Patient Diagnosis: Lack of Energy Presentation

Patient Diagnosis: Lack of Energy Presentation Summary This dissertation is based on two patients who presented to medical services with a presenting complaint of a lack of energy?. My first patient, Mrs W, 61 years, has Diabetes Mellitus, type 2 and my second patient, Mr H, 59 years, has severe anaemia from unknown lower Gastrointestinal blood loss. I shall begin by focusing on the clinical aspects and basic medical sciences of their diseases and then go on to discuss psychosocial aspects, management, investigations and the role of professionals involved in their health care. I will then look at research and evidence based trials to explore the scope of their conditions and look at any current research that is being carried out. Throughout my dissertation I aim to reflect and convey what I have learnt and how I felt about my experiences. From writing this report I have developed as an individual and have gained personal advancements that I didnt expect to achieve. I have been able to widen my understanding of diseases and patients experience of their disease. Furthermore, I have gained an appreciation for research and evidence based medicine and developed a respect for other health care professionals. I have learnt the vital importance of taking on a holistic approach when dealing with a patient, rather than just looking at the basic science behind a disease. All in all, writing this dissertation has enabled me to truly understand how a disease can affect a patient and I now appreciate that it is not always about curing a patient, but about treating, advising and working towards a better quality of life for the patient and their family. 1. Introduction In my dissertation I aim to explain, explore and reflect on my experience of the People and Disease course. In particular I will focus on my experience of meeting with two individual patients with the same presenting complaint a lack of energy?. Both patients seem to be concerned with the prognosis of their disease but from very different points of view. My first patient wants to overcome her diabetes and not let it worsen; whereas, my second patient does not wish to know the cause of his anaemia, but is worried about the associated symptoms of his condition and how they will progress. Before contacting my first patient, Mrs. W, I felt apprehensive and quite anxious about the idea of having my own patient. I was worried about what she would think of me, how we would be able to build a rapport and what sort of questions I would ask her. In all honesty, I had naturally stereotyped her as a typical old lady?, but on meeting her, my initial thoughts were soon corrected. From this I have learnt that when given details about a patient you shouldnt necessarily stereotype and categorise them into a certain group in society. When asking her the initial questions that I had prepared I felt that it made the conversation very informal, so to adapt to the situation I just literally let her speak and tell me whatever she wanted to. This was very helpful to me as she had a lot of things she wanted to tell me and talk about. However, I do realise from communication skills seminars that not all patients will be as open as this in the future and therefore I do need to have the ability to speak to patients that are perhaps a bit more reluctant and unwilling to share their problems and thoughts. For example, you can use a lot of open questions to allow the patient to answer what they feel is comfortable for them and just gradually develop the conversation from what they say, rather than chit chatting?, which is what I found with my first patient. After asking Mrs.W about her recently diagnosed diabetes she seemed very unsure how to explain to me what she thought was wrong with her, she seemed to resent the fact she has a disease and questioned what she had done to deserve becoming ill. She said that even though the Doctor had explained everything to her, she was unsure of what to expect in the future and seemed quite worried about the aspect of not being able to care for herself. From telling me all of this, I felt quite overwhelmed and unsure of how to reassure her. Even though I wanted to help, I found myself in a situation where I physically couldnt, which was very frustrating. On my second and third visits I asked a bit more about her family situation, her social activities and her thoughts, ideas and feelings (psychological factors). From taking on this broader approach, I began to realise the true picture of Mrs Ws life and how it contributed to the worries of her illness. She told me about her husband leaving her and h er daughter and son becoming quite distant, she explained that she often felt lonely and at times it made her feel quite depressed. This seemed to be more of a concern to her than her actual illness, but it demonstrated why she is concerned about her diabetes