Pharma courses

Pharma Admission

pharma courses

pharma admission

1.5 ANTIBIOTIC12,13,14
An antibacterial is a compound or substance that kills or slows down the growth of bacteria.

The word antibiotic comes from the Greek anti meaning 'against' and bios meaning 'life' (a bacterium is a life form). Antibiotics are also known as antibacterials, and they are drugs used to treat infections caused by bacteria.

A chemical substance derivable from a microorganism orproduced by chemical synthesis that kills or inhibitsmicroorganisms and cures infections known as antibiotic.

A broad-spectrum antibiotic can be used to treat a wide range of infections. A narrow-spectrum antibiotic is only effective against a few types of bacteria.

Antibiotics are drugs used to kill or harm organisms such as bacteria, viruses, funguses and protozoon in living organisms. Since their discovery in the 1930s, antibiotics have made it possible to cure diseases caused by bacteria such as pneumonia, tuberculosis and meningitis- saving the lives of millions of people around the world. Some antibiotics are produced from live organisms such as bacteria and funguses. Other antibiotics are totally or partially produced synthetically.

Antibiotics act via two mechanisms: they kill the microorganisms (bactericide action) and prevent them from reproducing (bacteriostatic action).

Classification of antibiotic
1. β-Lactam antibiotics
Examples: penicillins (e.g. amoxicillin),

2. Cephalosporins, carbapenems, monobactams, etc.

3. Tetracyclines
Example: tetracycline

4. Macrolide antibiotics
Example: erythromycin

5. Aminoglycosides
Examples: Gentamicin, Tobramycin, Amikacin

6. Quinolones
Example: Ciprofloxacin (a fluoroquinolone)

7. Cyclic peptides
Examples: Vancomycin, Streptogramins, Polymyxins

8. Lincosamides
Example: clindamycin

9. Oxazolidinoes
Example: Linezolid (Zyvox)

10. Sulfa antibiotics
Example: sulfisoxazole

Antibiotics are among the most frequently prescribed medications in modern medicine. Antibiotics cure disease by killing or injuring bacteria. The first antibiotic was penicillin, discovered accidentally from a mold culture. Antibiotics can help treat infections caused by bacteria but not by viruses.

Amoxicillin, an acid stable, semi?synthetic drug belongs to a class of antibiotics called the Penicillins (B?lactam antibiotics).

Subsequent need to adjust antimicrobial therapy in light of the laboratory results:15
Since different organisms vary in their susceptibility to antimicrobial agents, it is imperative that we have some means for determining the antimicrobial susceptibility of the infecting organism(s). Once the pathogen has been isolated, it can be subjected to susceptibility testing.

The commonly used disc-diffusion method is relatively simple to perform and is the most widely employed method. It provides semi quantitative or qualitative data about the susceptibility of a given organism to a given agent. The qualitative assessment of susceptibility is generally categorised as sensitive or resistant; however, some laboratories also report an intermediate category.

Quantitative data are also provided by methods that incorporate serial dilutions of antimicrobials in agar-containing or broth culture media. The lowest concentration of the antimicrobial agent which inhibits visible growth after an18 - 24 hour incubation period is known as the minimal inhibitory concentration (MIC). The minimum bactericidal concentration (MBC) is determined in broth dilution tests by subculturing samples without visible growth; this is based on 99.9% killing after 18 to 24 hours of incubation.

Testing the ability of the cultured pathogen to grow or not at a critical concentration (chosen to distinguish between sensitive and resistant bacteria), is a modification known as "breakpoint" testing. A recently described modification of the classical MIC test, the E-test, uses diffusion of a continuous concentration gradient of an antimicrobial agent from a plastic strip into an agar medium to yield quantitative measurements of antimicrobial susceptibility.

Monitoring Therapeutic response:15
In many patients, it is possible to monitor the therapeutic response on clinical grounds alone. Thus the subsidence of fever, the return of well-being, and the disappearance of both local and systemic signs of infection in the patient, all signify an appropriate response. No further formal monitoring is necessary in most cases.

