Environmental Issues Essay Example | Topics and Well Written Essays - 1250 words - 2

Environmental Issues - Essay Example Handling temperatures and pressures of subsea oil can easily be monitored through the use of sensors and other instruments even during drilling (p. 135). But Rose argues that even though modern technology, research and monitoring systems have reduced the frequency of ecological catastrophes, still, there are factors that can cause oil-well blowout from high-pressure and high-temperature which can result to emission of buoyant plume of oil, producing water and methane (p. 141). Baird stated that â€Å"hurricanes have become manageable, with oil lines now being capped at or beneath the ocean floor† (p. 135). But aside from oil lines on and beneath the ocean floor, Rose said Hurricanes Katrina and Rita destroyed 115 platforms, spilling roughly 17,700 barrels of petroleum and 25,110 barrels of mixed crude oil from above-ground storage tanks in Louisiana (p. 141-142). Petroleum leaks, Baird said, can now be restrained by industrial seals (p. 135). Although this is the case, the pro blem does not stop at petroleum leaks. Rose argues that another disturbing impact of offshore oil is the volume and type of wastes, such as produced water, drilling fluids, cuttings, diesel emissions, and chemicals associated with operating mechanical, hydraulic, and electrical equipment (p. 142). Even with modern technology, we cannot guarantee that offshore drilling can withstand the force of God, which include hurricanes and other natural disasters, and human errors. Modern technology cannot reverse the destructive environmental impacts of offshore drilling gone wrong. It is better for us to find alternative sources which are safer for the environment and for the people’s health. Protecting the environment does not mean we are less concerned about protecting the country from economic problems, but other alternative sources can lower oil imports and thus save our country from further spending. Issue 8 - The release of carbon dioxide in the atmosphere contributes to global w arming and is thus a danger to the well-being of human beings. To ease global warming, either people refrain from using fossil fuel as an energy source or capture carbon dioxide before it reaches the atmosphere (Easton, 2011, p. 148). In carbon capture technology, the debate is not about the existence of the said technology but on their sustainability, safety and viability in being stored underground indefinitely (p. 149). In a nutshell, there are three issues surrounding the debate between David Hawkins and Charles Schmidt – the availability of technology, safety concerns and the political will to end the use of coal (Easton, 2011, p. 149-150). Hawkins maintains that the technology to capture carbon emissions are already existing and can already be utilized while Schmidt contends that the available technology is not yet technically and financially viable to be utilized in a major scale (p. 149). Anent to this issue is the question on safety, while Hawkins maintain that the t echnology on safety concerns are already feasible, Schmidt contends that there is still no assurance that carbon dioxide can be stored and can remain in containment underground indef

Ford's future Essay Example | Topics and Well Written Essays - 750 words - 1

Ford's future - Essay Example Its North American automotive business is hemorrhaging cash and market share† is the comment by Bryce G. Hoffman from Detroit News. The fall of the empire of Ford is evident from the fact that Fords domestic brands -- Ford, Lincoln and Mercury -- saw their combined share of the U.S. market fall 4.7 percent last year, from 18.3 percent in 2004 to 17.4 percent in 2005. A decade earlier, Fords market share stood at nearly 25.6 percent. Every percentage point of market share represents 170,000 vehicles. With this background this paper aims at analyzing the factors that led Ford to reach this no-alternative ‘Way forward’ position and the likely impact of the decision to cut jobs and close manufacturing facilities on the future of Ford. The financial results for the year 2006 would be the worst in the 103 years history of Ford. The old record net loss of $ 7.39 billion would be surpassed by the loss for the year 2006 as already the loss is mounted at $ 7 billion for the first three quarters of 2006 and for the fourth quarter more losses are expected by the analysts. The financial situation of Ford was worsened by the collapsing sales of its F series Pick up and truck based sport utility vehicles in which segments the company made huge losses. New product investments -- utilizing Fords global architectures and scale -- to deliver more new products faster, including more crossovers, hybrid vehicles, new small cars, increased spending on Fords truck leadership and new "white space" products. A lean and flexible manufacturing system combined with capacity matched to demand. Capacity will be reduced by 1.2 million units or 26 percent by 2008, representing the majority of actions within the plans 2006-2012 periods. In order to give life to the restructuring plan, Ford mortgaged nearly all of its domestic assets- its plants, office buildings, patents and trademarks — along with stakes in Ford Credit and Volvo, to raise $18 billion. Ford said its restructuring

Political Philosophy - What is the best form of government Essay