worsening because she has very little family support and would have to cope by herself. From the meetings with Mrs W, I have learnt the vital importance of taking on a holistic approach when speaking to a patient. I have learnt that its not just a biological illness that contributes to the wellbeing of a patient; you have to take into consideration the home/family environment and the social and psychological factors. Not only have I had the opportunity to see an illness in the context of real life but I have greatly improved my confidence and patient communication skills by being able to gather information, take family history and cope in a one-to-one based home environment. However, my experience from meeting my first patient contrasted completely with my second patient experience. Initially I had some difficulties finding my second patient, as the consultant I had contacted only ran morning clinics; so I took the initiative to go into the hospital and find a suitable patient myself. Even though I felt quite nervous, I went onto the haematology ward and simply explained to one of the nurses about my course and what had happened so far with trying to find a patient. She was extremely helpful and understanding, which put me at ease and she more or less found me a patient right there and then (which I hadnt expected). However, even though I hadnt really prepared anything I already felt that I had developed some good skills and awareness of communicating appropriately with patients, both from my first patient and communication skills seminars, to be able to build up a good report with my second patient. Mr. H (my second patient) was very different to my first patient in the sense that he wasnt as open when talking about his illness. He is suffering from severe anaemia and has to have blood transfusions every week (so like my first patient, had the presenting symptom of no energy). However, he didnt seem to recall any dates of his illness and didnt want to explain what had caused the anaemia. However, after reading his medical records and meeting with his consultant, I came to realise that Mr. H had had a bad experience with a doctor and had adamantly refused further investigation, so his severe/worsening anaemia remains an unknown cause. Also, in comparison to my first patient, he had a much more considerable loss of energy, so even though he gave consent for me to talk to him, I felt at times he needed a break so I ensured that I did not stay too long and trouble him during my visits. Nevertheless, I found that meeting a patient in a hospital environment is completely different to meeting them in a home environment. In a hospital environment you need to be very aware of everything around you, how you are acting towards other staff and patients and there is a real need to realise certain cues from the patient (as they are in a more severe situation than a patient in a home environment). Overall, the People and Disease course has been a really enjoyable learning curve. Ive been able to put my communication skills to practice and see how to adapt to different situations, which has boosted my confidence enormously. Even though there is much more to learn, I really look forward to doing so and I hope that I will develop the skills needed to become a good doctor in todays society. 2. Clinical Features In this section I aim to discuss clinical features of my patients diseases and differential diagnoses. My first patient was diagnosed with Type 2 Diabetes Mellitus and my second patient suffers from severe anaemia; both of these conditions have similar clinical features and the same presenting complaint of a lack of energy and fatigue. Both of my patients recorded symptoms of lethargy, dizziness, fainting and shortness of breath; exploring these similar symptoms demonstrates the importance and accuracy needed for a diagnosis, as these symptoms could be indicative of a variety of other diseases. It is also vital to have a correct diagnosis, as a misdiagnosis would lead to unnecessary grievance, treatments or investigations which would cause a patient a lot of stress. Fatigue is the common presenting complaint in both of my patients and is clinically difficult to define; it is related to tiredness, exhaustion and a general lack of energy. Fatigue is a very common health complaint and around 20% of people in the United Kingdom claim to have fatigue intense enough to interfere with them having a normal life. Physical causes are estimated at 20-60%, and emotional causes are the other 40-80% (1).The fact that fatigue alone can disrupt ones life so severely indicates the important role of a doctor to be able to make a correct diagnosis for the cause of it. However, my individual patients described their fatigue in very different ways. Mrs W described her lack of energy in relation to feeling lethargic and very tired all the time, whereas Mr Hs fatigue was very much to do