Synthesis of Research Problem, Method, and Design-Hypothetical Designs Paper

Synthesis of Problem, Method, and Design-Hypothetical Designs - Research Paper Example These challenges, which include dishonesty and plausible misjudgments, threaten the quality of results obtained through this process. Certain measures have, however, been put in place, to ensure high quality, and error free results. There is little or no attention given to the efficiency and throughput of the crowdsourcing process or the integrity of the results obtained. It is argued that the numbers of task workers and tasks are always small, thereby, resulting in crowdsourcing techniques that are not conscious of the number of tasks, potential worker behavior and efficiency of the process. This research aims at proposing a crowdsourcing, result-improvement technique that is independent of task complexity and sizes and ensures result quality, integrity, as well as efficiency and throughput of the process. The hypothesis being studied in this case is that crowdsourcing result-improvement techniques that are task size and complexity independent ensures result integrity, quality, effi ciency as well as throughput. Hypothetical Designs Quantitative design This design will utilize experimental research method - methods that aim at maximizing replicability, generalizability, and objectivity of results; mostly concerned with prediction (Creswell, 2009). The focus will be to test several existing crowdsourcing techniques including r-Redundancy, v-Voting, and Vote Boosting techniques on a large number of tasks that will be handled by a large number of users. These techniques will be considered as experiment participants. The independent variable in this case would be the crowdsourcing techniques, including r-Redundancy, v-Voting, Vote Boosting techniques and the technique that this research will propose. The independent variables will be studied in two level; low task, less complex task level, and high number of tasks, and complex tasks level. Consequently, the dependent variables will be integrity, quality, efficiency as well as throughput. The experiment will be set in such a way that, the tasks set for testing, will have two definitive parameters including the accuracy of the tasks initial states and the number of options available per decision. 8 sets of 100,000 tasks with 3, 4, or 5 options and 75%, 85%, and 95% as the accuracy for the initial set tasks. There are about 4 to 10 decisions distributed normally. The user network or population tested also has two parameters including mean probability for committing errors and for dishonesty. Values of 3%, 6% and 20% are used for both dishonesty and making of errors. These probabilities were distributed exponentially over [0, 1] around their mean values. Simulations for about 40 input-aggregation functions with each one receiving one input are run repeatedly. For this experiment, the proposed quantitative hypothetical design is deemed to be extremely expensive even in the event that only few points in a parameter space are covered. Qualitative Design In this case, this research method will aim at understanding and discovering the perspectives, thoughts and experiences of previous researchers and participants in the same field in order to understand reality, purpose and meaning (Trochim & Donnelly, 2008). The focus will be to review and evaluate literature on previous and current research

Although we need regulation on internet for many reasons, the U.S Essay

Although we need regulation on internet for many reasons, the U.S government should not regulate internet because it could endanger e-business - Essay Example Internet was invented to facilitate the information collection system and communication of the USA military force. However, with the increased use of computer over time and sharp fall in computer prices, Internet made its entry into the households in the 80s and more effectively during 90s. Soon Internet became popular in almost all the developed countries and made its way into the developing countries as well. The 90s witnessed a sharp decrease in computer prices owing to the continuous research and development in the field of Information Technology and efficient, smaller and cheaper computers had been invented during this period. At the same time Internet became more and more available due to spread of optical fiber at a mass level and its price fell due to the emergence of competing organizations in the field of Internet service providers. The situation was perfect for the Internet to spread at the onset of the new millennium and it made an optimum use of that situation to spread even at a much faster rate than before and made a much deeper drive than it had ever made since its inception. The U.S government should not regulate Internet because it could endanger e-business. Firstly, Internet is readily available to anyone and even that at a cheap rate. The ready availability is due to the spread of optical fiber beneath the seawater, which has made possible the continental connectivity and the cheaper price is due to the competitive nature of the Internet service providers’ market. If one service provider asks a little higher price he would surely lose customers, as the customer will get the same service at a cheaper rate. Secondly, Internet is brilliant for getting any information, from weather condition to railway availability. All these can be known by a click of the mouse and comparing to its information providing capability, the

