This document discusses distribution and excretion of chloramphenicol eye drops. It begins by providing background on the pharmacokinetics of drugs administered via eye drops, noting the challenges with low bioavailability due to eye anatomy and defenses. The document then focuses on chloramphenicol, describing how it works as a bacteriostatic antibiotic and the goals of observing its distribution and excretion when administered via eye drops.
This document discusses distribution and excretion of chloramphenicol eye drops. It begins by providing background on the pharmacokinetics of drugs administered via eye drops, noting the challenges with low bioavailability due to eye anatomy and defenses. The document then focuses on chloramphenicol, describing how it works as a bacteriostatic antibiotic and the goals of observing its distribution and excretion when administered via eye drops.
This document discusses distribution and excretion of chloramphenicol eye drops. It begins by providing background on the pharmacokinetics of drugs administered via eye drops, noting the challenges with low bioavailability due to eye anatomy and defenses. The document then focuses on chloramphenicol, describing how it works as a bacteriostatic antibiotic and the goals of observing its distribution and excretion when administered via eye drops.
In the process of drug pharmacokinetics after a drug undergoing phase
absorption, distribution, biotransformation, and the drug is finally experiencing a phase of excretion. Excretion is the displacement of the systemic circulation of drugs heading to the organs of excretion. Experienced drug excretion aims to detoxify drugs, because it is known that the drug is considered a poison/foreign substances by the body. Chloramphenicol works by inhibiting protein synthesis germs. The drug is bound to the Ribosome sub-unit 9s and inhibits the enzyme peptidil transferase so the peptide bonds are not formed in the process of protein synthesis germs. Chloramphenicol are bacteriostatic. At high concentrations of chloramphenicol sometimes are bakterisid against particular germs. This trial will be observed on distribution and excretion of chloramphenicol eye drops
1. INTRODUCTION required drug concentration in the place of absorption and sustaining it for Ophthalmic drug forms have appropriately long time, which in turn been one of the most important and contributes to smaller application widely developed areas of frequency(1). pharmaceutical technology for dozens of years. The main reason of One of the first modifications to continuingly strong interest of scientists conventional forms of ophthalmic drugs in these drug forms is the problem of a was introducing polymers to low bioavailability of medicinal formulation, which enabled longer substance after the application to the contact time of active ingredient and the eyeball. It is caused by, amongst other corneal surface, thus increasing its reasons, the complicated anatomical bioavailability. Next possibility to structure of the eye, small absorptive modify the ophthalmic forms active surface and low transparency of the ingredients’ bioavailability involved cornea, lipophilicity of corneal introducing excipients to formulation, epithelium, metabolism, enzymolysis, which enhanced drugs’ penetration into bonding of the drug with proteins the eyeball. These excipients included contained in tear fluid, and defence chelating agents, surfactants, and mechanisms, that is, tear formation, cyclodextrins, which, along with active blinking, and flow of the substance ingredients, form inclusion complexes. through nasolacrimal duct (1). This increases solubility, permeability, and bioavailability of poorly soluble Low capacity of conjunctival sac, drugs (1). that is, approximately 30 L without blinking [4], and the aforementioned The newer drug forms, on which defence mechanisms cause decrease in in recent years research has been drug concentration in the place of conducted in order to achieve a application and shorten the time during controlled release of drug to eyeball which the active ingredient stays in the tissues, include multicompartment place of absorption. The primary carrier systems, inserts, collagen purpose for the development of shields, contact lenses, and the so-called ophthalmic drug forms is to achieve the in situ gels [1–3, 5]. The advantages of using these new drug forms of Eye drops are usually used on the controlled release are, among others, eyes for the purpose of local effects on increasing bioavailability of substance treatment of the surface of the eye or on through extending the time of its contact the inside, where the most often used is with