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Pharmaceutical Evaluation of Metronidazole Tablet With Hplc Method Validation

Thesis Info

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Author

Kashif Ali Safdar

Program

PhD

Institute

University of Karachi

City

Karachi

Province

Sindh

Country

Pakistan

Thesis Completing Year

2015

Thesis Completion Status

Completed

Subject

Pharmaceutics

Language

English

Link

http://prr.hec.gov.pk/jspui/bitstream/123456789/13499/1/Kashif_Ali_Safdar_Pharmaceutics_2015_HSR_UoK_Karachi_02.01.2017.pdf

Added

2021-02-17 19:49:13

Modified

2024-03-24 20:25:49

ARI ID

1676726865480

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The choice of an analytical method is usually governed by the intrinsic analytical properties of the drug molecule or its amenability to chemical derivatisation to render it compatible to quantitation. The reliability of the quantitation depends on these analytical techniques. Currently, reversed phase high–performance liquid chromatography with UV detection represents the analytical method of choice for the quantitative determination of raw material, in-processes formulation, finished products as well as in the biological matrix. Metronidazole is one of the most effective and clinically very useful and popular antibacterial agent which also possess antiprotozoal action. The clinical importance of these agent is continuously increasing with the passage of time, as the infections are caused by the different pathogens/microorganisms. In the proposed study first developed the analytical method for the determination of metronidazole then validate it for the evaluation of pharmaceutical property of different brands of metronidazole 200mg and 400mg available in the local market as per ICH guideline. The parameters that used for the validation were specificity, linearity, accuracy, precision, lower limit of detection, quantitation and stability of drug in mobile phase as well as in biological matrix. The mobile phase was comprised of 0.01 molar potassium dihydrogen phosphate buffered at pH 3.0 and acetonitrile in ratio of 83: 17. The drug was eluted from C18 column (5µm; 250 mm X 4.6 mm). The % RSD of peak areas of metronidazole was 0.03% and the mean retention time of six consecutive injections was 5.333 minutes. The LOD and LOQ of the method was 8.14ng/mL and 32.56ng/mL respectively. The drug was stable in mobile phase as well as in plasma up to 28 days that shows the method can be used successfully not only for the raw material and finished product but also for pharmacokinetic study in human. A new formulation (ODT) was developed with the use of different super disintegrants such as sodium bicarbonate and crospovidone. Comparison of disintegration and friability of the tablets showed that the tablet with crospovidone is more close to our objective. The optimization study was performed with the aid of software “DesignExpert 9.0.1, State Ease Inc.” The amount of crospovidone and HPMC per batch were taken as independent variable to assess their effect on the disintegration time and friability of the formulation. Central composite design was selected for optimization process and number of batches were prepared. The amount of X1 (Crospovidone) and X2 (HPMC) predicted by the software with the desirability of 1.0 were 37.76mg and 16.71mg respectively. A check point batch were prepared based on these predicted amounts to confirm the validity of the design for this optimization process. The results revealed that by increasing the concentration of crospovidone in formulation decreases disintegration time of tablets which is quite expected as it enhances the wicking property of the formulation. Similarly, it was also observed that increase in concentration of HPMC significantly decreases the % friability of the tablets as it improves the cohesive binding forces. The check point batch was subjected to stability studies after blistering for 06 months. All the tests performed as per USP for the physicochemical and stability evaluation periodically at time interval of 3 months and 6 months. The results were then compared with the initial results to evaluate the stability characteristics of the formulation. The results showed no significant differences at time intervals of 0, 3 and 6 months. Hence the formulation found to be well stable under the recommended conditions (temperature: 40 ± 2°C & % RH: 75 ± 5%). The friability was between 0.47% - 0.50%, disintegration time was between 15 – 16 seconds and in vitro dissolution at three different time intervals i.e. 0, 3 and 6 months were between 98.08 - 98.29% during the entire period of stability studies. No significant variation observed in content assay of stability batch throughout the study period. The CDP of metronidazole 200mg, 400mg brands and formulated tablets were performed in three dissolution mediums i.e. pH 1.2 buffer, pH 4.5 buffer & pH 6.8 buffer. The samples were withdrawn at different time intervals i.e. at 10, 15, 20 and 30 minutes and absorbance was taken at λmax 278.0 nm. Percent dissolution calculated with the help of Microsoft excel add-in “DD Solver” v1.0 found to be ≥ 85% within 15 minutes which indicates that dissolution is not a rate limiting step in the bioavailability of these tablets. Different dissolution models were also applied to verify the drug release pattern between the marketed and formulated drug and it was found that the pattern release of the formulated tablets is same as that of the marketed and innovator brands
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97. Al-Qadr/Great Eminence

97. Al-Qadr/Great Eminence

I/We begin by the Blessed Name of Allah

The Immensely Merciful to all, The Infinitely Compassionate to everyone.

97:01
a. Indeed, WE began sending this down – The Qur’an –during the later part of the Night of Great Eminence.

97:02
a. And what will enable you to perceive the value, honor, magnificence of the Night of Great Eminence?

97:03
a. The Night of Great Eminence is better than the nights of a thousand months of worship and meditation.