A questionnaire for a career choice Term Paper Example | Topics and Well Written Essays - 1000 words

A questionnaire for a career choice - Term Paper Example A questionnaire for a career choice To begin with, she needed a career path and a sound decision towards the same. She seems to possess confusion as regards her interests. She seems to love poker, cooking, gardening and working out. On the other hand, she has been both a player and a coach of tennis and basketball. It is vital to note that she had an earlier fantasy of being a sports’ writer. There are core problems that she seeks to address through counseling and possible solutions. To begin with, the client has a problem of career choice. She seems not to be satisfied of her current job of bier a consultant at a firm that write programs for professionals. In addition to the same, she has psychological problems. Lastly, she possesses a problem that of balancing her career ambitions with that of her children and her husband. It is vital to note that the client possesses psychological and mental problems. The treatment of the same is essential because it affects the career progress of Alaina. In this sense, the c lient is medically proven to be suffering from a mild form of depression. The medical name of this depression is dysthymia. The suicide and eventual death of a cousin might have triggered this depression. As regards this depression, she has been attending counseling sessions for eight months. It is vital to note that she has had counseling sessions over anger management problems. This also relates to previous anger problems at her school sessions. This is the factor that contributed to her career diversion from teaching to consultancy. This was vital for stabilizing her marriage and finding a sound career line. In this sense, she takes medicine in form of depression tablets. However, she still possesses a problem of suppression to feelings of good things in her life. This means she has no feelings of impression for good things in her life. In addition, she possesses anxiety and sleeping problems. Alaina possesses notable strengths and shortcomings. In her career ambitions and passio ns, Alaina seems to have a robust orientation towards writing. This is notable from her course in college. She had a college course of B.A in English and a minor in journalism. It is crucial to note that this was her subject in her schooling days. Her present job entails offering consultancy services for a firm that write career programs. It is notable that her career ambitions entail being an editorial assistant for a publishing firm or technical writing. In addition, she had an earlier fantasy of being a sports’ writer. Besides, Alaina seems to be aware of her interests. In this sense, she has strong decisions of not preferring educational careers. However, Alaina has anger management problems. This attributes to her uncontrolled anger during her teaching days. In this sense, Alaina needs to work on social relation skills. This regards appropriate emotional response to situations. In our working relationship with the client, I will ensure notable ideas for a solid working r elationship. To begin with, my strategy would involve eliminating the professional outlook to the client. This would be appropriate for establishing an intimate relationship with

Although we need regulation on internet for many reasons, the U.S Essay

Although we need regulation on internet for many reasons, the U.S government should not regulate internet because it could endanger e-business - Essay Example Internet was invented to facilitate the information collection system and communication of the USA military force. However, with the increased use of computer over time and sharp fall in computer prices, Internet made its entry into the households in the 80s and more effectively during 90s. Soon Internet became popular in almost all the developed countries and made its way into the developing countries as well. The 90s witnessed a sharp decrease in computer prices owing to the continuous research and development in the field of Information Technology and efficient, smaller and cheaper computers had been invented during this period. At the same time Internet became more and more available due to spread of optical fiber at a mass level and its price fell due to the emergence of competing organizations in the field of Internet service providers. The situation was perfect for the Internet to spread at the onset of the new millennium and it made an optimum use of that situation to spread even at a much faster rate than before and made a much deeper drive than it had ever made since its inception. The U.S government should not regulate Internet because it could endanger e-business. Firstly, Internet is readily available to anyone and even that at a cheap rate. The ready availability is due to the spread of optical fiber beneath the seawater, which has made possible the continental connectivity and the cheaper price is due to the competitive nature of the Internet service providers’ market. If one service provider asks a little higher price he would surely lose customers, as the customer will get the same service at a cheaper rate. Secondly, Internet is brilliant for getting any information, from weather condition to railway availability. All these can be known by a click of the mouse and comparing to its information providing capability, the