Political Philosophy - What is the best form of government - Essay Example Plato’s argument against democracy is dependent on the basis of it being centered on the power of the people to decide what they deem is good for them. The problem of the lack of specialization on matters of the state poses a problem on the choosing of the best possible solution. The Greek word ‘demos’ which translates to ‘the people’ is easily attributable to the concept of ‘the mob.’ This is where the concept of the silent majority and the loud minority may come to play. The word mob by itself sends a negative connotation that can be thought of as unruly and chaotic. Plato proposes that a leader should be holistic in his education and approach to ruling the state. Foremost, he must be a philosopher as Plato thinks that this enables him to consider the importance of education for others. There are also other requirements which include knowledge in music, mathematics, military, and physical education. The analogy of a person’s heal th to a state directly explains why Plato does not favor democracy. The state and its health need to be attended to be by a doctor (Wolff, p. 67). A physician will be able to administer with skill and accuracy correct judgment because of his expertise. This in essence undermines the capacity of the people to articulate good views. Mills idea of democracy is very straightforward, â€Å"to improve the citizens, and to manage their public affairs. Thus governments are to be judged by their effects on individuals, whether they improve them morally and intellectually, and by their efficiency in dealing with matters of public concern† This essentially means the need for representation and the importance of the power of the constitution becomes tantamount. People thrive when they are given independence. Everyone plays a part in the realization of sovereignty by being protective against the danger of oppression (p. 94-95). Rousseau’s proposition is not so different from that of Plato

WEEK 4 DQ 7 Assignment Example | Topics and Well Written Essays - 250 words

WEEK 4 DQ 7 - Assignment Example Legitimate, coercive and reward as forms of formal power. Personal power deals more with what other individuals see and regard of someone they respect or like, thus giving someone the ability to influence. Expert, information and referent power have been classified as personal power. An example of an unethical use of power was when I was instructed by my superior to perform a task that was supposed to be his. In this case, my superior exercised his formal power, and was able to influence me to do the work for him. My superior unethically used legitimate power over me, emphasizing that I should be the one following the orders. Such scenarios I believe are common in many organizations where the people in authority tend to abuse the power accompanied in the positions they fill in. Political behaviors are actions with which an individual or a group of individuals make to be able to influence others in the organization to get the result they want. The three dimensions of political behavior are: upward influence, downward influence and peer influence. Upward influence refers to the capability of the people at the lower level of the organization to influence the decisions of the people with authority in the organization. Downward influence is the capacity of a superior to influence those under his or her department, such as general managers influencing department managers and their subordinates. Peer influence is the most common and this usually occurs with people who are in the same level of the organization. In laymans term, this may also be seen as peer pressure. However, this kind of influence may be destructive if there is no common goal among the people involved. Individual and organizational antecedents greatly influence political behavior. Political skill, investment in organization, internal locus control and expectations of

India’s Classical Age Essay Example | Topics and Well Written Essays - 250 words

India’s Classical Age - Essay Example It is believed that Kalidasa was one of the nine gems in the court of the great Vikramaditya. Therefore, it is evident that some influence of the socio-political elements of the period can be traced in the plot of the great drama as no literature is free from the local and contemporary social influences. The great drama by Kalidasa, in the similar fashion, captivates the rich and glorious heritage of India and its tradition. We come to know that kings were fond of hunting and as the opening scene shows the king set out for hunting and chasing the antelopes, Sakoontala indeed is a great material to be incorporated as a film. The plot of the drama and its narrative structure captivates great dramatic element. Along with that character portrayal and character development of the drama give the play a total cinematic dimension. All the characters are portrayed brilliantly and coherently for the support of the plot and its development. A thorough focus on the main characters that of Sakoontala and Dushyanta launches its readers to a better understanding of the play incorporated as a film. The tender and innocent Sakoontala at the lap of nature falls in love with the king. Her love is fresh and pure as the nature. Amid the charm of the nature and enchantment of the nature girl Sakoontala, the king is enamoured in the love of the nature and the young tender girl with the ferocity of lightening and charm of an antelope. But their departure and the trajectory which the tender girl from the lap of the nature, Sakoontala undertakes launch her to a n evolved character of a matured fighter of her social rights and give a complete coherence to the plot and trajectory of the character development. On the other hand, the character transformation of Dushyanta, the king also is worth appreciation. His journey from falling in love to forgetting it and finding the lost love once more supports the plot development and trajectory of Sakoontala’s character equally

Global warming effects Essay Example for Free