with a sudden onset of shortness of breath and chest pain. The symptoms that patients with anaemia normally present with are highlighted in the image below: (2) Mr. H has anaemia with haemoglobin levels often as low as 3.2gm/dL; with the normal range being 13 18 gm/dL for a male and 12 16 gm/dL for a female (2); indicating that his anaemia is very severe and therefore explains why he would experience fainting, chest pain and angina as shown in the image above. And in comparison to Mrs. W, highlights the difference in their experience of their clinical presentation of a lack of energy. Type 2 diabetes was previously referred to as adult onset diabetes and is related to insulin resistance and a relative, rather than an absolute, deficiency of insulin secretion (3). Due to the fact that this type of diabetes is concerned with gradual insulin resistance/deficiency means that individuals do not always (or initially) require insulin to achieve satisfactory diabetic control. The common symptoms associated with Type 2 Diabetes are (4): Polyuria: the need to urinate more often due to the body trying to excrete the extra glucose that is in the blood and in turn creating an osmotic gradient resulting in more urine production. Polydipsia: feeling thirsty more often than usual, due to the loss of fluids (increased urine production). Weight loss: this is due to the fact that glucose is not being taken up by cells due to insulin deficiency/resistance, so the body starts to burn up fat instead, which results in weight loss due to fat storage depletion. The majority of diabetic patients experience lack of energy because the cells in the body are not getting the glucose that they need, resulting in lethargy and tiredness. As type 2 diabetes progresses, patients may also experience blurred vision, yeast infections and prolonged time for wound healing. Mrs W was diagnosed with type 2 diabetes in February 2007; initially only experiencing a lack of energy. Over the months that I met with her she also started to experience polyuria and polydipsia. She was concerned as to how much her diabetes would progress and worsen because it had not been made very clear by her Doctor. This demonstrates the important need for a Doctor to be aware of patients concerns and level of understanding of their disease process. However, when speaking to Mr H about his clinical presentation and symptoms he had a very nonchalant attitude towards the cause of his disease. I later discovered that his anaemia was in fact due to unknown lower Gastro-intestinal (GI) blood loss and on questioning Mr H about this; he explained that he refused investigation to find the cause of the blood loss due to dissatisfaction with the way he was treated. He explained that during a scheduled procedure for a colonoscopy, the doctor carrying out the investigation was extremely rough and caused him a lot of distress and discomfort. And even though Mr H asked for the procedure to be stopped, the doctor proceeded against the patients wishes; this aggravated Mr H and led to violent behaviour towards the doctor and the dispute was later taken to court. I was very shocked to hear of his experience and also felt deeply concerned that he refused future investigations as his symptoms and anemia are very severe and have lead to angina and disabling conditions; with him being unable to walk and get out of bed unassisted due to such severe lack of energy. This emphasizes the crucial need for a good doctor-patient relationship, as shown in this case, without it, a doctor may be unable to make a proper diagnosis and prescribe ideal treatment.   Differential Diagnosis:- Diabetes:- The process of looking at a differential diagnosis involves weighing the probability of one disease against the possibility of other diseases accounting for a patients illness. For example, Mrs W presented with a lack of energy for her diabetes mellitus, but this complaint could have been diagnosed as any other kind of condition such as, hypothyroidism or Cushings disease as they can also present with fatigue. Differential diagnosis to Diabetes Type II:- Why is the condition considered to be a differential diagnosis How to make the correct diagnosis:- Hypothyroidism Also results in a lack of energy and fatigue. Often diagnosed via a blood test, examining the levels of T3,T4 and TSH in the blood. Cushings Disease Polyuria (and associated polydipsia); insulin resistance (especially common in ectopic ACTH production) (5)which can lead to hyperglycaemia (high blood sugar levels), which can in fact lead to diabetes mellitus. Dexamethasone suppression test or/and a 24hour urinary measurement of cortisol(6). Hyperglycaemia High circulating blood glucose levels this is a symptom of diabetes, but could also be due to physiological stress, critical illness or certain drugs. Blood test which indicates a glucose level of 10+ mmol/L (180mg/dl) also a test for diabetes, therefore, need