الفهرس 
AcknowledgementOnly 14 pages are availabe for public view
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Abstract
ointment) and G1 (Na-CMC gel base) had shown the best release of the drug and therefore they were further selected to investigate the effect of cosolvency and solid dispersion on nalidixic acid release. Both when used separately had enhanced nalidixic acid release but the highest result was obtained by combining both in formulae (W8, E8 and G16).
Kinetic analysis of the release data
The kinetic analysis of release data of nalidixic acid from different topical preparations had shown that its release from hydrocarbon, absorption and emulsion ointment bases was best fitted by Higushi diffusion model while zero order was the best fitted model for nalidixic acid release from water soluble ointment bases and gel bases.
Compatibility study
DSC thermograms and IR spectra of nalidixic acid, excipients and their physical mixtures showed that the drug is compatible with the excipients of the selected formulations.
Antibacterial activity study
The antibacterial activity of the selected nalidixic acid formulation was assessed using agar plate diffusion method. It was found that the higher release rate, the larger the inhibition zone. In all tested formulations, the presence of cosolvency and solid dispersion had shown larger inhibition zone compared to formulae (E3, W5, G1) containing neither of them. All cream preparations (E3, E6, E7, and E8) had shown weak antibacterial activity. Accordingly, nalidixic acid cream formulations were excluded. Gel and water soluble ointment bases were further investigated for their stability.
Stability study
No significant change in pH or drug content had been observed when stored formulations checked monthly. All stored formulations had retained acceptable cosmetic and aesthetic criteria. All the above indicates that the drug is stable in the selected formulations. The stability was further checked by thin layer chromatography. All the obtained results had strongly recommended the selection of Na-CMC gel base and water soluble ointment base for clinical application on patients with impetigo.
Chapter ІІІ
Clinical application of selected nalidixic acid topical formulation in impetigo
Impetigo, the most common bacterial infection in children, was selected for our study.
Skin irritation test
Before clinical application of selected nalidixic acid topical formulations, skin irritation test was performed on the shaved back of rabbit. The test was performed for medicated ointment and gels as well as plain formulations. No redness or erythema had resulted upon the application of any of the tested formulation. This indicates that no skin irritation is expected upon their clinical application.
Clinical application in impetigo
The protocol of the work was approved by the Medical Ethics Committee of the Faculty of Medicine, Assiut University. The clinical study was conducted on 25 patients at the Dermatology department Assiut University Hospital. The patients were divided into five groups, each consisted of five patients. In group I, patients received ointment containing 1 % nalidixic acid (W5). While in group II, patients received ointment containing isopropanol and nalidixic acid-sodium benzoate solid dispersion equivalent to 1 % drug (W8). Group III included patients who received gel containing 1 % nalidixic acid (G1) while in group IV, patients received gel containing isopropanol and nalidixic acid-sodium benzoate solid dispersion equivalent to 1 % drug (G16). Group V was kept as control and patients received placebo ointment and gel. All patients were instructed to apply the formulation twice daily for 7-14 days. The clinical outcome had demonstrated generally the effectiveness of nalidixic acid topical formulations and specially that of gel containing isopropanol and nalidixic acid - sodium benzoate solid dispersion in treatment of impetigo. Colored photographs were taken for patient before and after treatment in order to assess the degree of response to the therapy. It is worth mentioning that none of the tested formulations had shown any adverse effects on any patients. In addition the short period of treatment and the ease of application had increased patient compliance and adherence to treatment. All obtained results strongly recommends the utility and the efficacy of G16 (gel containing isopropanol and nalidixic acid-sodium benzoate solid dispersion) in the treatment of impetigo.