Global warming effects Essay Yankee Candle Company began in 1969, as penniless Mike Kittredge, age 16, melted crayons to form a candle as a Christmas present for his Mom. A neighbor, mesmerized by his fabulous creation, expressed her desire to purchase one of his candles; thus Yankee Candle Company was born. Mike used his parents basement, kitchen, and garage to produce his scented candles. Five years later, in 1974, Mike moved production into an old paper mill located in Holyoke, Massachusetts. In 1998 Forstmann Little Company partnered with Yankee Candle Company and began to publicly trade on the NYSE in 1999. Mike Kittredge sold his first candle to a neighbor for $1.36, in 1969 and in 2005 Yankee Candle Companys total sales were $601,180,000. Mikes humble beginning in the family home has grown into a wholesale customer network of 16,400 store locations, a growing base of Company owned and operated retail stores (390 located in 42 states),†¦ direct mail catalogs, its website,†¦ international distributors, and to a European wholesale network of approximately 2,200 store locations†¦ (2006) Yankees passion for fragrance has become a profitable entity with visions of continued global expansion. Yankee Candle Company has branded their product as long-lasting and strong in fragrance. Yankee has developed over 150 fragrances for their various candle products. Their product line includes jars, votive, tarts, wax potpourri, pillars, tapers, and tea lights candles. Yankees design is innovative and their scents are pleasant, relaxing, and rejuvenating. Yankee Candle Companys design department is visionary in developing candles to accent modern dà ©cor and fragrances that appeal to its customers. Yankee will explore and introduce aromas that are common to the Greek culture as they expand into this new market. Yankee Candle will emulate their passion for fragrance and provide a wide variety of choices for its new customers in Greece. The Yankee Candle Company continues to build on the passion and creativity of Mike Kittredge; driven by a mission to warm hearth and home with the fragrances of life through excellence, innovation, and passion. Yankee has been dedicated to excellence throughout their 37 year history. A company spokesperson attributes their success to, our vertically integrated  business model, which enables us to control most every aspect of our business, from product development to manufacturing to distribution to marketing and sales. This structure allows us to consistently provide high quality and innovative products†¦ (2006) Yankees innovation is evident in their candles and accessory designs, which acclimate too various dà ©cor preferences and the expanding variety of fragrances, which appeal to its customers. Yankee Candle Company is driven by an intense passion to spread the fragrances of life around the world for all to enjoy. The product expansion into the Greek marketplace is another step towards reaching their objectives. Yankee Candle Company will expand its fragrances to blend in with the cultures of new markets. Yankee will continue to develop partnerships with established Company owned retail stores as venues for their products to be sold. The candle company has already established Yankee Candle  ® Europe with a 30,000 square foot distribution center in Bristol, England that provides Yankee products for approximately 2,200 stores. This distribution center will be used to export Yankee products to be sold by retail stores in Greece. The Yankee Company has decided to expand their markets and head out to the Country of Greece. We will be exporting our candle line product from the United States to Greece. The product expansion into the Greek marketplace is another step towards reaching their objectives. Yankee Candle Company will expand its fragrances to blend in with the cultures of new markets. Yankee will continue to develop partnerships with established Company owned retail stores as venues for their products to be sold. As Yankee Candle expands into new regions of the world, distribution centers will be built to service their wholesale store network. Where trade barriers, economical and political policies will allow. When expanding into new countries, Yankee Candle will establish an online shopping website to market and sell their products. Since 1994, the United States is part of the NAFTA organization between three countries. The North American Free Trade Agreement, known usually as NAFTA, is a free trade agreement among Canada, the United States, and Mexico. NAFTA  went into effect on January 1, 1994. NAFTA is also used to refer to the tripartite trading bloc of North American countries. www.wikipedia.org. Since the inception of the Eurpeon Union in 1957 six countries were a part of this union. Nineteen further states have joined in and creasted a successful union. Greece joined the EU January, 1981. The exchange and repatriation of funds risks the Euros exchange rate against the dollar, remains unstable. The low interest rates, increased competition in the banking industry, and continued growth in commercial bank lending; to raise bad debt and strong growth in consumer borrowing. Economic growth is forecast to slow in 2006 and 2007. The consumer price inflation slowed dramatically in Greece before its entry into pre-economic and monetary union (EMU) in January 2001 and was helped by other temporary measures. The economy of the United States is stable made up of natural resource, labor and manufacturing, and investments. The United States has the largest and one of the most technologically advanced national economies in the world, with a GDP of 13.049 trillion dollars. www.wikipedia.org. Consumers and producers have some decision-making that form the economy, but the government also has a powerful role on the effects of the economy. The economy of Greece is growing fast after the implementation of stabilization policies in recent years. Greece remains a net importer of industrial and capital goods, foodstuffs, and petroleum. Leading exports are manufactured goods, food and beverages, petroleum products, cement, chemicals, and pharmaceuticals. www.wikipedia.org. Greece is global leader in shipping, which is the transportation of goods and cargo by land, air, or sea. Types of currency used through out the world vary from country to country and or by region. The Unites States of America official currency is the dollar, symbol: USD also known to be abbreviated by $. The US currency was adopted in 1785 by the United States Congress. The United States dollar is also known as a world currency; in 1985 $300 billion dollars were in circulation,  with two thirds being out side of the Untied States. Each year the amount of U.S dollars is being circulated around