drug/medical history. Anaemia:- The differential diagnosis of anaemia would be any condition relating to the presenting complaint of a lack of energy?, or any other condition relating to the symptoms of anaemia, as discussed in the clinical features section. In particular relation to Mr Hs lower gastrointestinal bleeding the differential diagnoses are as follows: Differential diagnosis for lower GI bleeding:- Why is the condition considered to be a differential diagnosis? How to make the correct diagnosis:- Haemorrhoids Swelling/inflammation of veins in the rectum commonly due to straining in constipation. These can often rupture and bleed. Physical examination of external haemorrhoids, digital rectal examination for internal haemorrhoids. Colorectal Cancer Cancerous growths in the colon (thought to be adenomatous polyps) can rupture, thus causing a bleed. Digital rectal examination, Fecal occult blood test (testing for blood in the stool), endoscopy (7). Ulcerative Colitis A form of Inflammatory Bowel Disease, includes ulcers and open sores which lead to constant diarrhoea mixed with blood. Endoscopy; involving both colonoscopy and sigmoidoscopy. From exploring the differential diagnosis of my patients conditions it has made me more aware of the vital importance of making the correct diagnosis; as there are a number of conditions that certain symptoms could be caused by. Furthermore, considering Mr Hs anaemia it does highlight the fact that his condition could be a number of quite serious conditions, which shocks me even more as he has chosen not to find out the cause of his worsening anaemia due to his troubled experience with a doctor. 3. Pathophysiology It is quite complex to discuss the aetiology of both my patients conditions as the exact cause of type 2 diabetes is not fully understood, although clear risk factors have been identified. Furthermore, Mr H refused investigation into his GI bleeding, which results in the cause of his anaemia remaining ambiguous. Diabetes Mellitus Type 2:- Diabetes Mellitus is a group of metabolic disorders characterised by chronic hyperglycaemia (high blood glucose concentration), due to insulin deficiency, insulin resistance, or both. There are two main types of diabetes; type 1 and type 2. They can clearly be distinguished by their epidemiology and probable causation, but not always so easily separated clinically. Type 1 diabetes is due to autoimmune destruction of insulin-producing beta cells of the pancreas therefore, causing an increase in fasting blood glucose. However, diabetes type 2 is a disorder that is characterised by high blood glucose due to insulin resistance and relative insulin deficiency (8). Since diabetes is a disease that affects your bodys ability to utilize glucose, it is important to understand what glucose is and how your body would normally control it. Glucose is a monosaccharide (simple) sugar that comes from the food we eat, cells take in glucose from the blood and break it down for energy; brain cells and red blood cells rely solely on glucose for fuel. The Pancreas:- The pancreas (where Insulin is synthesised) has both endocrine and exocrine functions. The exocrine function involves the secretion of digestive enzymes that are secreted from acinar cells and released into the small intestine via a system of ducts. Additionally, the endocrine part of the pancreas consists of millions of clusters of cells called Islets of Langerhans that produce hormones. Within the islets there are four main cell types; cells secrete glucagon, cells secrete insulin, cells secrete somatostatin, and PP cells secrete pancreatic polypeptide (9). Glucagon and Insulin are hormones secreted from the pancreas that work concomitantly to control the level of glucose in our blood. Glucagon is released when blood glucose levels fall, therefore resulting in stored glycogen being converted to glucose and thus increasing blood glucose levels, preventing a hypoglycaemic state. Insulin is a hormone that causes cells to take up glucose from the blood and store it as glycogen, thus a deficiency or resistance of this hormone will result in a high concentration of glucose in the blood. Insulin Release:- Beta cells release insulin via the following process; The glucose uptake takes place through a specific transporter protein called GLUT-2. The pancreatic ?