An apparent failure to respond clinically may be due to either ineffectiveness of antimicrobial agent(s) (due to resistance or inappropriate route of administration) or to other reasons e.g. a localised infection that requires surgical drainage, or a superinfection etc. Careful reassessment is recommended when considering changes of antimicrobial therapy.

In certain situations, measurement of antimicrobial activity may be useful in predicting clinical response, e.g. determination of serum bactericidal activity (Schlichter test) in cases of infective endocarditis.

Pharmacokinetic properties of antibiotics:15
Knowledge of the pharmacodynamic and kinetic properties of antibiotics is imperative in choosing the correct antibiotic and correct dose. In order for antibiotics to exert their bactericidal or bacteriostatic activity, a few important principles pertain:
1.      Microbiological activity - antibiotic must bind to a specific binding site (e.g. ribosome or penicillin binding protein).
2.      Concentration of the antibiotic at the site of the infection is important (the higher the concentration the more binding sites are occupied on/in the bacterial cells).
3.      The antibiotics also have to remain on these binding sites for a sufficient period of time.
4.      Minimum inhibitory concentration (MIC): This concentration represents the minimum amount of drug with which the bacteria have to come into contact, in order for the antibiotic towork.

Pharyngitis and tonsillitis are defined as acute inflammations involving the posterior pharynx and the tonsillar pillars. The most common bacterial cause of pharyngitis and tonsillitis is group A beta-hemolytic streptococci. For regulatory purposes, it has been customary to request the actual species be identified (i.e., Streptococcus pyogenes).

Pharyngitisis an inflammationof the throator pharynx, In most cases it is quite painful, and is the most common cause of a sore throat. Pharyngitis can result in very large tonsilswhich cause trouble swallowing and breathing. Bacteria responsible for pharyngitis:-Streptococcus spp.

Tonsillitisis an inflammationof the tonsilsmost commonly caused by viral or bacterial infection. Symptoms of tonsillitis include sore throatand fever.

Signs and symptoms characteristic of pharyngitis/tonsillitis should include the following:
*    A sore and scratchy throat, pain on swallowing (odynophagia), temperature, chills and/or fever.
*    The pharyngeal mucosa should be erythematous to fiery red, and a thick exudate should cover the pharynx and tonsillar area.
*    Uvular edema may be noted.
*    Cervical adenopathy should be present and commented on.
*    A white count over 12,000 may be present.
*    Strains of S. pyogenesthat elaborate erythrogenic toxin may cause a scarlet fever rash of the face and skin folds, red tongue and prominent papillae (strawberry tongue).
*    sore throat
*    fever - either low grade or high
*    headache
*    decrease in appetite
*    not feeling well
*    nausea
*    vomiting
*    stomach aches
*    painful swallowing
*    visual redness or drainage in the throat

Objective Data:18

The following assessment is suggested, and any or all of these findings may be noted:
*  Temperature:
The temperature is usually >100.5 degrees F in streptococcal infections and is usually <100.5 degrees F in viral cases.

*  Skin:
Inspect for a rash. Occasionally a diffuse, erythematous rash with petechiae, which starts  on the neck and extends downward, accompanies streptococcal infections.

*  Oropharynx:
Inspect for redness, inflammation and exudates of the pharynx, uvula and tonsils. Exudate is more common with streptococcal infections.

*  Neck:
Palpate for lymphadenopathy. Swollen and tender anterior cervical nodes are more often seen in streptococcal infections.

*  Ears:
Perform an otoscopic examination. The examination is usually normal in isolated tonsillopharyngitis.

Pharyngitis and tonsillitis diagnosis:19
In most cases, it is hard to distinguish between a viral sore throat and a strep throat based on physical examination. It is important, though, to know if the sore throat is caused by Group A Beta Hemolytic Streptococci , as this requires antibiotic treatment to help prevent the complications that can occur with these bacteria.

As a result, most people, when they have the above symptoms, will receive a strep test and throat culture to determine if it is an infection caused by Group A Beta Hemolytic Streptococci. This usually involves a quick throat swab in the physician's office.