the world continues to increase. In comparison to the Untied States of America, Greece uses the euro as denomination of currency type, symbol â‚ ¬. Greece is part of the European Union also knows as the EU. What I found most interesting is the European Monetary Union has ceded control of monetary policy to the European Central Bank. Versus the Untied States taking control over their own currency. The European Union has a large economy, probably slightly larger than that of the United States of America with a 2005 GDP of 12,865,602 million vs. 11,734,300 million (USD figures) (using nominal US Dollar GDP) according to the International Monetary Fund. www.wikipedia.org. Greeces relations with other countries in the region have been steadily improving. Greece is working with Turkey to resolve their disagreements, mainly with regard to Cyprus. Failure to resolve the division of the island of Cyprus may increase tensions between Greece and Turkey as the latter finds its bid to join the European Union partially dependent on success, but tensions rise sharply with Turkey over the issue of Cyprus. Greece is also assisting and improving relations with the economic development of the Balkans. The Balkans is now viewed by Greece as a greater threat to security than Turkey. Also, renewed instability in the Balkans leads to unrest in Greece and trade disruption. Political corruption is considered higher in Greece than many other European Union countries. Politicians are dependent on media with strong ties to business interests. There is a politicized, anti-globalization environmental movement in Greece which is increasingly complicated in its use of the courts and the European Union to block large projects. United States culture is very diverse but due to the level of the American culture there are many integrated but exclusive subculture within the U.S. The subcultures differentiated by status, ethnic background, residence, religion or other factors that functionally combine the group and act jointly on each subculture member. The ethnic groups are White, Black, Asian, Amerindian, Alaska native, native Hawaiian, and other Pacific  islander. The various religion are Protestant, Roman, Catholic, Mormon, Jewish, Muslim, Baptist, and others. Lastly, the languages are English, Spanish, Indo-European, Asian, Pacific island and others. Let us not forget that the government type is constitution-based federal republic but strong democratic tradition. As a result, the subcultures have their own joint set of customs, attitudes, and values. Greece is a diverse culture partial by its place at the crossroads between the East and the West and by the various occupations endured by the Greek people throughout history. The Greeks are proud of their culture which is the definition of their national and ethnic belonging. The Greeks culture is made of their traditions, religion, music, language, food and wines. Some of the traditions and superstitions vary from one island to another. Many countries differ within a range of dimensions including social structure, language, religion, and traditions to name a few. The difference has important implications on marketing strategy of the product. The most cultural difference that has an impact would be traditions. Candle scent preference may differ from one country to another. The company may encounter resistance to some of its different scents or wax. The organization must careful research Greece cultural norms and understanding the difference between US and Greece. Cross-Cultural training (literacy) would be needed to make sure the company advertising or marketing strategy does not offend anyone in the other country. The candles should be affordable due to the unemployment rate within Greece; however the organization must make a profit consider the cost to export the candles within that country. Yankee Candle is aware of the culture difference between the US and Greece, therefore staffing would be important to the organization. The organization would provide their US employees with language and cultural training. Yankee understands that one of their vendors Berlitz has experience and knowledge in cross cultural and language training that would help assist the expatriates. Berlitz offers a variety of programs and has been in the  business for 128 years, more than 450 centers in over 60 countries. Berlitz offers online, adult, children and teen programs for cultural and language training including one-on-one sessions. The cultural and language training would be for the family as well. The cultural training would be for two days and 100 hours for language training, however if more hours are needed for language the company would approve this cost. The employees that are going on the international assignment would have other benefits including when they are expatriating back in to the US. However, the expatriates will receive just a  ½ day of cultural training and language will not be necessary. The US dollar is not equal to the same amount in most other countries. Hence, the company would pay an additional allowance to cover the difference. The cost of living may be higher in the other countries, as a result a housing allowance is provided to the employee. The company does consider the cost living in the US and then compare that cost to living in Greece. The education in Greece is not the same for US citizens. As a result, to the language barrier and cultural it may be very difficult for the employees children to attend the local school in the host country for that reason private schools or boarding school may be required. Consequently the company is aware of this and therefore would provide tuition allowance. Due to the cultural and language difference there are going to be diversity issues, so human resource has provided an open door policy. The open door policy would allow employees to express him or she concerns and human resource will try to provide a solution to the problem, if possible. Supply chain management is an important role for the success of Yankee Candle Company to sell scented