Special Education Research Critique Essay Example for Free

Special Education Research Critique Essay REFERENCE Rickson, D. J., Watkins, W. G. (2003). Music therapy to promote prosocial behaviors in aggressive adolescent boys A pilot study. _Journal of Music Therapy, 40_(4), 283-301. PURPOSE The hypothesis of this research study was to determine if music therapy would help promote prosocial behaviors in aggressive boys. These subjects have different social, emotional, and learning disorders. METHOD The subjects were selected from a group of 88 young boys who have intellectual, social, and emotional deficits. These boys were enrolled in a special education facility in New Zealand. The students who started before May 2000 and after March 2001, which was 49 students, were not included because of the likelihood of them leaving before the study was completed. This left a remaining 39 students. These students were given the Child Behavior Checklist (CBCL) test. A total of 21 students were excluded due to lack of aggressiveness and already gone through musical therapy. Researchers were left with 18 boys whose ages ranged from about 11 years and six months to 15 years and three months. These subjects had an extreme measure on the CBCL test. 12 of the boys were already diagnosed with Attention Deficit Disorder (ADD) or Attention Deficit Hyperactivity Disorder (ADHD). Of the 12, five had a dual diagnosis which included Oppositional Defiant Disorder (ODD) or Conduct Disorder (CD). Four had a general developmental delay and two had a head injury along with depression. About half of the boys were taking psychotropic medication. They were randomly assigned into two music groups of six and one control group of six. One subject was suspended right after the therapy began. Another quit after a few minutes into a session. Also, one more was suspended from school after one session due to extreme  disruptive and aggressive behavior. A total 15 students completed the treatment. The treatment was the participants were placed into different music groups. In the music groups, the students would do different musical activities and express themselves through music. RESULTS There was an increase in disruptive and aggressive behavior in Group 1. This is a negative result due to the treatment. Group 2 had no changes in behavior. Group 3 also had little to no change in their behavior at school. AUTHORS CONCLUSION No significant statistical differences were found after the treatment was completed. Because there was no difference, there can be no definitive conclusion to be made by the author. Some social workers did record small improvements that were interesting and could lead to further study. They noted that the subjects were not as aggressive as they were before the research study. The author would also like to try to do another study but have it be based on a specific diagnosis of the subject. PRACTICAL APPLICATIONS The usefulness of this treatment is very minimal. The results after the treatment was conducted were negative or neutral overall. If I were to try and implement it into a classroom environment, I am not sure if it will be helpful in any way. CRITIQUE I feel like this study not fully prepared or researched. The researchers did states their hypothesis, addressed the results, and the sample size. But the treatment itself was not successful. The sample size for this kind of treatment should have been bigger than just 15 students. The researchers could have gone and tested other schools or even elementary and high school.  A sample size of 15 subjects cannot represent 100 subjects. In conclusion, this musical treatment study was not well planned out.

Dissolution Profile of Paracetamol Generics

Dissolution Profile of Paracetamol Generics 1 Introduction The pharmaceutical industry had an estimated turnover of $773 billion in 2008,1 however not all of this revenue was taken as profit; a significant cost goes into research and industry guideline compliance. With regards to new generic medications, proving bioequivalence is crucial to success, however necessary in vivo testing can be costly.2 Drugs which meet certain Biopharmaceutics Classification System (BCS) criteria may be exempt from these expensive tests and can be permitted a biowaiver.3 This allows in vitro dissolution testing in place of in vivo plasma analysis. Paracetamol is one such drug that has qualities which place it at the borderline of biowaiver suitability.3 It is the worlds most commonly used analgesic4 