-cell membrane contains several K+ channels, and two of them are directly involved, the K+-ATP channel and the maxi-K+ channel. The hyperglycaemia (high blood sugar level) accelerates the glucose uptake and metabolism and thus increases the ATP/ADP ratio. Increased ATP closes the K+-ATP channels, so the cell depolarises. During deploarisation from the normal resting membrane potential of -70 mV, a threshold is reached at 50 mV, resulting in the opening of Ca2+   channels. The Ca2+ influx triggers exocytosis of insulin and C-peptide containing granules following vesicular fusion with the cell membrane. ne. This process is demonstrated in the diagram below (10): However, in an insulin resistant individual normal levels of insulin that are released (via the process described above), do not have the same effect on muscle, adipose and liver cells, therefore resulting in glucose levels staying higher than normal. Increased levels of glucose in the bloodstream over a sustained length of time result in damage to blood vessels. Poorly controlled glucose levels can lead to complications such as nephropathy, retinopathy, neuropathy and cardiovascular diseases. Even though these complications may take a while to develop, it is important to realise that type 2 diabetes is often diagnosed at a relatively late stage. From looking at the pathophysiology of diabetes, Mrs Ws main symptom of lack of energy/tiredness can be explained. Due to her slow progression of insulin resistance means that more glucose remains in the blood and is not utilised by certain cells, such as muscle cells. Therefore, due to the fact that her cells are not able to use the glucose, she experiences weakness and tiredness. This lack of energy will progressively become worse and she may develop other complications if her diabetes is not controlled appropriately. Anaemia:- Anaemia occurs when there is a decrease in the level of haemoglobin in the blood and occurs when the production rate of red blood cells does not match the loss rate. It is a common condition in which all forms can be defined on the basis of physiological mechanisms. There are three broad categories: decreased/defective red blood cell production; increased destruction of red blood cells; and a mixture where both mechanisms operate simultaneously (11). Haemoglobin:- Haemoglobin is a substance contained within red blood cells and is responsible for their colour. It is composed of haem (an iron-containing porphyrin) linked to a protein, globin (12). Adult haemglobin consists of two and two globin chains. The iron containing porphyrin in the haem group is bound to each globin chain and a ferrous atom that can reversibly bind one oxygen molecule (as shown below (13). The biconcave shape of red blood cells enables a large surface area for the uptake and release of both oxygen and carbon dioxide. Haemoglobin becomes saturated with oxygen in the pulmonary capillaries where the partial pressure of oxygen is high and haemoglobin has a low affinity for oxygen (therefore, binds easily). Oxygen is then released in the tissues where the partial pressure of oxygen is low and haemoglobin has a low affinity for oxygen (therefore, oxygen offloads easily). The haemoglobin molecule itself exists in two conformations, relaxed (R) and tense (T). The tense state is characterized by the globin units being tightly held together by electrostatic bonds; when oxygen binds to the haemoglobin these bonds are weakened and broken, resulting in the relaxed conformation. The binding of one oxygen molecule leads to an increased affinity for the remaining binding sites, this is known as co-operativity, and is the reason for the sigmoid shape of the oxygen dissociation curve (below (14)). The binding of oxygen to haemoglobin can also be influenced by secondary effectors (as seen in the above image) i.e. hydrogen ions, carbon dioxide, and 2-3 diphosphoglycerate. The binding of 2, 3 DPG stabilizes the tense state and therefore, reduces haemoglobins affinity for oxygen (15). In conditions with lowered haemoglobin/oxygen levels, such as anaemia or hypoxia the concentration of 2, 3 DPG increases to raise oxygen availability for tissues. Haemoglobin Synthesis:- Haemoglobin is synthesised in a series of complex steps, it takes place in the mitochondria of the developing red blood cells. The major rate limiting step is the conversion of glycine and succinic acid to ?-aminolaevulinic acid (ALA), this occurs via ALA synthetase. Two molecules of ?-ALA condense to form a pyrrole ring, called porphobilinogen. The pyrrole rings are then grouped together   in fours, to form protoporphyrins. Iron is then inserted into the rings to form haem and then finally, haem is attached to the globin chains to form haemoglobin. Production and removal of red blood cells:- Red blood cells are formed and develop in the red bone marrow of large bones; the process by which they are produced is called erythropoiesis. The organ responsible for turning on the faucet of red blood cell production is the kidney. The kidneys can detect low levels of oxygen in the blood. When this happens, the kidneys respond by releasing a hormone called erythropoietin, which then travels to the red bone marrow to stimulate the marrow to begin red blood cell production. Within the bone marrow there are many stem cells from which red blood cells can be formed. As these cells mature, they extrude their nucleus and fill with haemoglobin, forming reticulocytes which can circulate around the