candles in Greece. Supply chain is most effective for optimal resource use, minimum total cost, and maximum value to the customer. Decisions with in supply chain are to buy your product or make your own. Yankee Candle Company already produces its own scented candles and will be the same for candles being shipped overseas. The production will be manufactured in the Companys 294,000 square foot facility in Whately, Massachusetts. As a manufacturer, the Company is able to closely monitor product quality and control production costs, which ensures high quality  products and maintains affordable pricing. Information has been gathered from the Greece from the candle business industry. This data will assist in forecasting how much product is needed for a three months supply to meet the supply and demand in Greece. Lead time for the initiation of Yankee Candle Company to enter the Greece market is 10 months. In turn this will give enough time to meet the three month stock supply. The information gathered from the Greece candle market will support the types of scented candles that will be produced to ship overseas. Lead time for the shipment to arrive at the distribution warehouse is three months; the life span of a candle is three years. Placing our product will be near or around the largest cities and ports in Greece. The largest and most important city in Greece is Athens, the capital with population based in 1991 of 748,110. The largest port in Greece is Thessalonà ­ki, with a population of 377,951. Also another large port is located on the North part of the Peloponnesus, is a major seaport, with 155,180 inhabitants. Other sizable cities include Là ¡risa (113,426), Irà ¡klion (117,167), and Và ³los (76,463). The ports and its population are important factors in knowing were to place the Yankee Candle Stores. These would be in areas in the region that have the most population and are easily accessible to Tourist from vacation boats that may doc on these ports. Promoting Yankee Candle Company in Greece would be similar as it is currently in the Untied States. Through its retail stores the Yankee Candle company would open in Greece, direct mail catalogs. To include a large market Yankee candle will also promote is U.S product through television commercials newspapers, bill board singes through out the larger cities of Greece, and through its own web page http://www.yankeecandle.com/cgi-bin/ycbvp/retail.jsp. Promotion for this product will be introduced to all who wants to have special fragrances in their homes. Business will also be targeted to have fresh new fragrances for their offices. Candles are an excellent gift for all ages and for any special occasion. The middle class in Greece is the main target market Yankee Candle Company is promoting the scented U.S candle product. In 2005  the labor force in Greece was at 4.72 million compared to unemployment rate of 10.8% figures from www.cia.gov. These figures give Yankee Candle Company the green light to proceed with international distribution into the Greece market. Pricing the candles will be 30% above the sale price of a U.S product. This will ensure the costs of having a U.S product of seas. Yankee Candles has successfully developed and market new products and earn enormous returns. We have success springs for the fact that it has a vertically integrated business model, with the in-house expertise required to design, develop, manufacture, distribute and sell our candle products. Our vertically integrated business model acts as a powerful platform to support our product innovation initiatives. This business model included strong research and development activities, an experienced employee team, and a basis skill in test marketing our products. We collected these resources to research consumer interests and home decor buying trends, and then to create original candle designs, fragrances, accessories, gift sets, home fragrance merchandise, and personal care items that align with our findings. We then release this merchandise into our distribution channels in a way that permits us to seek and track consumer feedback. This process positions us to fine-tune our new products from performance, to packaging, to labeling, to pricing helping to maximize the potential for each item we develop to have a successful launch and widespread acceptance. Together, these efforts helped to drive sales, attract new customers and extend the appeal of the Yankee Candle brand. Once exporting was chosen as the mode of entry, Yankee Candle secured assistance from a company called, Export Trade of America; to learn about insurance, tariff, and tax laws involved in trading with Greece. Yankee Candle Company will face various legal challenges when exporting its candles into Greece, but the process will go much easier with the help of an export management company. Yankee will need to comply with employee laws and have knowledge about hiring, firing, and discipline regulations in Greece. They will need to be acquainted with their legal system and how those laws are enforced. Greece is a parliamentary republic with a president, who is heads the executive administration, a prime minister, who is head of the  government, and a 300 seat legislature. The judicial includes a Supreme Court, regional districts, and prefectures to decide civil and criminal cases. There is a national police force as well as policing agencies from the European Union. As a member of the European Union, the EU laws supersede those of the individual member nations. Yankee Candle Company will need to be aware of the EU laws, enforcement, penalties, and necessary trade practices. The European Union could cause legal complications as the union adds new members, arbitrates disagreements among its memberships, and as competition increases in the global marketplace. There has been a longstanding relationship between Greece and the United States of America. The two countries have diplomatic, intelligence, and law enforcement ties. Greece and the United States, recently signed treaties covering extradition and mutual legal