97:04
a. The Angels descend in it and the Spirit - again and again - by the Command of their
Rabb - The Lord, for every matter of significance.

97:05
a. Spiritual peace of the Night prevails till the rising of the dawn.

Concept of Islamic Leadership in Syed Muhammad Naquib Al-Attas’s Philosophy

Islamic leadership is defined as a divine trust (amanah) from Allah, based on the Tauhidic paradigm of oneness of Allah that is focusing to serve HIM as HIS servant, while at the same time be the servant of Allah, perform the role of Khalefah (vicegerent) of Allah fully adheres to the Sunnah central to Islamic personality, characteristics and aklaq (Islamic moral and ethical) that was exemplified by the prophet (s.a.w), leading followers to the organization goals and to the straight path of the success in the Hereafter. It is based on this adopted definition that the paper tries to look into the notion from perspective of a Malaysian Muslim Philosopher to the core, Syed Muhammad Naquib Al-Attas, who believes in delivering amanah given to him, and at the same time perform the role of vicegerent of Allah. He suggests that lack of good leaders or rise of unqualified and false ones is one of the major problems of Ummah. Content analysis approach is engaged on both primary and secondary data collected. That is to say, it is a qualitative research in nature. The finding shows that the basis of Al-Attas’s concept of leadership is entrenched in Al-Qur’an and the tradition of the prophet in addition to his deep understanding on the Islamic Sciences such as Islamic theology, philosophy, and metaphysis and so on.

Molecular Epidemiology of Campylobacter Species Isolated from Meat Source in Lahore - Pakistan

Thermotolerant Campylobacter, one of the well-known bacterial causes of foodborne illnesses in humans, worldwide. These bacteria are gram-negative short rods which grow under microaerobic conditions and are non-spore forming. Campylobacteriosis is characterized by diarrhea, abdominal pain, cramps and fever. The diarrhea may be associated with blood and can be accompanied by vomiting/nausea. Digestive tract of all warm blooded animal is a significant reservoir for Campylobacter species. Campylobacter causes huge economic losses to a country by restricting trade in international market for meat and meat products. A total of 600 meat samples were collected from three different species (i.e., Beef (n=200), mutton (n=200) and poultry (n=200)) during September 2014 to February 2015 from ten administrative towns of district Lahore (Pakistan). From each town 20 samples of each species were collected through convenience sampling method thus from each town 60 samples and from 10 towns 600 samples were collected for this study. Data regarding factors associated with Campylobacter were collected through a pre-designed questionnaire. The collected samples were transported at 4˚C to laboratory of Epidemiology & Public Health department for further processing. The ISO 10272-1:2006 (E) was followed for the conventional microbiological isolation and confirmation of Campylobacter species. DNA was extracted with the help of Qiagen kit and DNA was quantified by Nanodrop C2000 (Thermo Scientific). The isolated strains (in 20% glycerol) and the extracted DNA were stored at -80˚C and -20˚C, respectively. Real Time and multiplex PCRs were optimized for molecular detection and identification of Campylobacter species in meat. Sangar method was used for sequencing of the genes and phylogenetic trees were generated with the help of Mega 6.0 software. The isolated strains were characterized by MLST (Multi Locus Sequence Typing) according to protocol described by pubmlst.org.com. The identified sequences were processed, entered and queried to PubMLST data base for comparison with already existing Campylobacter species alleles to obtain specific allelic numbers and sequence types (STs) for our isolates (http://campylobacter.mlst.net/). Antibiotic susceptibility tests for selected isolates were performed according to the Kirby-Bauer method. Chi square test was applied to see the association of various factors with Campylobacter strains circulating in meat sources in Lahore. A total of 125 Campylobacter isolates were recovered from 600 meat samples. The percentage prevalence was 20.8%. Campylobacter isolates were frequently present in poultry meat, followed by mutton and beef with 29%, 18% and 15.5%, respectively. Campylobacter jejuni was isolated from 93 meat samples and C. coli from 32 samples. The prevalence of Campylobacter in poultry was 29% (58/200). In these positive samples C. jejuni was frequently isolated (38/58) as well as C. coli (20/58). From mutton out of 200 samples, 36 were found positive for Campylobacter species. Campylobacter jejuni was isolated from 69.4% (25/36), C. coli 30.6% (11/36). A total of 31 samples were positive for Campylobacter isolates. The contribution Campylobacter jejuni and Campylobacter coli in beef was 61.2 % (19/31) and 38.8% (12/31), respectively. MLST analysis of 3 Campylobacter jejuni and 3 Campylobacter coli isolates yielded 2 different STs (i.e., 5 ST 1769 belongs to 828 CCs and 1 ST 2282 belongs to 206 CC). The highest resistance was observed against enrofloxacin 79.2% (99/125), followed by tylosin 77.6% (97/125), ciprofloxacin and amoxicillin 71.2% (89/125), colistin 69.6% (87/125), neomycin 32.8% (41/125), nalidixic acid 31.2% (39/125), gentamicin 25.6% (32/125) and doxycycline 8.8% (11/125). Thus doxycycline (91.2%) was found drug of choice followed by gentamicin (74.4%), nalidixic acid (68.2%) and neomycin (59.2%).