and the question arises as to whether all preparations are as effective as each other? More specifically we ask, is there is any significant difference between the dissolution profile of paracetamol generics? This literature review is in preparation of experimental t ests designed to ascertain if there is any difference in dissolution profile of eight bioequivalent preparations listed on the Australian Pharmaceutical Benefits Scheme (PBS), and whether this difference may correlate to a clinical significance in such a common place drug. 2 Search Strategy All data was sourced through internet databases, i.e. Medline, Pubmed, and the Cochrane Library. The search engines Google Scholar and UWA library were also utilized. Keywords included. KEY WORDS Paracetamol, acetaminophen, bioequivalent (therapeutic equivalency), Delayed-action Preparations, Pharmaceutical Preparations, Tablets, Drug Compounding, Chemistry, Pharmaceutical, Observer Variation, Dissolution, Metabolism, in vitro, in vivo, IVIVC, Drug Content, Bioavailability and Correlation. Boolean searching was utilised to broaden or narrow search results and once appropriate articles were sourced, citing and cited articles were also evaluated. 3 Paracetamol 3.1 History Paracetamol (acetaminophen) is one of the worlds most popular drugs for the treatment of pain and fever.4 It was first synthesized in 1878 by Morse, and was used clinically for the first time in 1887 by von Merring.4, 5 Paracetamol fell into obscurity shortly thereafter in favour of other chemically related drugs such as phenacetin.5 However, phenacetin was later found to be nephrotoxic, and the search for a substitute arose.5 In 1950, a study from Brodie and Axelrod rediscovered paracetamols suitable analgesic properties.4 Although, this drug did not experience widespread acceptance until the 1970s due to unfounded concerns about safety; but from then on, it became the most commonly used medication for pain.4 In many countries, such as the United Kingdom, paracetamol sales have exceeded those of aspirin since 1980.4 3.2 Physicochemical properties Paracetamol or N-(4-hydroxyphenyl) acetamide, is a white crystalline powder with a melting point of 168-172C (Martindale). It is sparingly soluble in water, ie. one part of paracetamol is soluble in 70 parts of water at room temperature.3 It is also freely soluble in alcohol. (Martindale) Paracetamol shows maximal UV absorption at a wavelength of 249nm and is reported to have a pKa of 9.5 at 25C.3 3.3 Pharmacology Pharmacokinetics 3.3.1 Pharmacodynamics Mechanism of Action The exact mechanism of action of paracetamol has remained largely unknown for some time.6-9 For years it has been thought to inhibit the enzyme cyclooxygenase (COX) in a similar manner to non-steroidal anti-inflammatory drugs, however definitive proof of analgesia and antipyresis being dependent on COX inhibition is still lacking.4 Recently, two independent groups have produced experimental data that has demonstrated that analgesia involves the potentiation of the cannabinoid vanilloid tone in the brain and in the dorsal root ganglia.4 Blockade of cannabinoid (CB1) receptors in rats has eliminated any analgesic properties of paracetamol and suggests that paracetamol is in fact a cannabinomimetic.4 3.3.2 Pharmacokinetics 3.3.2.1 Absorption Bioavailability: Paracetamol has been reported to have a bioavailability of 62%-89% in those of a fasted state,3, 8 this divergence from absolute bioavailability is attributed to first pass hepatic metabolism. Peak plasma concentrations are reached between 0.17-2.0 hours post-dosing.10 As expected, food has been shown to reduce absorption by increasing tmax and decreasing Cmax values. Food has not been shown to affect the amount of acetaminophen reaching the blood.3 3.3.2.2 Distribution: Paracetamol has a reported volume of distribution of 0.69-1.36L/Kg.11 Around 20%-25% of the drug is bound to plasma proteins at therapeutic dosages; however this value has been shown to increase to 20%-50% in over dosage. Paracetamol has also been shown to cross the placenta, and has a 1.24 milk/plasma ratio in breast milk.3 Paracetamol is an ADEC category A drug, i.e. it is safe to use in pregnancy, as well as breastfeeding.9 3.3.2.3 Metabolism Excretion: Around 85%-90% of paracetamol is metabolized within the liver via the process of glucuronidation and sulfation.3 These inactive metabolites are then eliminated by the kidney in the urine. Approximately 5% of paracetamol is passed out unchanged in the urine, the remaining drug is conjugated with cysteine and mercapturic acid.3, 8 The half-life of paracetamol has been reported as 1.9 4.3 hours3, 8, 10 but longer in those with renal impairment. 