assistance, which further strengthened this cooperation. (2006) Trade between these two nations should proceed with success barring increased terrorism, war, or a terrific natural disaster that impacts the global economy. It is important for any company to evaluate their strengths, weaknesses, opportunities, and threats. As Yankee Candle employees examines their organization they listed the following as company strengths; strong business model, long-lasting candles, well-branded product, variety of fragrances, adaptability of product to various cultures and dà ©cor, strong financial backing, increasing profitability, expanding marketplace, efficient manufacturing and distribution process, and an innovative product development. Yankee Candle Companys weaknesses include; rising cost for manufacturing and distributions, technological skills, single manufacturing center, adapting products to various cultures and customs, and material shortages. There are several opportunities that must be pursued to maintain profitability; increase presence in the global marketplace, expanded online shopping options, adapt fragrance choices to new markets, build foreign manufacturing and distribution center, and add accessories to their product line. There are many threats to the existence of Yankee Candle Company  including; competitions pricing and product differentiation, terrorism, natural disasters, exchange rate, rising costs for manufacturing and distribution, and the products life-cycle. The external environment strengths include; reduction in trade barriers, strong European Union, technological advancements, and utilization of websites. The external weaknesses are; trade blocs, closed economic and political policies that prevent or limit imports/exports, and the affects of terrorism. External opportunities include; improving the economic levels of third world countries, utilizing the skills, resources, and expertise of various countries to lower costs and create an integrated economy, develop innovative products, and create a global network. Finally, the external threats include; terrorism, political instability, natural disasters, increased global competition, trade blocs that become fortresses against those outside their union, countries imposing regulations against outsiders who want to merger or acquire other foreign companies, conflict among existing trade bloc members, and inflation/deflation of the monitory systems. Reference: (2006, 4,12). The Yankee Candle Company, Inc. 2006 First Quarter Earnings Webcast. Retrieved 4/23/06, from SBC Yahoo Finance Web site: http://biz,yahoo.com/bw/060412/20060412005002.html?.v=1www.wikipedia.org., retreived April 24, 2006. http://www.cia.gov/cia/publications/factbook/geos/gr.html#EconRetrieved 5/13/06 from the World FactbookUnknown, Retrieve on April 23, 2006 fromhttp://www.odci.gov/cia/publications/factbook/print/gr.htmlUnknown, Retrieve on April 23, 2006 fromhttp://www.greeka.com/greece-culture.htm

Colon Specific Drug Delivery

Colon Specific Drug Delivery ABSRACT The colon is a site where both local and systemic delivery of drugs can takes place. Colon specific drug delivery has achieved importance for the delivery of drugs for the treatment of local diseases associated with the colon like crohn’s disease, ulcerative colitis etc. as well as for the systemic delivery of proteins, therapeutic peptides, antiasthmatic drugs, antihypertensive drugs and antidiabetic agents. A drug need to be protected from degradation, release and absorption in the upper part of GIT and then to be ensured abrupt and controlled release in the proximal colon. This article reviews a detailed study about need of colon specific drug delivery, limitation and challenges, factors affecting colonic drug delivery, different approaches of colon including some successful novel approaches such as CODESTM, Pulsinicap system, Port system, Colal pred system, Multiparticulate system and also a study on evaluation for site specific drug delivery to colon. INTRODUCTION Drug administration through an oral route is the most convenient and important route of administering drugs for systemic effect. At about 50% of the drug delivery systems available in the market are oral drug delivery systems and these systems have more benefits due to patient acceptance and ease of administration. During the last decade considerable interest has been given in developing site-specific formulations for targeting drugs to the colon. Colon specific drug delivery has achieved increased importance not only for the delivery of the drugs for the treatment of local disorders associated with the colon like Crohn’s disease, ulcerative colitis, irritable bowel syndrome and constipation but also for the systemic delivery of proteins and peptides, antihypertensive drugs, antiasthmatic drugs and antidiabetic agents. The colon specific drug delivery system should have capability to protect the drug en route to the colon i.e. drug release and drug absorption should not occur in the stomach as well as the small intestine, and the bioactive agent should not be degraded in either of the dissolution sites but only released and absorbed once the system reaches the colon.1 Colon targeted drug delivery would additionally be valuable when a delay in absorption is desired from a therapeutically point of view in the treatment of diseases that have peak symptoms early in the morning, such as nocturnal asthma, angina or arthritis. The rapid advancement of biotechnology and genetic engineering resulted into availability of peptides and proteins at reasonable costs; there has been an increased interest in utilizing the colon as site for drug absorption. The potential candidates in this respect include analgesic peptides, oral vaccines, contraceptive peptides, growth hormone, insulin, erythropoietin, interferon, and interleukins (Saffran et al., 1988; Mackay and Tomlinson, 1993).2 The colon is a suitable absorption site for peptides and protein drugs due to: i) less diversity and intensity of digestive enzymes ii) less proteolytic activity of colon mucosa resulting