cornea—which can be achieved by a solution in water. Because of eye effective adhesion to the corneal capacity to withstand or keep the fluid surface, the possibility of targeted limited, in general eye medication is therapy preventing the loss of drug to given on a small volume. Larger volume other tissues, ensuring patient’s comfort of liquid preparation can be used to when applying the drug form and during refresh or wash eyes(4). the whole therapy, and increasing The normal volume of tears in resistance to eye defence mechanisms, the eye is 7micro liter. Where the eyes like tearing (2). are not blinking can contain at most Eye drops are accessible in the 30micro liter liquid, while the eyes are forms of water and oil solutions, blinking only can save 10 micro liter emulsions, or suspensions of one or fluids. Excess fluid, both from normal more active ingredients, which may production or added from the outside, contain preservatives if stored in quickly flowed into the eye. The size of multiuse packaging. These forms are each drop which is incorporated into a sterile and isotonic. The optimum pH 50-drug solution usually micro liter for eye drops equals that of tear fluid (based on 20 drops / ml), so the droplet and is about 7.4. In deciding whether to inserted will mostly be lost. Ideal buffer the drug in this form, one should volume of drug solution to be used, take into account the stability of active based on the capacity of the eye ie 5-10 ingredient and the tissue tolerance to the micro liter. Because the dose of preparation. If the pH value gets outside microliter from eye dropper is usually the range of 4–8 which is tolerated by absent or not used by the patient, the eye, the patient may feel discomfort, loss of that drug inserted a standard eye there may be irritation, and the drug dropper is common. If desired therapy bioavailability can decrease because of with a few drops, it is recommended to increased tearing (3). repeat every 5 minutes. This matter allows the buildup of drugs in the networks in the water. Examples of such corner, while losing through drainage polymers include polyvinyl alcohol, small. Sometimes the use of a solution poloxamers, hyaluronic acid, for the eyes with greater concentrations carbomers, and polysaccharides, that is, of the drug can be replaced for cellulose derivatives, gellan gum, and treatment with repeated droplets of the xanthan gum. The aforementioned solution more dilute(5) . carbomer is used in liquid and semisolid formulations as a suspending substance The buffer may be used in an eye or a substance which increases solution because of one or all of these viscosity, whereas hyaluronic acid is the following reasons to reduce the used as a polymer, forming discomfort of the patient to guarantee biodegradable and biocompatible stability of the drug, and to supervise matrix, which enables extending time the therapeutic activity of medicinal periods of drug release (6). substances. The research has proved that Tears have a normal pH of 7.4 maximum increase of penetration and have a buffer ability. The use of a through the cornea by a solution in the solution containing eye medication form of eye drops takes place when the stimulates the flow of tears trying to viscosity falls into the range of 15 to neutralize any excess hydrogen or 150 mPas. An example of “extreme” hydroxyl ions imposed on eyes together use of substances increasing viscosity is solution (5) forming gels, which would enable Extending the time period of reducing the frequency of drug contact with cornea and improving application to once daily. It has been bioavailability of substances may be proved that synthetic obtained by increasing formulation’s polyoxyethylene-polyoxypropylene viscosity. Substances which have such block copolymer (poloxamer 407) is effect include hydrophilic polymers of suitable for use as a carrier in high molecular weight which do not ophthalmic formulation with diffuse through biological membranes pilocarpine, which stimulates the active and which form three-dimensional ingredient. The main disadvantage of this formulation is blurring of vision, chloramphenicol degradation. This drug which negatively affects its is very unstable in an alkaline acceptability among patients (6). atmosphere, andhis reactions appear to be catalyzed by both acid and specific Chloramphenicol is one of the bases(7). Chloramphenicol degradation most chemically known antibiotics through dehalogenation is not a part of stable in all usage. Chloramphenicol has the role in the picture of total excellent stability at room temperature degradation, at least below pH 7(7). and pH range 2 to 7, its maximum stability is