الفهرس 
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Abstract
Part I:
This part contained a general introduction, chemical name, structures, molecular formulae and weights, physical properties, dissociation constants (pka), pharmacological actions and uses of the studied drugs.
It also contains literature review for the pharmacopoeia and other reported methods of analysis for the selected drugs.
Part II :
This part dealt with the development and validation of a new analytical procedure for the simultaneous determination of nine penicillins of different classes of penicillins.
These areincluding amoxicillin, ampicillin, clavulanate, flucloxacillin , penicillin Gbenzathine, pipe-racillin, sulbactam, sultamicillinand tazobactam in their mixture where the developed method used reversed phase C18 column with gradient elutionat a flow rate of 1.5 mL min-1with UV detection at 220 nm and a mobile phase composed of methanol: phosphate buffer operating at pH 4.0.
The proposed HPLC method was statistically validated with respect to linearity, ranges, precision, accuracy, selectivity and robustness to satisfy International Con-ference on Harmonization regulatory requirements.
The proposed method can be recom-mended for the routine quality control of the studied drugs either in cross contamination with non-penicillin facility or in monitoring facility surface cleaning, in addition to environmental application such as in air pollution and wastewater in penicillin facility with high accuracy and precisionas mentioned in Part III and IV
<Part III:
This part dealt with simple and easy HPLC method to identify and determine trace amounts of penicillin drugs in non-penicillin drugs in their pharmaceutical dosage forms. These arebiperiden tablet, formoterol inhaler capsule, miconazole cream, omeprazole cap-sule and salbutamol syrup and respiratory solution.
These drugs wereselected for studying thecross-contamination with penicillins.
The challenge in this work was to separate nine penicillins of different classes of penicillins from non-penicillin drugs in pharmaceutical dosage formsthat have different co-formulated excipients with good chromatographic pa-rameters and with high purity profiles, taking into consideration the small concentrations of penicillins.
The proposed method was successfully applied to the analysis of the trace amounts of penicillins in non-penicillin products in the pharmaceutical dosage forms.
In ad-dition, the validation of the proposed method according toICH guidelines.
The results obtained for each compound were in a good agreement with label claims and the results obtained from the proposed chromatographic method were compared statis-tically with other official methods using Student’s t-test (for accuracy) and the variance ratio F-test (for precision).
In addition, the results obtained from the standard addition method confirm that there is no interference from co-formulated excipients with the results of the proposed method.
It is evident from these results that the proposed method is applicable for 113the assay ofthe non-penicillin drugs in their pharmaceutical dosage forms in presence of trace amounts of penicillins with good levels of accuracy and precision.
Part IV :
This part comprised the study of residues of the active pharmaceutical ingredients of penicillin drugs for ensuring the efficiency of cleaning validation on different equipment surfaces, floors and walls.
In addition, analysis of the studied penicillin drugs in environ-mentalair and waste water samples of the penicillin plant we reperformed in order to reach a safe environment for a high-quality pharmaceutical product characterized by high purity and effectiveness.
The same time protection of the workers in the production area from any adverse side effects and the environment surrounding the factory from any adverse environ-mental effects.
For ensuring efficiency of cleaning validation, after cleaning equipment surfaces used for preparation of a penicillindosage form,swabbing samples from the equipment surfaces as well asfrom the floors and wallssurfacesof penicillin plant, were collected and analyzed by proposed method.
The results obtained from these samples showed that the active ingredient was not detected or below the of the limit of detection of our proposed method.Meanwhile, for environmental application,penicillin residuesin air samples were col-lected from the area of exposed groupin the preparation room, the space around the mixing equipment and filling machines.
Dust residues were collected on a weighed filter and it was re-weighed after sample collection, extracted and analyzed by the proposed HPLC-DAD method.
The results of this study showed that the mean concentration of total dust, active penicillin dust and TWA in the oral suspension and tablet production lines were 4.15±0.05mg/m3, 5.99%±0.03 and 4.15±0.05mg/m3, respectively.
The mean total dust concentration in the penicillin vial linewas 1.37±0.0.15 mg/m3and% of ampicillin and sulbactam active material residuesin the total air dust were3.07±1.10% and 1.53±0.55, respectively and Time-Weighted Average (TWA) exposure for penicillin dust was 1.37±0.15mg/m3.
These results obtained in this study were lower than the limits permitted levels that prove the effi-ciency of the proposed method for these kinds of routine analysis.
In waste water samples an appropriate volume of wastewater was filtered through 0.45-μm glass-fibersyringe filters in order to avoid extraction inefficiencies and then the solutions were analyzed by HPLC-DAD.
The results obtained from the samples drainage from peni-cillin plant which were examined by HPLC_DAD was free from the nine studied penicillin drugs