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العنوان
Pharmaceutical and clinical evaluation of antifungal oxiconazole solid lipid nanoparticle formulation /
المؤلف
Ahmed, Rabab Ahmed Mahmoud.
هيئة الاعداد
باحث / رباب أحمد محمود احمد
مشرف / أمل كمال حسين
مشرف / هبة فتحي منصور
مشرف / غادة علي ناصف
الموضوع
Pharmacology. Clinical pharmacology. Pharmacology, Clinical.
تاريخ النشر
2020.
عدد الصفحات
162 p. :
اللغة
الإنجليزية
الدرجة
ماجستير
التخصص
الصيدلة ، علم السموم والصيدلانيات
تاريخ الإجازة
1/1/2020
مكان الإجازة
جامعة المنيا - كلية الصيدلة - الصيدلة الاكلينيكية
الفهرس
Only 14 pages are availabe for public view

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Abstract

The skin provides an effective barrier to protect the body from the penetration of molecules and micro-organisms in the external environment, and from excessive loss of water to maintain homeostasis. The main skin barrier is the stratum corneum, due to its unique structure of flattened corneocytes which are surrounded by lipid bilayers and ceramides (Scheuplin , 1996). Penetration of most topically applied compounds follows the intercellular tortuous route of the stratum corneum lipid bilayers (Blank et al., 19971), and the transcellular route through the corneocytes in some circumstances (Kasting et al., 1971).
Although hair follicles and sweat glands account for only about 0.1% of the total skin surface area these appendages are potential routes of access into the skin, and may be important for nano systems penetration(Illel et al., 1991).
Nano systems that have been investigated for enhanced skin permeation include micro emulsions (ME), nano emulsions (NE), nanoparticles of various compositions including solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLC), liposomes and vesicles(Pastore et al., 2017).
SLNs enhance skin permeation by prolonging contact with the skin surface, providing an occlusive barrier that hydrates the skin, and interacting with the lipids in the stratum corneum bilayers.
These nano systems can offer significant advantages in the formulation of hydrophobic drug, as oxiconazole, enhancing their solubility and bioavailability.
Compounds that successfully diffuse across the stratum corneum are relatively small (up to about 500 Da), lipophilic (log P 1–3) and water soluble, thus excluding many potentially useful therapeutic compounds with properties that do not fit these criteria. A range of micro- and nano systems have been investigated as potential delivery vehicles that could enhance the skin penetration of both small and macromolecules that cannot permeate the stratum corneum in sufficient quantities to provide a therapeutic outcome. This approach formulated hydrophobic solid lipid oxiconazole nitrate nanoparticles composed of lipids that are solid at room temperature with a surface covering of surfactants to stabilize them as a nano-dispersion (Muller et al., 2002).
Here, in the present study, we developed a new SLNs gel system of 129 nm particle size and enhanced sustained drug release (Daneilson and lindman, 1981).
The work in this thesis was divided into three chapters as follows:
Chapter 1: Preparation And In-vitro characterization of oxiconazole loaded nanoparticles formulations

This chapter dealt with the preparation of oxiconazole nitrate loaded nanoparticles using solvent diffusion emulsification technique. Different surfactants were used for the preparation of SLNs like tyloxapol, poloxomer 407, tween 80 and co-surfactant as sodium deoxy cholaote.

The influence of different formulation parameters of this method was investigated, along with the effect of additives. These parameters include surfactant type, lipid concentration, lipid concentration and homogenization time.

The produced SLNs were characterized by scanning electron microscope (SEM), particle size analysis, entrapment efficiency (EE%), drug release study.
It was found that oxiconazole nitrate SLNs prepared using tyloxopol (0.5%w/v), tween80 (0.5%w/v), poloxomker 407(1%w/v) showed the highest entrapment than other surfactant concentrations used.

from these results it can be concluded that EE% increased with the increase of surfactant concentration, and lipid concentration but to a certain limits.

Scanning electron microscope results showed that most SLNs formulations had smooth surfaces with spherical shape. While SLNs prepared using high lipid content had rough surface.
Zeta potential of the optimized SLNs preparation was found to be -61.6 indicating high stability of the optimized formulation.
Chapter 2: Formulation and characterization of oxiconazole nitrate loaded SLNs carbopol gel system
This chapter described the formulation and evaluation of skin delivery system of oxiconazole nitrate, based on incorporation of SNs in carbopol gel system.
The clarity, pH, and drug release profiles of the developed formulations were studied, all formulations exhibited pseudo plastic viscosity. The clarity, and pH of the formulations were found to be satisfactory.
The developed formulations provided more sustained release than the marketed cream preparation, over 12 hrs. period. Proving the effect of SLNs when incorporated in carbopol gel to increase the release time.
Chapter 3: The human study
This chapter aimed at human study evaluation of the produced SLNs gel best formulation.
The obtained results for the prepared system were compared with the marketed product. The study was conducted on 28 patients of different tinea infection selected from the outpatient clinic of Dermatology Department of Minia university, Their age ranged from 12 to 50 years.
group 1 was composed of 14 patients who were treated with marketed oxiconazle cream for 4 weeks for tinea pedis and 2 weeks for other types of fungal tinea infections. Nine cases assessed mild result (64.2%).

Four patients assessed moderate result (28.57%). One patient assessed good result (7.14%). None of patients treated with tinox assessed excellent evaluation (0%).

group 2 was composed of 14 patients who were treated with the new oxiconazole SLNs gel formulation, they were treated for 4 weeks for tinea pedis infection and two weeks for other types of tinea fungal infection. nine patients treated with the new formulation assessed excellent result (64.2%). Four cases assessed good result(28.57%). One assessed mild result(7.14%). None assessed moderate result(0%).