achieved at pH 6. At The degradation rate depends temperature 25°C and pH 6, has a linearly on the concentration of buffer, half-life of almost 3 years. The cause buffer species acting as common acids the main occurrence of chloramphenicol and common bases. The rate of degradation in aqueous media is the hydrolysis of chloramphenicol is not hydrolytic solutionon the amide circle. depending on ionic strength, and The reaction rate lasted under the first unaffected by the concentration of order and was not depending on the dihydrogen phosphate ions,thus its ionic strength of the media (7). catalysis activity is thought to be derived from the action of the Ongoing hydrolysis of monohydrogen ionphosphate as general chloramphenicol catalyzed common base catalysis(7). acids / common bases, but in the pH range of 2 to 7, the reaction rate is Chloramphenicol is a independent of pH. Species catalyzing broad-spectrum antibiotic that was is a common acid or a common base derived from the bacterium contained in a buffer solution used; Streptomyces venezuelae and is now particularly in monohydrogen phosphate produced synthetically. ions, undissociated acetic acid, and Chloramphenicol is effective against a monohydrogen acid and dihydrogen wide variety of microorganisms, but due citrate ions can catalyze the degradation to serious side-effects (e.g., damage to process. In under pH 2, hydrolysis of the bone marrow, including aplastic hydrogen ion-specific catalyzed plays a anemia) in humans, it is usually major role on occurrence of reserved for the treatment of serious and life-threatening infections (e.g., typhoid major route of elimination of fever). Chloramphenicol is chloramphenicol is hepatic metabolism bacteriostatic but may be bactericidal in to the inactive glucuronide. This high concentrations or when used metabolite, as well as chloramphenicol against highly susceptible organisms. itself, is excreted in the urine by Chloramphenicol stops bacterial growth filtration and secretion. Over a 24 hour by binding to the bacterial ribosome period, 75% to 90% of an orally (blocking peptidyl transferase and administered dose is so excreted; about inhibiting protein synthesis (8). 5% to 10% is in the biologically active form(8). Chloramphenicol is a semisynthetic,broad-spectrum antibiotic Chloramphenicol inhibits protein derived from Streptomyces venequelae synthesis in bacteria and, to a lesser with primarily bacteriostatic activity. extent, in eukaryotic cells. The drug Chloramphenicol diffuses through the readily penetrates into bacterial cells, bacterial cell wall and reversibly binds probably by a process of facilitated to the bacterial 50S ribosomal subunit. diffusion. Chloramphenicol acts The binding interferes with peptidyl primarily by binding reversibly to the transferase activity, thereby prevents 50 S ribosomal subunit (near the site of transfer of amino acids to the growing action of the macrolide antibiotics and peptide chains and blocks peptide bond clindamycin, which it inhibits formation. As a result bacterial protein competitively). Although binding of synthesis is blocked and impede tRNA at the codon recognition site on bacterial cell proliferation (8). the 30 S ribosomal subunit is thus undisturbed, the drug appears to prevent Rapidly and completely the binding of the amino absorbed from gastrointestinal tract acid-containing end of the aminoacyl following oral administration tRNA to the acceptor site on the 50 S (bioavailability 80%). Well absorbed ribosomal subunit. The interaction following intramuscular administration between peptidyl transferase and its (bioavailability 70%). Intraocular and amino acid substrate cannot occur, and some systemic absorption also occurs peptide bond formation is inhibited. after topical application to the eye. The Chloramphenicol can also inhibit 2.3.1.Preparation mitochondrial protein synthesis in 1. The group chose 2 volunteers for mammalian cells, perhaps because the experiment. mitochondrial ribosomes resemble 2. Before an ophthalmic drug, the bacterial ribosomes (both are 70 S) bladder is emptied and urine more than they do the 80 S cytoplasmic taken for control, saliva is also ribosomes of mammalian cells. taken for control, as well as tears Mammalian erythropoietic cells seem to taken for control. be particularly sensitive to the drug(8). 3. Volunteers were given 2 drops of 2. RESEARCH METHODOLOGY chloramphenicol eye medicine. 4. Saliva and urine samples taken 2.1 Time and place every 15 minutes for 3 hours and
This experiment was conducted tears every 30 minutes for 3
at Pharmacology Laboratory, Faculty of hours. Do urine and saliva
Mathematics and Natural Sciences, analysis.