Quick tests, called rapid strep tests, may be performed. This may also immediately become positive for Group A Beta Hemolytic Streptococciand antibiotics will be started. If it is negative, part of the throat swab will be kept for a throat culture. This will further identify, in two to three days, if there is any Group A Beta Hemolytic Streptococcipresent. Physician will decide the treatment plan based on the findings.

Treatment for pharyngitis and tonsillitis:19

Specific treatment for pharyngitis and tonsillitis will be determined by your physician based on:
*  Your age, overall health, and medical history
*  Extent of the condition
*  Cause of the condition
*  Your tolerance for specific medications, procedures, or therapies
*  Expectations for the course of the condition
*  Your opinion or preference

If bacteria are not the cause of the infection, then the treatment is usually directed more for comfort. Antibiotics will not help treat viral sore throats. Treatment may include:
*  Acetaminophen (for pain)
*  Increased fluid intake
*  Throat lozenges
*  Antibiotics (if the cause of the infection is bacterial, not viral)

Various study reports showed that amoxicillin was effective against variety of micro?organisms with MIC ranges 0.06 μg/ml?4 μg/ml for most of the micro?organisms. The absolute time unbound amoxicillin concentrations remained > MIC value of 0.06 μg/ml was ≈ 13 hours in healthy subjects. For Escherichia coli, the kill rates were higher with amoxicillin than with ampicillin with exponential bactericidal response. With an antibiotic half?life of 1 hr, the amoxicillin first order inactivation rate was 3.544 hr?1and the viable cell half?life was 0.196 hr; the respective values for ampicillin were 2.341 hr?1and 0.296 hr.For Staphylococcus aureus, the rates of kill were similar with both agents, but, amoxicillin had a long bacteriostatic phase which was not seen with ampicillin.  This led to a longer lasting antibacterial effect and reduction to a lower total count with amoxicillin.20

In treating a bacterial infection, the amoxicillin product is formulated to provide a concentration of amoxicillin in the plasma that is above the MIC of the bacterial pathogen for a period of time each day that is effective for treating the bacterial infection.21

Table 1.1: Minimum Inhibitory Concentration of amoxicillin of several clinically important micro-organisms.22

In vitro activity

Average minimal inhibitory concentration (MIC)

0.01-0.1 mcg/ml

0.1-1 mcg/ml

1-10 mcg/ml

Gram-positive micro-organisms

Str.β haemolyticus
Str. α haemolyticus
Str. pneumoniae
Cl. tetani
Cl. Welchii

Staph. aureus(penicillinase negative)
B. anthracis
B. subtilis
Listeria monocyto-genes

Str. Faecalis

Gram-negative micro-organisms

N. gonorrhoeae

H. influenzae
Bordetella pertussis

E. coli
P. mirabilis
S. typhi
Sh. Sonnei
V. cholerae

The amoxicillin is the antibiotic agent. The main objective of present work is to formulate modified release dosage form of amoxicillin wherein its release is modified over conventional release. Such modified release formulations have been found to improve the bactericidal effect of drug on Pharyngitis/Tonsilitis. The modified release dosage form has the advantage that the total dose of amoxicillin decreases over conventional dosage form. They increase the patient compliance. Hence in this work objective is to formulate modified release system for in order to check plasma concentration profile for 24 hrs. and try to achieve the same.

The aim of this work would be to design and evaluate modified release dosage forms containing antibiotic agent.

Broadly, the work would endeavour to achieve the following objectives:
1)      To prepare different modified release dosage form of amoxicillin for the treatment of pharyngitis/tonsillitis.
2)      To study the Preformulation factors such as melting point, drug-excipients interaction, angle of repose, carr’s index, drug property etc.
3)      To characterize manufactured tablets for hardness, thickness, content uniformity, weight uniformity, dimensions, etc. and capsule for weight uniformity, content uniformity, appearance.
4)      To study in vitro drug release study comparison of different dosage form like tablet, capsule.
5)      To study in vitro drug release study of different dosage form with marketed product in US or with the ideal theoretical drug release profile.
6)      To carry out short term accelerated stability studies on the most satisfactory formulation as per ICH guidelines.



Subscribe to PharmaTutor Alerts by Email