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Oral drug delivery has been known for decades as the most widely used route of administration among all the routes. Pharmaceutical product designed for oral delivery which are currently available in the market mostly immediate-release or conventional release, which maintains the drug concentration within the therapeutically effective range only, when administered several times a day. This results in a significant fluctuation of drug level in plasma.
An ideal dosage regimen in the drug therapy of any disease is the one which immediately attains the desired therapeutic concentration of drug in plasma (or at site of action) and maintains it constant for the entire duration of treatment. This is possible through administration of conventional dosage form in a particular dose and at particular frequency. The frequency of administration or dosing interval of any drug depends upon its half-life or mean residence time (MRT) and its therapeutic index. In most cases, dosing interval is shorter than the half-life of the drug resulting in a number of limitations associated with such a conventional dosage form.
1.2. ORAL CONTROLLED DRUG DELIVERY SYSTEM (Brahma N.S. and Kwon H.K., 2000; Khar R.K. and Vyas S.P., 2002; Pradeep K, et al., 2010)
The design of an oral controlled drug delivery system (CDDS) should be primarily aimed at achieving more predictable and increased bioavailability of drugs. Various approaches have been made to prolong the retention time of dosage form in the stomach. Retention of drug delivery system with prolonged overall gastrointestinal transit time and slow but complete release in the stomach improves bioavailability of drugs that have site specific absorption from stomach.
Thus, control of placement of a DDS in a specific region of the gastrointestinal tract (GIT) offer numerous advantages, especially for drugs exhibiting an absorption window in the GI tract or drugs a stability problem. Overall, the intimate contact of the DDS with the absorbing membrane has the potential to maximize drug absorption and may also influence the rate of drug absorption. These considerations have been tried to increase residence time and prolong drug release. One such method is the preparation of a device that remains buoyant in the stomach contents due to its lower density than that of the gastric fluids.
The gastro-retentive formulation can be retained in the stomach to aid in improving oral prolonged delivery of the drugs that have an absorption window in particular area of gastrointestinal tract. Hence, such system helps in continuously releasing the drug while reaching the absorption window, ensuring maximum bioavailability. These considerations have led to the development of oral controlled release (CR) dosage forms possessing retention capabilities. There are different approaches such as bio-adhesive system, swelling and expanding system, floating system and delayed gastric emptying system have continuously releasing the drug while reaching the absorption window ensuring maximum bioavailability.
Gastric retentive delivery systems potentially allow increased penetration of the mucus layer and therefore may increase drug concentration at the site of action.
ANATOMY AND PHYSIOLOGY OF STOMACH (Tortora G. and Derrickson B., 2003; Ramesh R.P. and Mahesh C.P.,2009; Aulton M.E., 2002)
Stomach is an organ with capacity for storage and mixing. It is located just below the diaphragm in the epigastric and left hydrochondriac region of the abdomen.
The stomach is anatomically divided into three parts:
Pylorus (Or antrum)
Figure 1.1: Structure of stomach
Stomach made up of fundus and body regions. They are capable of displaying a large expansion to accommodate food without much increase in intragastric pressure.
Stomach lining is devoid of villi and it consists of considerable number of gastric pits that contribute to storage capacity of the stomach. There are two main secretions: mucus and acid, produced by specialized cell in stomach lining. Mucus is secreted by goblet cells and gastric acid by parietal cells (oxyntric) The Mucus spread and cover the rest of GI tract.
The physiology and disease state of stomach has a direct effect on design of controlled drug delivery system because drug is absorbed from and enters into site of action. Factors such as pH, nature and volume of gastric secretions and gastric mucosa play an important role in drug release and absorption.
Table 1.1: Anatomical difference between different regions of the GIT
Transit time (hrs)
Environmental pH affects the performance of orally administered drugs. The pH of stomach in fasted condition is about 1.5 to 2 and in fed conditions it is usually 2 to 6. A large volume of water administered with oral dosage form changes the pH of stomach to pH of water initially. This change occurs because stomach does not have enough time to produce sufficient quantity of acid before emptying of liquid from the stomach.
The resting volume of stomach is about 25-52 ml. Gastric volume is important for dissolution of the dosage forms in-vivo. Meyer et al. conducted an experiment to study the effect of gastric fluid volume on absorption of controlled release theophylline dosage form in human beings. During this experiment they measured the gastric fluid volume of each subject. They estimated the mean gastric fluid volume in normal and achlorhydric subjects. The mean volume recovered by gastric aspiration over three consecutive, 15 min. time periods was 61+ 51 ml in achlorhydric subjects and 98+38 ml in normal subjects. Thus, there is such a large volume difference in gastric secretions that would significantly affect in-vivo dissolution of drugs.