Sriwijaya University of Palembang. The
2.3.2.Analytical Procedures time of its implementation on 26 sept , 2017. 1. Dissolve saliva, tears and urine in 1ml ethanol 95%. 2. Add 3ml of water mixture and 1
2.2 Tools and Materials part KCL and 9 parts water.
3. Add 50 mg Zn powder. The tools used are dropper 4. Heat over the water bath for 10 drops, test tube, ointment pot, test tube.. minutes The ingredients used include 5. Pour the pour. chloramphenicol drops 5%, ethanol 95 6. Add 1o mg of anhydrous sodium %, KCL, aquadest, anhydrous sodium acetate and 2 drops of benzoyl acetate, Zn powder, benzoyl chloride, chloride. Shake for 10 minutes. FeCL3, HCL 0.1 N 7. Add 0.5 ml of fecl3 solution, if necessary add HCL dilute 2.3. Procedure enough to make clear solution and change the color of violet two hours at 48 hours early and four red to purple. hours afterwards. Sleep does not need to be disturbed for eye drops. The usual 3. RESULT AND DISCUSSION treatment takes five days. The experiment at this time Chloramphenicol is a bacteriostatic that made an observation of the distribution has a wide spectrum of gram-negative and excretion of chloramphenicol eye and gram-positive bacteria. drops through urine, saliva and tears. Chloramphenicol provides antibacterial With the aim of knowing effects by binding to bacterial pharmacokinetics of chloramphenicol ribosomes and inhibits bacterial protein eye drops. This experiment used two synthesis. In acute conjunctive disease, volunteers for an experimental usually caused by staphilokoci or administration of chloramphenicol eye streptococi in adults, and also drops previously emptied of each Haemophilus influenzae and Moraxella volunteer bladder aiming to see the catarrhalis. The characteristics of a excretion of the drug which was given conjunctive infection are (bacteria or not mixed with other compounds to be virus): the eyes look swollen and red or identified chloramphenicol compounds pink, uncomfortable eyes are felt with a by quantitative identification with the burning or sandy feeling (but not sharp compound the previously treated FeCl 3 or important pain) and dirt. Eye reagents with 95% ethanol. droppings are sticky and mokopurulent Chloramphenicol is one of the most to bacteria and more watery than viral chemically stable antibiotics in all infection. Bacterial conjunctivitis can applications. Chloramphenicol itself also make eyes difficult to open in the excellent stability at room temperature morning due to dry debris. Conjunctive range of 3-7 ph is a good stability. infections usually begin in one eye and then spread elsewhere. Vision is not Chloramphenicol is indicated for disturbed usually, but when associated topical treatment of acute bacterial with eye droppings, causing blurred conjunctive infections in adults, elderly, vision, and there are particles that look and children 2 years or older. Used as motionless. There is no photophobia. many as one drop in the infected eye for Drugs that enter the body will process of drug absorption is the undergo pharmacokinetics process. transfer of drugs from one place to Basically pharmacokinetics is all the another, from the gastrointestinal tract process that the body does to drugs in to the blood vessels, to the penetration the form of absorption, distribution, of the membrane. The main factors metabolism (biotransformation), and affecting absorption after oral excretion. Our body can be regarded as administration of the drug, there are 3 a large room, consisting of several factors, namely: physiological factors, compartments separated by cell physico-chemical factors, and membranes. While the process of formulation factors. The medicine in the absorption, distribution and excretion of dosage form will be released into drug drugs from within the body in essence particles in the body fluids to be take place with the same mechanism, dissolved and the drug is in the form of because this process depends on the a solution that can be degraded or trajectory of the drug through the absorbed into the liver and can be trajectory. The cell membrane consists excreted (if polar drugs, either directly of a layer of lipoprotein (fat and protein) excreted) or into the central containing many small pores, filled with compartment bound form or free form, water. Membranes can be penetrated achieving dynamic equilibrium) then easily by certain substances, and the drugs are distributed and only the difficult to pass through other over-the-counter drugs reach