3.4 Indication Paracetamol is indicated in the symptomatic treatment of mild-to-moderate pain as well as fever3, 9 and has also been described to have mild anti-inflammatory properties.3 3.5 Dose Dosage Forms For adults, the optimal single dose of paracetamol is 1g,3, 9 with a maximum dose of 4g daily.9 Hepatocellular necrosis can occur from doses of 10-15g, and death may result in doses in excess of 20-25g.3 Paracetamol is available in many dosage forms, as a single active pharmaceutical ingredient (API), or in combination with other analgesics such as codeine (Panadeine), dextropropoxyphene (Di-Gesic), metoclopramide (Metomax), as well as in combination with decongestants such as pseudoephedrine in cold-and-flu preparations.9 This drug is available as immediate release (IR) tablets, sustained release (SR) tablets, chewable, elixirs, IV injections and suppositories.9 4 Biopharmaceutics Classification System The Biopharmaceutics Classification System (BCS) is a method of grouping active pharmaceutical ingredients (API) based on their solubility and intestinal permeability.12-16 The system allows for easy identification of those drugs whose in vivo absorption can be easily anticipated based on their in vitro dissolution.12, 15, 16 This implies that two different products containing the same drug will have the same rate and extent of absorption if, over time, they both have the same concentration profile at the intestinal membrane.12 Since it is the dissolution profile of a drug which determines its concentration profile in the intestinal lumen, comparability of this parameter in vitro should produce comparable absorption results in vivo.12 In reality however, only those drugs with high permeability which are formulated into IR preparations can be easily and reliably applied to this logic.12, 15, 16 4.1 BCS Drug Classes There are four classes within the BCS to which a drug can be assigned (as outlined in figure 1). Class I is comprised of those drugs with high permeability and solubility, these drugs are expected to be well absorbed and, providing dissolution is slower than gastric emptying, show a good correlation between in vitro dissolution rate and the rate and extent of in vivo absorption (IVIVC).12, 15, 16 Class II drugs also have high permeability but their solubility is low which ensures in vivo dissolution is the rate limiting step in drug absorption and thus IVIVC is expected.12 Class III drugs have a low permeability with high solubility, traditionally these drugs were believed to have little or no IVIVC,12 however recent studies have shown that if a class III drug is very rapidly dissolving then a correlation may exist.18, 19 Finally Class IV drugs have both low permeability and solubility these drugs are not expected to show any IVIVC.12 For each of the four BCS classes a drug substance is considered highly soluble when the highest [IR] dose strength is soluble in 250mL or less of aqueous media over the pH range of 1-7.5.16 The permeability of a drug is considered high if greater than 90% of a dose is absorbed across the intestinal membrane.16, 20 Using these definitions, paracetamol is classified as a BCS class III drug but it is also described as borderline class I because it is only just on the cusp of low permeability.3 4.2 Utility of the BCS The genius of the BCS is that it allows easy identification of drug candidates for which relatively cheap and fast in vitro dissolution testing can replace the more expensive, time consuming and invasive in vivo absorption testing.2 The system does away with complex bioavailability modeling that must account for fasted and fed states as well as cyclical changes in motility and gastric emptying.12, 14 The impact of the BCS on the pharmaceutical industry was so great that in 2006, creator Dr. Gordon Amidon was awarded the International Pharmaceutical Federation (FIP) Distinguished Scientist Award.21 5 Correlation between in vitro dissolution and bioavailability Following the introduction of the BCS a great deal of research was conducted exploring the power of IVIVC. It became a main focus not just of the pharmaceutical industry but also of academia and regulatory authorities.2 IVIVC became popular because it can be used as a substitute for resource intensive bioavailability testing; the concept has essentially improved the speed and cost of drug development as well as quality control in pharmaceutical manufacturing.2 5.1 Bioavailability and Bioequivalence Bioavailability is an important concept because it determines the efficacy, safety and reproducibility of the therapeutic effect of drugs and the many formulations in which they come.22 For the purpose of drugs that produce a systemic therapeutic effect, the Australian Therapeutic Goods Administration (TGA)22 defines bioavailability as the extent and the rate at which a substance or its active moiety is delivered from a pharmaceutical form and becomes available in the general circulation. Bioavailability is therefore inherently linked to drug absorption and may also be predicted using IVIVC as defined by the BCS. If two pharmaceutically equivalent (same active ingredient and content in the same formulation) products have the same bioavailability they are considered bioequivalent and will essentially have the same efficacy and safety. Bioequivalence is important because it is the basis for which innovator medicines can be substituted with generics. 