Simple columnar epithelial cells line the entire mucosal surface of the stomach. Mucus, parietal and peptic cells are present in the body of stomach. These cells are associated with different functions. The parietal cells secrete acid whereas the peptic cells secrete precursor for pepsin. The surface mucosal cells secrete the mucus and bicarbonate. They protect the stomach from digestion by pepsin and from the adverse effects of hydrochloric acid. As mucus has lubricating effect, it allows chyme to move freely through the digestive system.
Acids, pepsin, gastrin, mucus and some other enzymes are the secretions of the stomach. Other potent stimulators of gastric acid are the hormones like gastrin, peptides, amino acids and gastric distention.
Liquid In fasted and fed conditions:
Volumes of liquids affect gastric emptying of liquids, larger the volume, faster the emptying. Gastric emptying of small volumes like 100 ml or less is governed by the MMC cycle whereas large volumes of liquids 200 ml or more are emptied out immediately after administration.
Effect of food on gastric secretion:
Type of meal and its caloric content, volume, viscosity and co-administered drugs affect gastric secretions and gastric emptying time. The rate of emptying primarily depends on caloric contents of the ingested meal. It does not differ for proteins, fats and carbohydrates as long as their caloric contents are the same.
The passage from stomach to the small intestine, called as gastric emptying. Delayed gastric emptying is recommended in particular where:
The drug dissolves slowly e.g. griseofulvin.
The food promotes drug dissolution and absorption e.g. griseofulvin.
Gastric emptying process occurs in both fasting and fed states; however, the pattern of motility differs like in the fasted state, it is characterized by an interdigestive series of electrical events in a cycle manner.
Phase I (Basal phase)
Period of no contraction lasting from 40 to 60 minutes.
Phase II (Preburst phase)
Period in termittent contraction and of similar
duration for 60 minutes.
Phase III (Burst phase)
Period of regular contraction at the maximal frequency lasting from 4 to 6 minutes.
Period of transition between Phase III and Phase I and lasts from 0 to 5 minutes.
Figure 1.2: Motility patterns of the GIT in the fasted state
Phase III has a housekeeping role and serves to clear all indigestible materials from the stomach and the small intestine. A complete cycle of these four phases has an average duration of 90 to 120 minutes.
Particle size and feeding state strongly affect the residence time of particles in stomach. Some other factors affecting gastric emptying are as follows: type of meal and its caloric content, volume, viscosity and co administered drugs. The rate of gastric emptying primarily depends on the caloric contents of the ingested meal. It does not differ for proteins, fats and carbohydrates as long as their caloric content is the same.
Solid in fasted and fed conditions:
Tablets or capsules do not have any significant calorific value. Therefore, the stomach treats them as an indigestible material. It is known that particle smaller than 2 mm in size are emptied from the stomach quickly. The density of the solid dosage form also affects the gastric emptying time. The average time required for a dosage unit to traverse the GIT is 3-4 hours, although slight variations exist among various dosage forms.
GASTRO-RETENTIVE DOSAGE FORM
(Jain N.K., 2004; Garg R. and Gupta G.D., 2008)
GRDFs offers several advantages over immediate release dosage form, including the minimization of fluctuations in drug concentration in plasma and at the site of action over prolonged periods of time, resulting in optimized therapeutic efficiencies and reduce the side effect, reduction of total dose administered and reduction of administration frequency, leading to improved patient compliances. An absorption window exists because of physiological, physicochemical, or biochemical factors. Drugs having site-specific absorption are difficult to design as oral CRDDS because only the drug released in the region preceding and in close vicinity to the absorption window is available for absorption. After crossing the absorption window, the released drug goes waste with negligible or no absorption (Fig 1.3a). This phenomenon considerably decreases the time available for drug absorption after its release and expose the success of the delivery system. The GRDDS can improve the controlled delivery of the drugs which exhibit an absorption window by continuously releasing the drug for a prolonged period before it reaches its absorption site, thus ensuring its optimal bioavailability (BA) (Fig 1.3b).
Figure 1.3: Comparison of (a) conventional and (b) gastroretentive drug delivery system
FACTORS AFFECTING GASTRIC RETENTION
(Anilkumar J.S. and Harinath M.N., 2008; Shweta A. et al., 2005)
There are several factors that can affect gastric retention of an oral dosage form. These factors are as follows.