the substances, it is called semi permeable. peripheral tissues that cause Lipofil substances (like fat) that are pharmacological effects. The drug after easy to laryt in fat and without electric absorption will spread through the blood charge generally run more smoothly circulation throughout the body. In the than hydrophilic substances with charge circulation, most drugs are distributed (ion). through the membrane of the body in a way that is relatively easier and faster Drugs consumed by living than the elimination or expenditure of things will essentially undergo the drugs. Distribution is the process of a process of adsorption, distribution, drug that reversibly leaves the metabolism and elimination. The bloodstream and enters the interstitium (extracellular fluid) or to the tissue cells. Within 24 hours 75-90% of oral doses Drug deliveries from plasma to are excreted in the form of metabolites interstinum depend primarily on blood and 5-10% in the original form. While flow, capillary permeability, the degree on the sempel urine is known to have of ionic bonding of the drug to plasma chloramphenicol content of each time, it or tissue proteins and the is proved by positive results reacted hydrophobicity of the drug. between sempel with FeCl3 which form a red color to purple that previously Volunteers who have been given sempel diluted first with 95% ethanol eye drops previously performed bladder and precipitated with KCL and Na emptying aimed at the excretion of acetate and benzoyl chloride and reacted chloramphenicol eye drops can be with FeCl3 forming the compound into identified in the body. Urine, saliva and red to purple, from the above data it can tears taken before and after be concluded that chloramphenicol is chloramphenicol eye drops, results excreted through urine by means of obtained before chloramphenicol eye glomerular filtration and secretion. drops, urine and tear drops showed Within 24 hours 75-90% of oral doses negative results reacted with FeCl3 are excreted in the form of metabolites reagents did not show results as red to and 5-10% in the original form. purple as no occurrence of complexing between chloramphenicol and FeCl3. 4. CONCLUSION While on the sempel that has been given Drugs that enter the body will chloramphenicol eye drops taken every undergo pharmacokinetics process. saliva and urine taken 15 minutes once Basically pharmacokinetics is all the for 3 hours while for tears taken 30 process that the body does to drugs in minutes for 3 hours. In tamp and saliva the form of absorption, distribution, sempel produce negative data every seal metabolism (biotransformation), and because sempel does not form a excretion. Chloramphenicol is excreted complex red to purple bond with FeCl3, through the urine after going through this is due to the excretion of filtration processes in the glomerulus chloramphenicol through urine by and secretion processes. Within 24 glomerular filtration and secretion. hours 75-90% of oral doses are excreted in the form of metabolites and 5-10% in Ibrahim, UI-Press: Jakarta. hal. 157-163, 540-551. the original form. This is evidenced by 5. Connors, K.,A., 1992, Stabilitas the positive results reacted between the Kimiawi Sediaan Farmasi,jilid 1,Penterjemah: Drs. Didik sempel with FeCl3 which form a red to Gunawan, IKIP Press: purple color previously sempel first Semarang. hal. 9-40 6. P. Tangri and S. Khurana, diluted with 95% ethanol and “Basics of ocular drug delivery precipitated with KCL and Na acetate systems,” International Journal and benzoyl chloride and reacted with of Research in Pharmaceutical and Biomedical Sciences, vol. 2, FeCl3 which form complex to red to no. 4, pp. 1541–1552, 2011. purple . View at Google Scholar 7. Connors, K.,A., 1992, Stabilitas REFERENCE Kimiawi Sediaan Farmasi,jilid 2,Penterjemah: Drs. Didik 1. P. Pahuja, S. Arora, and P. Gunawan, IKIP Press: Pawar, “Ocular drug delivery Semarang. hal. 416-422. system: a reference to natural 8. Hardman, J.G., L.E. Limbird, polymers,” Expert Opinion on P.B., A.G. Gilman. Goodman Drug Delivery, vol. 9, no. 7, pp. and Gilman's ,The 837–861, 2012. View at Google Pharmacological Basis of Scholar Therapeutics. 10th ed. New 2. A. Rajasekaran, K. S. G. A. York, NY: McGraw-Hill, 2001., Kumaran, J. P. 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Description of Drug Information Service (PIO) of Pharmacy Study Program, Atma Jaya Catholic University of Indonesia During Covid-19 Pandemic Period of April - July 2020