calibration graphs of both CO and CF will portray a linear graph within a saturated concentration of between 0.2-230 and 0.4-300uM with definite detection limits of 0.11 and 0.25 uM for both of these compounds (Milone, 2012). Another analytical method adopted for the immediate determination of codeine involves a porous silicon nanostructure that is certainly a preparation and adopted as a newer electrode material for the determination process of codeine and acetaminophen (Milone, 2012). In this method, Paladium nanoparticles are assembled within the silicon micro-particles through a mere redox reaction that exists between the Pd precursor and Psi in aqueous solution of HFL acid. These nanostructures are attributed to a different aspect of both spectroscopic and electrochemical methodologies that include scanning electron microscopy, and dispersive X-ray spectroscopy. These methods were able to achieve a linear degree of 1.0-700.0 umol L (-1) for both ACT and codeine with a detection limit of 0.4 (Milone, 2012). It is crucial to note that an apparent determination of both acetaminophen and codeine were each explored with the use of differential pulse voltammetry and the analytical method later used for the determination of both ACT and codeine in samples of blood, serum and urine. 5. How Degradation, Stability and Specificity of Codeine Test Are Done To effectively determine stability, it is noted that codeine will show stability under recommended storage condition; it results to an effloresces in a rather slow manner when exposed to dry air and it is affected by light; and, also it will be important to store CO in a temperature ranging between 15 and 30 deg while making sure to keep it off light and possible freezing (Barnes et al, 2003). To ascertain its degradation point, codeine s subjected to heat will definitely emit toxic fumes that result indicates to be nitrogen oxides. To establish its specificity, it is noted that codeine maximum absorption rate in alcohol is 212NM, with a ultra-violet rays of 5-603. It further portrays a mass of 14309 with intense mass spectral peaks of 124m/z. in testing for specificity of codeine, both immunoassay and chromatographic techniques are used (West et al, 2009). Such techniques might involve liquid chromatography that has a massive spectrometry detection limit. 6. The Pharmaceutical Formulation of Codeine The pharmaceutical formulation of codeine involves a distinct invention that results to tablets or similar product that is mainly composed of a fundamental composition of codeine as an active ingredient as well as an excipient that includes a diluent; disintegrating and fluidising agent; as well as a lubricant that is normally sodium stearyl fumarate (PubChem, N.d). The aforementioned core is certainly coated with a component that involves an integration that is entirely based on a single or in other cases a set of polymers of diversified and modified cellulose ethers as well as polymers that are directly sourced from acrylic and methacrylic acids; a plasticiser, opacifier that is mostly presented as a colouring component and any other mixture as pertains to the drug. It is crucial to note that these attributes distinguish the tablets as being an invention that is more efficacious and indeed safe. The presence of the lubricant sodium stearyl fumarate within these formulations is an indication of an almost perfect pharmaceutical form in the organism and provides a great deal of stability in the course of storage (PubChem, N.d). Of particular interest to note, the overall generation technique of codeine formulation is certainly made simpler by advanced technological models, which have acted to reduce the number of phases in the underlying production process. The efficacious and safety of the formulation is made possible as a result of a more integral potency in comparison to other formulation that are entirely related to ibuprofen and codeine. To effectively ascertain that the tablet type is of sound formulation, it is expected to comply with the following parameters; proper hardness of the tablet; stabilisation in the course of storage so that the formulation does become yellow or undergoes disintegration altogether; it achieves suitability in relation to humidity for compressing; the dissolution rate for each of the components should be based on pharmacopoeia as well as disintegration time of the tablet is also in accordance with the pharmacopoeia postulation in place (PubChem, N.d). 