Shape of dosage form
Single or multiple unit formulation
Fed or unfed state
Nature of meal
Frequency of feed
VARIOUS GASTRO-RETENTIVE DRUG DELIVERY SYSTEM
(Sable V. et al., 2010; Mayavanshi A.V. and Gajjar S.S., 2008)
Various approaches have been pursued to increase the retention of an oral dosage form in the stomach. These include:
Bio adhesive delivery system
Size increasing system/ Expandable system
High density system
Floating drug delivery system / Low density system
A. Bioadhesive system: Bio adhesive system is adhering to mucosal surface of the stomach after the oral. This have high turnover rate of gastric mucus and resulting limited retention time. The disadvantage of this system is possibility of oesophageal binding.
B. Sized increasing drug delivery system or swelling system: This dosage forms have initially small size and when enter in the stomach significantly increasing its size above the diameter of the pylorus. The expanded state should be achieved rapidly in order to prevent premature emptying through the pylorus. Conversely, the system should also guarantee their clearance from the stomach after predetermined time intervals to avoid accumulation upon multiple administrations.
Figure 1.4: Approaches of gastro retentive drug delivery system
C. High-density system: This system is coated the drug with inert material. These coated pellets which have density greater than that of stomach content (1.004 gm/cm3). This system having density of ~ 3 gm/cm3 is retained in the range of the stomach.
D. Floating drug delivery system:
Floating drug delivery system (FDDS) or hydro dynamically balanced system has a bulk density lower than gastric fluid. After release of drug, the residual system is empty from the stomach. This may lead to increase the GRT and better control of drug concentration.
Figure 1.5: Various approaches of gastro retentive drug delivery system
TECHNOLOGICAL DEVELOPMENT IN FDDS
(Bandyopadhyay A.K., 2008; Patil J.M., et al., 2006)
Based on the mechanism of buoyancy, two distinctly different types, i.e. non-effervescent and effervescent systems have been utilized in the development of FDDS.
A. Effervescent FDDS:
Effervescent system is prepared with swellable polymer such as methocel or effervescent components like sodium bicarbonate or citric acid or tartaric acid.
a. Multiple-unit oral floating drug delivery system:
Recently a multiple-unit type of floating pill, which generates carbon dioxide gas, has been developed. The system consisted of sustained-release pills as seeds surrounded by double layers. The inner layer an effervescent layer containing both sodium bicarbonate and tartaric acid. The outer layer was a swellable membrane layer containing mainly polyvinyl acetate and purified shellac. Moreover, the effervescent layer was divided into two sub layers the sodium bicarbonate was contained in the inner sub layer and tartaric acid was in the outer layer.
Figure 1.6: Multiple unit oral floating drug delivery system
When the swollen pills are formed, like balloons, they have a density much lower than 1.004 gm/cm3. The reaction was due to carbon dioxide generated by neutralization in the inner effervescent layer with the diffusion of water through the outer swellable membrane layer.
A floating system utilizing ion-exchange resins has been developed. The system consisted of resin beads, which were loaded with bicarbonate and a negatively charged drug that was bound to the resin. The resultant beads were then encapsulated in a semi permeable membrane to overcome rapid loss of carbon dioxide. As result of this reaction, carbon dioxide was released and trapped in the membrane. In contrast, the uncoated beads sink quickly. Radioactivity measurement by scintigraphy showed that gastric residence was substantially prolonged, compared with a control, when the system was given after a light, mainly liquid meal.
Figure 1.7: Mechanism of effervescent drug delivery system
Furthermore, the system was capable of slow release of drug, a Property which widens the scope of such floating system for SR preparation of drugs possessing negative charge since they can be easily bound to the resin in combination with bicarbonate ions. Two patents on FDDS issued to the Alza Corporation disclosed drug delivery devices for the controlled and continuous administration of medicinal agents. Following figure shows mechanism of floating of effervescent drug delivery system.
b. Inflatable gastrointestinal drug delivery system: The residence time of the drug delivery device in the stomach can also be sustained by incorporation of an inflatable chamber, which contains a liquid, e.g., ether that gasifies at body temperature to cause the chamber to float in the stomach.
Figure 1.8: Inflatable gastrointestinal drug delivery device
c. Intragasric osmotically controlled drug delivery system: It is comprised of an osmotic pressure controlled drug delivery and an inflatable floating support in a bio-erodible capsule. When the drug delivery device reaches the site of drug administration e.g. the stomach, the capsule quickly disintegrates to release the intragastric osmotically controlled drug delivery device. The inflatable floating support is made from a deformable hollow polymeric bag that contains a liquid that gasifies at body temperature to inflate the bag.