body. After 3/4 months, approx 120 days, red blood cells begin to weaken and their cell membranes become very fragile. The red pulp of the spleen allows mechanical filtration and removal of red blood cells, and any leftover components i.e. iron from the haemoglobin are recycled to form new red bl ood cells (16). There are several different types of anaemia such as B12 deficiency, iron deficiency, diseases of the bone marrow and in relation to Mr H, chronic loss of blood. His severe loss of blood has subsequently led to his anaemia as there is a mismatch in production of red blood cells and loss of blood. Due to his deficiency in circulating reticulocytes, oxygen, via haemoglobin is insufficiently supplied to his body, resulting in severe lack of energy. Complications of his condition have led to shortness of breath and angina.   Angina Pectoris:- Angina pectoris literally means a choking sensation in the chest?. It is an episodic pain that is usually felt in the centre of the chest, often radiating to the neck and left arm. Angina occurs because myocardial oxygen requirement is greater than what it is supplied with. This results in a buildup of metabolites, causing pain (17). Classic angina occurs after exertion, excitation or emotion and is caused by insufficient oxygen supply to meet its demand; however, the pain normally subsides with rest. Due to Mr Hs chronic blood loss, there is insufficient blood supply to the heart and subsequent stress is placed on the organ which has led to his angina. 4. Psychosocial aspects of Illness and Disease The impact of chronic illness and disability is far reaching, extending beyond the patient to all those whom the individual has contact. Illness and disability affects all aspects of life, including social and family relationships, economic status, activities of daily living, and recreational activities. Even though several factors influence the extent of impact, every illness or disability requires some adjustment to everyday life. The extent of the impact can depend on (18): The nature of the condition Individuals pre illness/disability personality The meaning of the illness to the individual Individuals current life circumstances The degree of family/social support With reference to my patients, they each had different outlooks on their illnesses as mentioned previously. However, they do have certain similarities when considering the psychological aspect of their diseases. Both patients were shocked to find out their conditions as neither of them had expected to be diagnosed with a lifelong illness. This is known as biographical disruption, which is a key sociological concept as it identifies severe illness or disease as a major disruptive and unexpected experience. The illness/disease leads to a biographical shift from a perceived normal trajectory to an abnormal one, with the development of a new consciousness of the body, fragility of self and grief for a former life. For instance, Mrs W had future intentions to look after and care for her grandchildren and Mr H wanted to carry on working as a HGV driver; but due to their conditions they cannot achieve these former life plans and now have to adapt to a new ones. Additionally, they both explained to me how they experienced the feeling of facing stigma. Stigma refers to the identification and recognition of a negatively defined condition, attribute, trait or behaviour in a person or group of persons (19) . There are different types of stigma, such as enacted or felt. Mr H explained how he felt shunned from his friends and some relatives which refers to enacted stigma; the real experience of prejudice, discrimination and disadvantage as the consequence of his illness. Whereas, Mrs W spoke about her fear of being discriminated against and what people would think/say, which falls under a felt stigma; a fear of enacted stigma, also encompasses a feeling of shame associated with being diabetic?. I feel that this notion of facing stigma is perhaps underestimated in health care because it is not necessarily something a Doctor would automatically think about and therefore, perhaps wouldnt advise the patient on how to deal with such feelings. However, from talking to my patients about how they feel about having an illness they both stressed how psychologically disruptive it is, and how the feeling of being categorised as an ill individual has often led to depressive moods and anxiety. Therefore, from this experience I have learnt the importance of considering the patients thoughts and feelings rather than just focusing on how to treat their disease. Biological-psychosocial Model (Engel, 1977):- This is a model that incorporates psychological, sociological and biological factors in contribution to well being and health of an individual (20). It suggests that all three of these factors together and individually play an important role in relation to health and emphasises the