5.2 Strength of in vitro in vivo correlations The BCS is a predictive tool for determining which drugs will have an IVIVC. Table 1 demonstrates that under the BCS only class II along with some class I drugs are expected to have IVIVCs.12 Research subsequent to Dr. Amidons first BCS publication has generally upheld his initial findings however exceptions to the rule have been found. 5.2.1 Drugs with IVIVC The BCS suggests that if the bioavailability of a drug is dissolution rate limited then a good IVIVC should be possible. This notion has been demonstrated for flutamide a very poorly soluble high dose compound which is not expected to have IVIVC but has dissolution rate limited absorption.23 A paper published by Posti, Katila Kostiainen23 concluded that there is a strong IVIVC for flutamide and this was identified on four separate occasions where bioavailability was studied. All four studies were of single dose, cross over design and each subsequent study increased the number of subjects tested (study I: n = 6, Study IV: n = 24). The strength of the papers methodology provides good support for its conclusions however this was undermined by a lack of documented statistical analysis. Much more compelling evidence comes from a study by Sakuma et. al.24 which was able to show an IVIVC for two BCS class I drugs after they received an enteric coating, thus eliminating the possibility that gastric emptying was the rate limiting step. The results were statistically significant, however the tablets were tested in rat models rather than human subjects and the dissolution test may not have adequately reflected the in vivo environment that enteric coated tablets are subject to.24 Further studies in human subjects demonstrating the difference in IVIVC between enteric and non-enteric coated tablets could not be identified in the literature. There are hundreds of other drugs which have an IVIVC and these are neither limited to BCS class II drugs or drugs with dissolution rate limited absorption. Theophylline is a BCS class IV drug and yet in a complete cross over study of four different theophylline tablets the in vitro dissolution was able to significantly predict several in vivo pharmacokinetic parameters (AUC Cmax) which dictate bioavailability.25 The study was small (n = 6) and not all pharmacokinetic parameters could be correlated. Other common drug examples with IVIVC include digoxin,26 rifampicin,27 diclofenac28 and lamotrigine29 and these are by no means exhaustive. 5.2.2 Drugs without IVIVC Not all drugs have an IVIVC and this can also include some BCS class II drugs. A research paper by Frick, Moller Wirbitzki 199830 demonstrated that the in vitro dissolution of glimepiride (BCS class II) is not comparable to dissolution in vivo. The study employed a single dose cross-over design with 12 subjects, Latin-Square statistical analysis was employed and the results were assumed to be significant however not all the data was accompanied by supporting confidence values. No correlation was possible because the solubility of glimepiride is low and strongly pH dependent.30 Unlike glimepiride, ciprofloxacin a quinolone antibiotic, is classified as a BCS class III drug and as a consequence would not be predicted to have an IVIVC. Correspondingly, when tested for this possibility none could be found between dissolution and any of the parameters for bioavailability (Tmax, Cmax, AUC Ka).31 5.2.3 Strength of BCS in predicting IVIVC There is a wide variance between IVIVCs that are anticipated according to the BCS and those that are actually demonstrated after experimental testing. Examples have been provided where both expected and unexpected correlations occur and this suggests that the BCS system while helpful should only be taken as a guide. Laboratory testing is still the only reliable method for determining if a correlation is occurs. Paracetamol is a BCS class III medication and as such is not expected to demonstrate strong IVIVC. Given the fact that paracetamol has a wide therapeutic index and the BCS can only be used as a guide, a safe and useable IVIVC may still exist. 5.2.4 IVIVC of paracetamol The prodigious use, vast quantities manufactured and the presence of many generic products in the marketplace makes paracetamol a prime candidate for IVIVC testing. In 1996 Retaco et. al.32 conducted a small crossover study using five subjects to assess whether an IVIVC for paracetamol may exist. The study stated that the absorption data from saliva partially correlated with those found in vitro,32 this however is not a valid conclusion. One of the subjects studied produced in vivo data that opposed a correlation and this anomaly was further confounded by the fact that statistical analysis was not performed on the IVIVC but rather covered the in vitro and in vivo data separately. This pilot study was later contradicted by Babalola et. al.33 who found limited IVIVCs and suggested that paracetamol absorption may not be limited by its dissolution rate. Similarly, a thorough, well designed, complete crossover (44) study that balanced for first order residual effects, suggested that it wa s dangerous to use dissolution as the sole test for paracetamol bioequivalence.34 Interestingly, all of these studies demonstrated bioequivalence between the various products of paracetamol even if they showed no IVIVC. 