Figure 1.9: Intragasric osmotically controlled drug delivery device.
B. NON-EFFERVESCENT FDDS
Floating microsphere are gastro-retentive delivery systems based on non-effervescent approach.
a. Hydro dynamically balanced intragastric delivery system
The hydro dynamically balanced gastrointestinal drug delivery systems, in either capsule or tablet form, is designed to prolong GI residence time in an area of the GI tract to maximize drug reaching its absorption site in solution state and hence, ready for absorption. It is prepared by incorporating a high level (20-75% w/w) of one or more gel-forming hydrocolloids e.g. hydroxyl ethylcellulose, hydroxypropyl cellulose, hydroxyl propyl methyl cellulose and sodium carboxy methyl cellulose into the formulation and then compressing these granules into a tablets.
On contact with gastric fluid the hydrocolloid in this intragatric floating device start to become hydrated and forms a colloid gel barrier around its surface with thickness growing with time. This barrier controls the rate of solvent penetration into the device and the rate of drug release from the device (Fig. 1.10).
Figure 1.10: Working principle of hydrodynamically balance system
b. Bilayer tablet: A bilayer tablet can be prepared to contain one immediate-release layer and one sustained-release layer. After the initial dose is delivered by the immediate release layer, the sustained layer absorbs the gastric fluid and forms a colloidal gel barrier on its surface.
Figure 1.11: Intragastric floating bilayer tablet
c. Intragastric floating gastrointestinal drug delivery system:
A gastrointestinal drug delivery system can be made to float in the stomach by incorporating a floatation chamber, which may be a vacuum or filled with a harmless gas.
Figure 1.12: Intra-gastric floating drug delivery device
1.8. RECENT ADVANCES (Shah S.H. et al., 2009)
1.8.1. Floating multi-layer coated tablets:
multi-layer coated tablets were designed based on gas formation. The
consists of a
-containing core tablet coated with a protective layer (hydroxypropyl methylcellulose), a gas forming layer (sodium bicarbonate) and a gas-entrapped membrane respectively. The acrylic polymers Eudragit and ethyl cellulose were suitable film for the system, and was chosen as gas-entrapped membrane due to its high flexibility and high water permeability.
1.8.2. Raft System
A gel-forming solution (e.g. sodium alginate solution containing carbonates or bicarbonates) swells and forms a viscous cohesive gel containing entrapped CO2 bubbles on contact with gastric fluid. Formulations also typically contain antacids such as aluminum hydroxide or calcium carbonate to reduce gastric acidity.
1.8.3. Magnetic system
This system is based on a simple idea that the dosage form contains a small internal magnet and a magnet placed on the abdomen over the position of stomach. The internal tablet guided by the oesophagus with an external magnet. These systems seem to work, the external magnet must be positioned with a degree of precision that might compromise patient compliance.
1.9. POLYMERS AND OTHER INGREDIENTS
(Shah S.H. et al., 2009; Bhushan B.L. et al., 2006)
Following types of ingredients can be incorporated into HBS dosage form in addition to the drugs:
Hydrocolloids (20%-75%): They can be synthetics, anionic or non-ionic like hydrophilic gums, modified cellulose derivatives. Eg. Chitosan, agar, HPMC(K4M, K100M and K15M), Gellan gum, Sodium CMC, MC, HPC
Inert fatty materials(5%-75%): Edible, inert fatty materials having a specific gravity of less than one can be used to decrease the hydrophilic property of formulation and hence increase buoyancy. Eg. Beeswax, fatty acids, long chain fatty alcohols, Gelucires® 39/01.
Effervescent agents: Sodium bicarbonate, citric acid, tartaric acid, Di-SGC (Di-Sodium Glycine Carbonate, CG (Citroglycine).
Release rate accelerants(5%-60%): eg lactose, mannitol
Release rate retardants (5%-60%): eg Dicalcium phosphate, talc.
Buoyancy increasing agents (upto80%): eg. Ethyl cellulose
Low density material: Polypropylene foam powder (Accurel MP 1000®).
1.10. SUITABLE DRUG CANDIDATES FOR GASTRO-RETENTION
(Garg R. and Gupta G.D., 2008; Anilkumar J.S, Harinath M.N.2008)
Narrow absorption window in GI tract, e.g., Levodopa.
Primarily absorbed from stomach and upper part of GI tract, e.g., chlordiazepoxide and cinnarazine.