in better prevention from hydrolysis and enzymatic degradation in duodenum and jejunum iii) increased systemic bioavailability iv) long colon residence time (5 days) and high responsiveness to absorption enhancers. There are number of methods or techniques through which colon drug targeting can be achieved, such as formation of prodrug, coating with pH sensitive polymers, coating with biodegradable polymers, designing formulations using polysaccharides, timed release system, pressure-controlled drug delivery systems, osmotic pressure controlled systems etc. Need of colon targeted drug delivery Colon targeted drug delivery system would asssure direct treatment at the disease site, lower dosing and fewer systemic side effects. Site-specific drug delivery system would allow oral administration of protein and peptide drugs, colon-specific formulation could also be used to prolong the drug delivery. Colon-specific drug delivery system is useful in the treatment of colon diseases. The colon is a site where both local or systemic drug delivery could be achieved. Topical treatment of inflammatory bowel disease, e.g. ulcerative colitis or Crohn’s disease. These inflammatory conditions are majorly treated with glucocorticoids and sulphasalazine (targeted). A number of others serious disorders of the colon, e.g. colorectal cancer, may also be capable of being treated more effectively if drugs were targeted to the colon. Formulations for colonic delivery are also suitable for delivery of drugs which are polar and/or susceptible to chemical and enzymatic degradation in the upper GI tract, highly affected by hepatic first pass metabolism, in particular, therapeutic proteins and peptides.3 Limitations and challenges in colon targeted drug delivery system A challenge in the development of colon specific drug delivery systems is to set up an appropriate dissolution testing method for in-vitro evaluation of the designed system. This is due to the rationale after a colon specific drug delivery system is quite different. As a site for drug delivery, the colon provides a near neutral pH, low digestive enzymatic activity, a long transit time and enhanced sensitivity to absorption enhancers; however, the targeting of drugs to the colon is very complicated. Owing to its location in the distal part of the alimentary canal, the colon is predominantly difficult to access. In addition to that the variation in pH values and different enzymes present throughout the gastrointestinal tract, through which the dosage form has to pass before reaching the target site, further complicate the consistency and delivery efficiency. Successful delivery through this site also needs the drug to be in solution form before it reaches the colon or alternatively, it should dissolve in the luminal fluids of the colon, but this can be a limiting factor for poorly soluble drugs as the fluid content in the colon is much lower and it is more viscous than in the upper part of the GI tract. The stability of the drug is also taken into consideration while designing a drug delivery system, because it may bind nonspecific way to dietary residues, intestinal secretions, mucus or faecal matter. Low surface area and relative tightness of the tight junctions in the colon can also limit drug transport across the mucosa and into the systemic circulation.4 Anatomy and physiology of colon The gastrointestinal tract is hollow muscular tube. It takes in nutrients and eliminate waste by such physiological processes as secretion, motility, digestion, absorption and excretion. Depending on structure and functions, the gastrointestinal tract is divided into the mouth, pharynx, oesophagus, stomach, small intestine and large intestine. The large intestine is approximately 1.5m in length and extends from the ileocaecal junctions to the anus. It is divided into four parts: caecum, colon, rectum and anal canal.5 The entire colon is approximately 5 feet (150 cm) long, and is divided into five major portions. Peritoneal folds called as mesentery which is supported by ascending and descending colon. The right colon consists of the caecum, ascending colon, hepatic flexure and the right half of the transverse colon. The left colon consists of the left half of the transverse colon, descending colon, splenic flexure and sigmoid. The rectum is the last anatomic segment before the anus. The human colon were shown in Figure1.The main functions of the colon is to make suitable environment for the growth of colonic microorganisms, storage reservoir of faecal contents, expulsion of the contents of the colon at an appropriate time and absorption of potassium and water from the lumen. The absorptive capacity is very high, at about 2000ml of fluid enters the colon through the ileocecal valve from which more than 90% of the fluid is absorbed6. The colon is involved in fermentation of polysaccharides and proteins, absorption of water and electrolytes and the formation, storage and elimination of faecal material. As a consequence of the functions of the colon, the colonic environment is generally viscous in nature. This could impact on the performance of drugs and delivery systems in this region of gut. Rapid water absorption in the ascending colon results in the distal colonic contents being more viscous. It has been estimated that the human colon contains only 220g of wet contents. In addition colon has a near neutral pH and is home to a viable microflora. These bacteria are involved in the fermentation of polysaccharides and proteins that have escaped digestion in the upper gut. Moreever the resident bacteria can also metabolize drug. The protein based drugs, insulin and calcitonin are rapidly degraded in simulated colonic contents5. Fig 1: Anatomy of colon Factors influencing colonic drug delivery: Physiological factors: 1. Transit through gastro intestinal tract Orally taken dosage forms first enters into stomach and small intestine via mouth and then reach colon. The nature and pH of the stomach affects the drug release and absorption. In order to effectively deliver tablet to colon in an