6 Biowaiver for bioequivalence testing In vivo bioequivalence studies are required to ascertain the potential differences in bioavailability between innovator and generic products which, may lead to therapeutic inequivalence. A biowaiver provides the authority and grounds for fiscally intensive bioequivalence testing to be replaced by more tolerable in vitro testing. For the most part, IVIVC must first be established in order for a drug to be considered for a biowaiver. The BCS has outlined properties of solid preparations which require evaluation in biowaivers, i.e. solubility, permeability, and dissolution rate.35 In addition to this, the non-critical therapeutic range of a drug should also be considered35 and this is the basis for which paracetamol has gained biowaiver status.3 It should be noted that products produced by the same manufacturer at the same site are exempt from bioequivalence studies.36 6.1 Paracetamol Biowaiver Several characteristics must be considered when a drug presents as a candidate for a biowaiver through dissolution testing. Paracetamol is not a classic biowaiver candidate because it is classified as a BCS Class III drug, it does however possess properties borderline to Class I3 and these enable it to fulfill the requirements of a biowaiver. 6.2 Biowaiver requirements 6.2.1 Characteristics relevant to the active ingredient 6.2.1.1 Risk of therapeutic failure or adverse drug reactions i.e. the need for critical plasma concentrations. When considering a biowaiver for a drug substance, its therapeutic use and therapeutic index also needs to be taken into account.16 In the case of paracetamol, the therapeutic indications are not critical, and there is a wide difference between the usual therapeutic dose and toxic doses. Given that an optimal therapeutic dose for an adult is 1g, and that hepatocellular necrosis can result from ingestion of 10-15g, it can be assumed that paracetamol is not a narrow therapeutic index drug.3 6.2.1.2 Risk of bioinequivalence: Previous evidence of bioavailability problems for an active substance can complicate the justification of in vitro dissolution bioequivalence correlation.35 For paracetamol, the absolute bioavailability has not been shown to vary between therapeutic dose ranges of 5-20mg/kg.3 Other studies have also demonstrated that bioequivalence in different IR paracetamol preparations is achievable.11, 32, 37 6.2.1.3 Solubility: If a drug is highly water soluble it generally lends to exemption of bioequivalence testing, however polymorphism and particle size are major determinants of dissolution and must be considered.35 A drug is considered highly soluble if the amount contained in a preparation of maximal strength dissolves in 250mL of three buffered solutions ranging between a pH of 1-8 at 37C.35 Paracetamol has a pKa of 9.5 and is therefore not substantially ionized at a pH less than 9. As a result, it can be said that its solubility does not vary with pH.3 The highest strength IR preparation of paracetamol is 500mg. Experimentally, this has been shown to dissolve in 21mL,3 which is significantly less than the 250mL that is required by the BCS guidance to prove solubility.16, 35 6.2.1.4 Pharmacokinetic properties: High permeability which is typically indicated by a linear absorption pattern, reduces the potential influence of an IR preparation on bioavailability.35 For paracetamol, the permeability is slightly below the cut-off value of 90%, i.e. one study by Stewart et al.38 found permeability to be 80% once absorbed. This formally excludes paracetamol from being considered for a biowaiver, although extensions to BCS Class III drugs have recently been given more attention.20, 39 6.2.2 Characteristics relevant to the medicinal product 6.2.2.1 Rapid dissolution: Dissolution profiles can be regarded as equal when more than 85% of the active ingredient is dissolved within 15 minutes.35 This comparison must occur between test and reference product in three buffers which with a pH range between 1-8, at 37C.35 Paracetamol tablets have been shown to dissolve within 30 minutes,32 however this rate does not satisfy BCS exemption standards. 6.2.2.2 Excipients: Those included are to be well established and not in atypically large quantities. Kalantzi et al.3 details a table of acceptable excipients which can be used within paracetamol IR tablet formulations which are considered for in vitro dissolution biowaiver. 6.2.2.3 Manufacture: Critical parameters such as particle size and polymorphism should be addressed and documentation should be provided in the dossier that is submitted to TGA.35 Paracetamol has three metastable forms, the only commercially available from is the monoclinic acetaminophen as it is the most thermodynamically stable polymorph.3 From review of the literature, it can be concluded that in vivo bioequivalence testing of solid, oral IR paracetamol dosage forms may not be necessary. This can be justified given that a paracetamol formulation can be shown to:3 Rapidly dissolve under USP guidelines Contain only the acceptable excipients, in usual quantities Demonstrates dissolution profile similar to reference product under conditions stated in USP guidelines 7 Statement of Purpose 7.1 Aim hypothesis The purpose of the proposed study is to compare the dissolution profiles of bioequivalent IR paracetamol preparations listed on the PBS. In particular, comparisons between every preparation will be made, rather than a single comparison against a referent. We hypothesize that there will be no significant difference between the dissolution profile of IR paracetamol tablets when dissolved according to USP specifications. 