Drugs that degrade in the colon, e.g., ranitidine hydrochloride
Drugs required exerting local therapeutic action in the stomach e.g. Misoprostol, 5-Flurouracil, antacids and antireflux preparations, anti Helicobacter pylori agents.
Drugs unstable in lower part of GI tract: e.g. Captopril.
Drugs insoluble in intestinal fluids (acid soluble basic drugs): e.g. Chlordiazepoxide, Chlorpheniramine, Cinnarizine, Dizapam, Diltiazem, Metoprolol, Propranolol, Verapamil.
LIMITATIONS OF FDDS
(Mayavanshi A.V. and Gajjar S.S., 2008; Anilkumar J.S. and Harinath M.N., 2008)
The major limitation of floating system is requirement of a sufficient high level of fluids in the stomach for the drug delivery to float.
Floating system is not applicable for drugs have solubility and stability in gastric fluids.
Drugs which are irritant to gastric mucosa cannot be applicable to GRDFs, floating system.
The residence time in the stomach depends upon the digestive state. Hence FDDS should be administered after the meal.
The ability of drug to remain in the stomach depends upon the subject being positioned upright.
The dosage form should be administered with a minimum of glass full of water (250 ml).
ADVANTAGES OF FDDS
(Garg R. and Gupta G.D., 2008; Mayavanshi A.V, Gajjar S.S.2008)
Drugs that are absorbed through the stomach, e.g. Riboflavine.
Drugs that for local action in the stomach, e.g. antacids.
It reduces fluctuations in circulating blood level of drug as shown by the conventional dosage form.
It shows more uniform levels of drug in plasma.
It releases drug slowly and for prolonged period of time and hence reduces dosing frequency.
It increases patient compliance as the dosing frequency is reduced.
Site specific drug delivery.
Retention of the drug in the GRDF at the stomach minimizes the amount of drug that reaches the colon, hence minimizes adverse activity at the colon.
APPLICATIONS OF FLOATING DRUG DELIVERY SYSTEMS (Bandyopadhyay A.K., 2008; Mayavanshi A.V, Gajjar S.S.,2008)
Sustained Drug Delivery
It prolongs the drug release. The disadvantage of controlled release formulations are it release the drug fastly compared to sustained formulations.
Site-Specific Drug Delivery
These systems are particularly used for stomach or the proximal part of the small intestine, eg, furosemide.
Drugs have poor bioavailability because of site specific absorption from the upper part of the gastrointestinal tract.
Table 1.2: Examples of various formulations of FDDS
Aspirin, Grisiofulvin, p-nitroanilline, Ibuprofen, Terfinadine,
Diclofenac sodium, Indomethacin, Prednisolone
Several basic drugs
Chordiazepoxide HCL, Diazepam, Furosemide,
L-Dopa, Benserazide, Misoprostol, Propranolol HCL.
Acetoaminophene, Acetylsalicylic acid, Amoxicillin trihydrate, Ampicillin, Atenolol, Chlorpheniramine, Cinnarizine, Diltiazem, Flurouracil, Isosorbide mononitrate, Isosorbide dinitrate, Quinidine gluconate.
Microspheres are solid, approximately spherical particles ranging 1-1000µm in size. They are made up of polymeric substances in which the drug is dispersed throughout the microsphere matrix. The substances used in the formulation are biodegradable synthetic polymers and natural products such as starches, gums, proteins, facts and waxes. The natural polymers of choice are albumin and gelatin, the synthetic ones being polylactic acid and polyglycolic acid. The polymers used to manufacture microspheres are chosen according to their solubility, stability profile, and process safety.
Administration parameters that can be satisfactorily controlled
Taste and odour masking
Conversion of oil and other liquids, facilitating ease of handling
Protection of the drugs from the environment
Delay of volatilization
Freedom from incompatibilities between drugs and excipients, especially the buffers
Improvement of flow properties
Safe handling of toxic substances
Dispersion of water insoluble substances in aqueous media
Production of sustained release, controlled release and targeted medications
Advantages of Microspheres
They facilities accurate delivery of small quantities of potent drugs and reduced concentration of the drugs at sites other than the target organ or tissue
They provide protection for unstable drugs before and after administration, prior to their availability at the site of action
They enable controlled release of drugs
Examples of drugs that are formulated as microspheres include Antineoplastic drugs, Narcotic antagonists, Steroid hormones, Leutinising hormone analogs, Antibiotics and other macromolecules.