intact form, the drug delivery systems should bypass the barriers in the stomach and small intestine. Gastrointestinal transit varies from 1 hr to 3 hrs depending upon the condition fasting or non-fasting respectively. In general, the small intestinal transit is not influenced by the physical state, size of the dosage form. The mean transit time of the dosage form is about 3-4 hours in order to reach the ileocecal junction and the time period is inconsistent. During this time the dosage form is exposed to enzymes present in small intestine. Compared to the other region of GIT, movement of material through the colon is slow. Total time for transit tends to be highly variable and influenced by number of factors such as diet particularly dietary fibre content , mobility, stress, disease condition and drugs. The colonic transit time is ranging from 20 to 30 hours, can be increase in presence of active disease 50 to 70 hours. Longer residence time with subsequent longer transit time and the contact of dosage form with micro flora in colon govern the release and improve absorption of drug from dosage form.7 Table 1: Transit time of dosage forms in GIT Organ Transit time(hr) Stomach >3 (fed) Small intestine 3-4 Large intestine 20-30 2. pKa of the drug, lipophilicity and gastrointestinal pH: The pH partition theory explains the process of drug absorption from the GIT and its distribution across all biological membranes. It states that for drug molecules of molecular weight greater than 100, which are mainly transported across the biological membranes by passive diffusion, the process of absorption is governed by: 1) The dissociation constant (pKa) of the drug. 2) The lipophilicity of unionized drug. 3) The pH at the absorption site. Since most of the drugs are weak electrolytes (weak acids or weak bases), their degree of ionization depends upon the pH of the biological fluid. If the pH on the either side of the membrane is different, then the compartment in which pH favors greater ionization of the drug will contain greater amount of drug, and only the unionized form of drug, if adequately lipid soluble, allowed to permeate the membrane passively until the concentration of unionized drug on both side of the membrane becomes equal i.e. until equilibrium is attained. The above statement of the hypothesis was on the basis of the assumptions that: 1) The GIT is a simple lipoidal barrier to the transport of drug. 2) Larger the fraction of unionized drug, faster the absorption(D. M. Brahmankar et al 2009). 3.pH of colon The pH of GIT varies in each individual. The food intakes, diseased state, etc.influences the pH of the GIT. This change in the pH in different regions of GIT is the basis for the development of colon targeted drug delivery systems. Coating with different polymers is done to target the drug to the site. Table 2: pH in different regions of gastrointestinal tract Part of GIT Ph Stomach (before meal) 1-2 Stomach (during digestion) 4 Smll intestine 6-7 Duodenum 6.6+0.5 Ileum 7.5+0.4 Caecum 6.4+0.4 Colon 5.5-7 Rectum 7 4. Colonic microflora A number of anaerobic and aerobic bacteria are present throghout entire length of the human GI tract. Over 400 different bacterial species have been found, 20-30% of which are of the genus bacteroids. The upper region of the GIT has a very small number of bacteria and predominantly consists of gram positive bacteria. The rate of microbial growth is greatest in the proximal areas because of high concentration of energy source. Concentration of microflora is generally about1011-1022 CFU/ml. It consists of Bacteroids, Bifidobacterium, Ruminococcus, Eubacterium and Clostridium. Chief metabolic reactions carried by the enzymes released from colonic microflora are hydrolysis and reduction. Table 3: Different microflora, enzymes and their actions Enzyme Microorganism Metabolic reactions catalysed Nitroreductase E. coli, Bacteroids Reduced aromatic and heterocyclic nitro compounds Azoreductase Clostridia, Lactobacilli, E.coli Reduced cleavage of azo compounds N oxide reductase, Sulphoxide reductase E. coli Reduced N oxides and sulphoxides Hydrogenase Clostridia, Lactobacilli Reduced carbonyl groups and aliphatic double bonds Esterases and amidases E. coli,P. vulgaris, B.subtilis, B. mycoides Cleavage of esters or amidases of carboxylic acid Glucosidase Clostridia, Eubacteria Cleavage of b- glycosidase of alcohols and phenols Glucoronidase E.coli, A. aerogenes Cleavage of b glycosidase of alcohols and phenols Sulphatase Eubacteria, streptococci Cleavage of O-sulfates and sulfamates Phamaceutical factors a) Drug candidate Drugs which show poor absorption in the stomach and intestine are most suitable for colon delivery. Drugs such as theophylline, nifedipine, diclofenac, ibuprofen, metoprolol, isoosorbide dinitrate, oxyprenolol and low molecular weight peptides and Peptide like drugs have been shown to be effectively absorbed from the colon. b) Drug carrier The selection of carrier for a particular drug candidate depends on the physicochemical nature of the drug as well as the disease for which the system is to be utilized. The factors such as chemical nature, stability and partition coefficient of drug and the type of absorption enhancers influences the carrier selection.9 Table 3: Drugs in colon targeted drug delivery Sr. No. Criteria Pharmacological class Drug and active agents 1 Drug used for local effect in colon Anti-inflammatory Drugs Oxyprenolol, Metoprolol, Nifedipine, Diclofenac, Sodium, Amylin, Antisense Oligonucleotide, 2 Drugs poorly absorbed from upper GIT Antihypertensive and antianginal drugs Ibuprofen, Isosorbides, Theophylline, Desmopressin Cyclosporine A, 3 Drugs for colon cancer Antineoplastics Pseudoephedrine, epoetin, Glucagon 4 Drugs that degrade in stomach and small intestine Peptides and proteins Bromopheniramine, 5 Flurouracil, Doxorubicin, Gonadoreline, Insulin, Interferones 5 Drugs that undergo extensive first pass metabolism Nitroglycerin and corticosteroids Nimustine, Bleomycin, Nicotine, Dexamethasone, protirelin, Sermorelin, Molgramoatim, Salotonin.