importance of taking on a holistic approach when caring for a patient. The obvious factor of health is the biological factors of disease, the process of the disease and the individuals genetic make-up. Sociological factors include individuals family and friend support network as well as financial status and social class. Psychological factors include peoples disposition, their emotional status, whether they are stressed, depressed or anxious all contribute to ill health. From learning about this model it is important to note what factors affect a patient and how to deal with them accordingly when it comes to management and treatment of their disease. Both of my patients spoke of their psychological and social aspects and how they thought these factors had affected their illness. Mrs W, for example often felt quite depressed and lonely as she recently divorced her husband, and due to her illness often felt too tired to see her grandchildren. She also explained how she felt useless?, as she would get tired grocery shopping and house cleaning and she would get frustrated with herself, which often made her feel worse. This highlights how illness can be affected by more than just a biological aspect, and as a Doctor it is important to recognize other factors that affect a patients life. In comparison to Mrs W, who quite openly spoke about her psychological and social problems, Mr H was much more reluctant to tell me how he felt about his illness and how it was affecting him. However, over time I felt that he became much more comfortable talking to me and we were able to build a good rapport. He later went on to explain how he felt he had to keep a bravado about himself, being an ex army sergeant and that he was embarrassed that he often felt severely depressed and stressed about his worsening condition, but felt that by standing his ground and refusing investigation he Mechanisms Of Granule Formation: Pharmaceutical Industry Mechanisms Of Granule Formation: Pharmaceutical Industry For the production of solid oral dosage forms most fine pharmaceutical compounds require granulation to improve their flowability and processing properties prior to tabletting.    http://www.pharmamanufacturing.com/articles/2008/096.html http://www.scribd.com/doc/6601180/Tablet-Granulation Tablets are the most common drug dosage form today, and thus granulation, which allows primary powder particles to adhere and form granules, is one of the most important unit operations in drug manufacturing. Understanding granulation grows more complex each year. This article reviews the most current methods and mechanisms of pharmaceutical granulation, including factors that can lead to improved control. Particle-bonding Mechanisms a) Adhesion and cohesion forces in immobile films. If sufficient liquid is present in a powder to form a thin, immobile layer, there will be an increase in contact area between particles. The bond strength between particles will increase, as the Van der Waals forces of attraction are proportional to the particle diameter and inversely proportional to the square of the distance of separation [1]. b) Interfacial forces in mobile liquid films. During wet granulation, liquid is added to the powder mix and distributed as films around and between the particles. There are three states of water distribution between particles. At low moisture levels, the pendular state, particles are held together by surface tension forces of the liquid/air interface and the hydrostatic suction pressure in the liquid bridge. ADVERTISEMENT On Pharma Blog Get the latest analysis and commentary on manufacturing and the drug industry at our editors blog. On Pharma looks at the drug industry with a special focus on manufacturing, which is coming into its own as a strategically important area. When all the air has been displaced from between the particles, the capillary state is reached, and the particles are held by capillary suction at the liquid/air interface. The funicular state represents an intermediate stage between the pendular and capillary states. Moist granule tensile strength increases about three times between the pendular and the capillary state. These wet bridges are, however, a prerequisite for the formation of solid bridges formed by adhesives present in the liquid, or by materials that dissolve in the granulating liquid. Solid bridges can be formed in two ways: Hardening binders. When an adhesive is included in the granulating solvent it forms liquid bridges, and the adhesive will harden or crystallize on drying to form solid bridges to bind the particles. Crystallization of dissolved substances. The solvent used to mass the powder during wet granulation may partially dissolve one of the powdered ingredients. When the granules are dried, crystallization of this material will take place and the dissolved substance then acts as a hardening binder. c) Attractive forces between solid