Preparation of Microspheres
Wax coating and hot melt
Spray coating and pan coating
Formation of water-in-oil emulsions
Wax coating and Hot melt
An aqueous drug solution is dispersed in molten wax to form a water-in-oil emulsion, which is then emulsified in a heated external aqueous phase to form a water-in-oil-water emulsion. The system is cooled and the microcapsules collected. For highly aqueous soluble drugs, a non-aqueous phase can be used to prevent loss of drug to the external phase. Wax-coated microcapsules are inexpensive and often used and they release the drug more rapidly than polymeric microcapsules. Carnauba wax and beeswax can be used as coating materials and mixed to achieve the desired characteristics.
Spray Coating and Pan Coating
Spray coating and pan coating employer heat-jacketed coating pans in which the solid drug core particles are rotated and the coating material is sprayed. The core particles are in the size range of micrometers up to a few millimerers. The coating material is usually sprayed at an angle from the side into the pan. The process is continued until an even coating is achieved. Coating a large number of small particles may provide a safer and more consistent release pattern than coated tablets. In addition, several batches of microspheres can be prepared with different coating thicknesses and mixed to achieve specific controlled release patterns.
The coacervation technique is one in which solid particles are entrapped in coacervate system methods, tiny coacervate droplets are formed, which sediment or coalesce to form a separated coacervate phase. The coacervate forms around any core material that may be present, such as drug particles. Agitation of the coacervate system can prevent coalescence and sedimentation of the droplets, which can be cross-linked to form stable microcapsules by adding an agent such as glutaraldehyde or by applying heat. Cross-linking of the coacervate emulsion droplets and hence form microcapsules.
Spray drying is a single-step, closed-system process applicable to a variety of materials, including thermolabile materials. This process is often used commercially as a closed system; it is used commercially practice and the production of sterile materials. The drug and the polymer coating materials are dissolved in a suitable solvent (aqueous or non-aqueous) or the drug may be present as a suspension in the polymer drug solution. Alternatively, it may be dissolved or suspended within an emulsion or coacervate system. The size of microsphere is controlled by the rate of spraying, feed rate of the polymer drug solution, nozzle size, temperature in the drying and collecting chamber and the size of these chambers.
This is one of the earliest methods of microsphere manufacture. The polymer and the drug must be soluble in an organic solvent. The solution containing the polymer and the drug may be dispersed in an aqueous phase to form droplets. Continuous mixing and elevated temperatures may be employed to evaporate the more volatile organic solvent and leave the solid polymer-drug particles suspended in anaqueous medium. The particles are finally filtered from the suspension.
Precipitation is a variation of the evaporation method. Here, the emulsion consists of polar droplets dispersed in a nonpolar medium. The solvent may be removed from the droplets by suing a cosolvent. The resulting increase in polymer drug concentration causes precipitation, forming a suspension of microspheres.
Ulcer is caused due to an imbalance between the aggressive factors such as acid, pepsin and the intestinal bacteria Helicobacter pylori and the defensive factors such as gastric mucous and bicarbonate secretion, prostaglandins, nitric oxide and innate resistance of the mucosal cells. Ulcer occurs in the part of gastrointestinal tract which is exposed to gastric acid and pepsin.
But some ulcer is an open sore of the skin, eyes/mucous membrane, often caused, but not exclusively, by an initial aberration generally maintained by an inflammation; an infection and or other medical conditions which impede healing, or in other words, it is a macroscopic discontinuity of the normal epithelium (Microscopic erosion).
Figure 1.13: Ulcer perforation
Most common causes for ulcer are bacterial ulceration, viral infection, fungal infection, cancer-both primary and secondary, venous statis, arterial insufficiency, diabetes, rheumatoid arthritis, amyloidosis, hypertension.
MAJOR TYPES OF ULCER
Peptic ulcer can be classified as acute and chronic ulcer. Gastric and duodenal ulcers also defined as peptic ulcers. Helicobacter pylori thrives in an acidic medium and stress has been demonstrated to cause the production of excess stomach acid.
Figure 1.14: Peptic ulcer disease
Many factors are involved in the incidence and type of ulcer including metabolic, dietary, genetic, climate, life style and occupational interferences.
Some drugs seems to cause ulcers are aspirin, NSAIDS, alcohol, acids and bile salts. Also ischemia and Helicobacter pylori causes ulcer.
Present day medical management of ulcer involves oesophagogastroduodenoscopy (EGD), a form of endoscopy, antacids treatment or by means of surgical repair (vagotomy) of the perforations. Treatment may also be aimed at lowering the amount of acid by neutralizing the acid.