7. The Excipients Used In the Formulation of Codeine Sodium Benzoate (E211); is a toxic chemical compound that is mostly used as a preservative in soft drinks. It is antibacterial and antifungal in nature and effective in slightly acidic environments. Citric Acid Monohydrate: is a fundamental intermediate in the entire process of human metabolism process. Basically, the chemical compound exists as an acid that is mostly found in citrus fruits. Notably, the salts of citric acid are utilised as anti-coagulants as a result of their immediate calcium chelating capacity. Saccharin Sodium (E954); is mostly perceived as a rather sweetener that is applied most as a food additive and is generated from sodium salts. Sunset Yellow (E110); is basically a chemical compound that is used for purposes of colouring fruit and vegetable juices as well as in drugs. It is mostly petroleum-derived orange azo dye that portrays a dependent maximum absorption of more than 480 nm at pH 1. Sorbitol Solution 70% (E420); is a chemical compound that is sometimes referred to as glucitol, certainly, it is a sugar-related alcohol with a distinct sweet taste that a human body is only able to metabolise in a rather slower rate. It is generated through a possible reduction of glucose so that the aldehyde group is immediately altered to hydroxyl. It is important to note that a larger production of the compound is from corn syrup however; it can also be harvested in peaches and apples. Purified Water (to volume); is water that has been purified from possible impurities that might react with specific compounds to bring about harm in human body. Orange Flavour; is an oily liquid that is presented in orange colour that generates an orange flavour and aroma in the event that it is properly diluted. The other two notable excipients are Carboxymethylcellulose 7H3SFX and Propylene Glycol. 8. Shelf Life Prediction Data Codeine that is stored under tight and a high density polyethylene bottle are able to attain a shelf life of approximately 3 or so years. Codeine that is stored on amber glass bottles will also attain an approximate shelf life of 3 years (PubChem, N.d). It is important to note that codeine should at no particular moment in time be stored in a temperature that is above 25C and should be protect from possible light rays. 9. Side Effect and the Risk of Overdose A successful partaking of the drug will mostly result to gastrointestinal effects, constipation; loss of appetite as well as possibility of respiratory depression and sputum retention. In the case of overdoes, immediate supportive therapy is suggested (PubChem, N.d). For this case, gastric lavage should be conducted and administration of saline purgative be done to eliminate possible absorption from gastro-intestinal tract. Intravenous naloxone HCL should be administered in the event that there is serious respiration. 10. Conclusion Codeine is the most popular and commonly-utilised opiate across the globe and it is basically administered orally and it is considered to be the safest form of all opioid drugs. The drugs marketing authorisation number is PL 04917/0001 while the date of its first authorisation was 30th August 1998 and a renewal date of 20th November 2003. IUPAC name is (4R, 4aR, 7S, 7aR, 12bS)-9-methoxy-3-methyl-2,4,4a,7,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline-7-ol. Codeine is morphine derivate and it is antitussive in nature-meaning that it is able to suppress the level of chronic cough reflex through a distinct direct central action through medulla or pons. Codeine is indeed soluble in water, benzenes, and chloroform and very soluble in ethanol. However, it is insoluble in petroleum ether. The drugs vapour pressure is 5.54X10-9 mm Hg at 25 deg C as its heat of combustion is placed at 2327.6 kg cal/g mole at 20 deg C, 760 mm Hg (solid). The determination of codeine (CO) is easily described by the utilisation of a single-walled carbon nanotube that is modified carbon-ceramic electrode otherwise known as the SWCNT/CCE. References Barnes, AJ et al. (2003). Sensitivity, specificity and efficiency in detecting Opiates in oral fluid with the Cozart Opiate microplate EIA and GC-MS following controlled codeine administration. Journal of Analytical Toxicology, 27, 402-406 EMC. (2017). Codeine Linctus BP. Retrieved from https://www.medicines.org.uk/emc/medicine/24373#UNDESIRABLE_EFFECTS Karlgren, M., & Bergström, C. A. (2015). How Physicochemical Properties of Drugs Affect Their Metabolism and Clearance. Milone, M. C. (2012). Laboratory Testing for Prescription Opioids, 8(4), 408–416. http://doi.org/10.1007/s13181-012-0274-7 PubChem. (N.d).Codeine: Compound Summary for CID 5284371. Retrieved from https://pubchem.ncbi.nlm.nih.gov/compound/codeine#section=Top West R, Crews B, Mikel C, Almazan P, Latyshev S, Pesce A, et al.(2009). Anomalous observations of codeine in patients on morphine. Therapeutic Drug Monitoring; 31(6):776–778 Read More