particles. In the absence of liquids and solid bridges formed by binding agents, there are two types of attractive force that can operate between particles in pharmaceutical systems, electrostatic forces and Van der Waals forces. Van der Waals forces are about four orders of magnitude greater than electrostatic and add to the strength of granules produced by dry granulation. Mechanisms of Granule Formation a) Nucleation. Granulation starts with particle-particle contact and adhesion due to liquid bridges. A number of particles will join to form the pendular state. Further agitation densifies the pendular bodies to form the capillary state, and these bodies act as nuclei for further granule growth [2]. b) Transition. Nuclei can grow in two possible ways: either single particles can be added to the nuclei by pendular bridges, or two or more nuclei may combine. The combined nuclei will be reshaped by the agitation of the bed. This stage is characterized by the presence of a large number of small granules with a fairly wide size distribution. c) Ball Growth. If agitation is continued, granule coalescence will continue and produce an unusable, over-massed system, although this is dependent upon the amount of liquid added and the properties of the material being granulated [1]. There are four possible mechanisms of ball growth, which are illustrated in Figure 1 [3]: Coalescence. Two or more granules join to form a larger granule. Breakage. Granules break into fragments which adhere to other granules, forming a layer of material over the surviving granule. Layering. When a second batch of powder mix is added to a bed of granules, the powder will adhere to the granules, forming a layer over the surface and increasing the granule size. Abrasion Transfer. Agitation of the granule bed leads to the attrition of material from granules. This abraded material adheres to other granules. Granulation Methods  [4] Dry Granulation. This requires two pieces of equipment, a machine for compressing the dry powders into compacts or flakes, and a mill for breaking up these intermediate products into granules. The dry method may be used for drugs that do not compress well after wet granulation, or those which are sensitive to moisture. Wet Granulation. In this method, the wet mass is forced through a sieve to produce wet granules which are then dried. A subsequent screening stage breaks agglomerates of granules. Organic solvents are used when water-sensitive drugs are processed, as an alternative to dry granulation, or when a rapid drying time is required. Because direct compressing is not the best technology for many active substances, wet granulation is still a preferred method. Even if the active substance is sensitive to hydrolysis, modern equipment (e.g., a fluidized bed) eliminates all problems in wet granulation [2]. http://www.investopedia.com/terms/l/leptokurtic.asp Dawar Qhoraish (k0920236) Nazmul Islam (k) Introduction Granulation can be used to For the production of solid oral dosage forms most fine pharmaceutical compounds require granulation to improve their flowability and processing properties prior to tabletting.    Method and Materials The experiment was carried out as explained in PY2020A practical booklet, without any amendments. Paracetamol (25g), lactose (265g) and sodium starch glycollate (2.945g) and PVP solution 15% (30ml) was used. 1 Erweka AR402 oscillating granulator with the finer sieve was used to granulate the drug without too much force with variables of turns (rpm) and time (minutes). The machine had an emergency switch off button and safeguard on top which turns off machine when you put your hand in. Sieve shaker used was Retsch A5 200 basic was used to separate the particles into different sizes by vibration with variables of amplitude and speed. The top sieve was fixed by parallel bars with screws and bottom of sieves contained rubber bands to control any overflow and stability. Discussion Modal: Low so most particles are fine. (low) Relate to flow rate. Better flow rate. Small IQR-data close to each other. Positive skewness means more particles with finer particles, so flow rate is better. What Does Leptokurtic Mean? A description of  the kurtosis in a  distribution in which the  statistical value is positive. Leptokurtic distributions have higher peaks around the mean compared to normal distributions, which leads to thick tails on both sides. These peaks result from the data being highly concentrated around the mean, due to lower variations within observations. Limitations: 7.9% MC was lost after 45 minutes in 75oC oven compared to 9.51% in 130oC heater balance. Tray was exposed to air for different amount of periods each time, errors as tray was allowed to cool down. Not dried properly Granulators normally used for large quantities. If lubricant used, particle size would be higher. Improvements: More repeats, heat for longer and at high temperature.