7.2 Methodology We propose to analyse the dissolution profiles of eight PBS listed bioequivalent paracetamol preparations, namely; APO-paracetamol, Chemmart Paracetamol, Dymadon P, Febridol, Panamax, Paracetamol Sandoz, Paralgin, and Terry White Chemists Paracetamol. Sixteen tablets of each preparation will be dissolved in compliance with USP dissolution test for tablets and capsules, using apparatus II. As mandated, tablets are to be dissolved in 900mL phosphate buffer at a pH of 5.8 with a paddle set to 50rpm. Samples will be taken at intervals of 2,5,10,15,30,45,60 minutes in concordance with practice by Dominguez et al.34 these aliquots will be examined for paracetamol by UV spectrophotometry at 289nm. These data will be statistically analysed by ANOVA. 7.3 Timeline Date Tasks to be performed Work Deadlines Week 11 (15.03 21.03) Create paracetamol standard curves, Test expected dissolution time, Order materials, Source test tablets, Visit school of statistics for advice. Literature Review Due Monday 15th March 12pm Week 12 (22.03 28.03) Testing of tablets 1 2: Dissolution UV vis Week 13 (29.03 04.04) Testing of tablets 3 4: Dissolution UV vis Week 14 (05.04 11.04) Testing of tablets 5 6: Dissolution UV vis Week 15 (12.04 18.04) Testing of tablets 7 8: Dissolution UV vis Week 16 (19.04 25.04) Week in lieu to finish experiments in case of unforeseen circumstances Week 17 (26.04 02.05) Data collation statistical analysis Briefing on the writing of the final report Wed 28.04 2pm Week 18 (03.05 09.05) Writing draft report Week 19 (10.05-16.05) Editing final draft report Week 20 (17.05 23.05) Powerpoint presentation format 1st Draft Research Project Due Friday 21st May Week 21 (24.05 30.05) Correcting draft report Week 22 (31.05 06.06) Amending powerpoint presentation Final report due Mon 31.05 12pm Week 23 (07.06 13.06) Amending final report Week 24 (14.06 20.06) Presentation rehearsal Seminars, submission of amended report to pharmacy office

Comparing Satire in Canterbury Tales, Pride and Prejudice and The Rape

Use of Satire in Canterbury Tales, Pride and Prejudice and The Rape of the Lock Jane Austen and Alexander Pope had had a myriad of writing styles and techniques from which to express the desired themes of their works.   Satire, however, seemed to be the effective light-hearted, yet condescending, tool that enabled them to surface the faults and follies of their moral and elite society.   In Chaucer's Canterbury Tales, satire is used to the full extent in revealing the glutton within a pious and sacrificing nun, the vain hunter within a poor and meditative monk, and the vulgarity within a honorable woman of society.   In Pride and Prejudice and The Rape of the Lock, Austen and Pope use contrasting forms of satire to obtain the same result as Chaucer:   to ridicule society's hypocritical and supercilious   manner by forcing it to see the absurd truth of what society pretends to be and what it really is.   In order to create satire in their literature, Austen and Pope must place an ironic, mocking language in an environment, and allow the la nguage to transform its surroundings into a parody of human moral regression.   The essence of satire in Pride and Prejudice and The Rape of the Lock begins with the writer's mocking use of diction, and then spreads to how the characters, tone, and theme of the literature are heightened to a level that identifies with supercilious society.   Ã‚  Ã‚  Ã‚  Ã‚   Characters in Pride and Prejudice and The Rape of the Lock are necessary tools in establishing satire within the stories.   Austen uses a range of different character types in order to highlight the absurdity of society.   For example, Elizabeth Bennet differs greatly from her other sisters and young ladies of Hertfordshire because h... ...rning within society to undermine its flaws.   Austen and Pope were great writers and observers of their time, and though they have passed, their writings continue to reveal the hidden follies of humanity.   Humanity has not made any extremely valuable changes beside the obvious advancements that are expected through time.   However, there will always be literature to magnify humanity's growth and regression, urging its readers to never hide from the truth. Works Cited: Austen, Jane. Pride and Prejudice. Ed. Donald Gray. New York: W.W. Norton & Company, 1996. Chaucer, Geoffrey. The Canterbury Tales. Norton Anthology of World Masterpieces. Ed Mack, Maynard et al. W. W. Norton and Co. New York, NY. 1992. Pope, Alexander. "The Rape of the Lock". The Norton Anthology of English Literature. Ed. M.H. Abrams et al. 6th ed. Vol. 1. New York: Norton, 1993.