تطوير ومراقبة مستحضر صيدلاني عيني مطول التأثير باستخدام تقنية النانو والتهلم في موضع التطبيق للجاتي فلوكساسين

الموضوعات

طب

روابط وملفات

التعريف والنوع

رقم الوثيقة

0ebf230b-b64e-4c7b-a34f-497b1f8fe882

رقم العقد

0

نوع الوسائط

Crawler

نوع المحتوى

الرسائل العلمية

صيغة المصدر

رسائل ماجيستير

نوع الملف

pdf text

أسماء الملفات

1963506_1.pdf

بيانات النشر

ترجمة العنوان

Development and Quality Control of a Sustained Release Ophthalmic Pharmaceutical Product Using Nano/In Situ Gelling for Gatifloxacin

ألقاب المؤلفين

[{"name_ar":"صالح طريفي ","title_ar":"اشراف","title_en":"Supervision"},{"name_ar":"عائدة محمد حجازي معاز","title_ar":"اعداد","title_en":"Preparation"},{"name_ar":"وسيم عبد الواحد","title_ar":"اشراف","title_en":"Supervision"}]

اللغة

Arabic

المصدر والدورية

اسم المصدر

تطوير ومراقبة مستحضر صيدلاني عيني مطول التأثير باستخدام تقنية النانو والتهلم في موضع التطبيق للجاتي فلوكساسين

المحتوى والصفحات

عدد الصفحات

173

ترجمة الملخص

n ocular drug delivery, the physiological constraints imposed by the protective mechanisms of the eye lead to poor absorption of drugs with very small fractions (<1%) of the instilled dose from conventional eye dosage forms (i.e., solution, suspension, and ointments) penetrating the cornea and reaching the intraocular tissues. And because ocular efficacy is closely related to ocular drug bioavailability ,many delivery systems were developed to improve classical aqueous eye drop formulations. Gatifloxac in (GFX) is in a class of antibiotics called Fluoroquinolones. It has been suggested as a promising novel broad spectrum antibacterial agent. GFX is used to treat bacterial conjunctivitis, it comes as an ophthalmic solution to be instilled in the eyes. It is usually instilled every 2 hours while awake (up to eight times a day) for 2 days, and then two to four times a day for 5 days. In our current work, we developed a new ocular pharmaceutical product for GFX with two different ocular delivery systems. The first one includes Nano\Micro Encapsulation to prepare polymericparticles loaded with GFX in order to have a sustained release, and the second technique isIn-situgelling system to disperse the prepared Nano\Micro particles within an aqueous liquid which can turn into stiff gel in the eye to provide mucoadhesive properties and improve precorneal residence time. Different procedures for polycaprolactone(PCL) Nano\Microparticles preparation were compared and the influence of various parameters of each process on colloidal properties (i.e. particles size, zeta potential, size distribution and Entrapment efficiency EE%) of the final particles prepared was investigated. The methods include: Nanoprecipitation, Simple Coacervation(Ionic gelation), Emulsion-Complex Coacervation, Emulsification solvent diffusion O/Wand Emulsification solvent extraction and\or evaporation O/W, W/O/W and O/O. Initially nanoparticles were prepared by Nanoprecipitation method and the developed nanosuspension was suitable for ophthalmic application with a mean particle size in the range of (184-207nm), zeta potential of (-32mV) and Entrapment Efficiency EE% of 40%. The prepared Microcapsulesby Emulsion-complex coacervation method was also suitable for ocular drug delivery, with a mean size (5-10 μm), and 54% encapsulation efficiency, but it was unstable and it showed phases separation after one day of preparation. Polycaprolactone microparticles were also prepared by using the double emulsion (water-in-oil-in-water) solvent extraction and/or evaporation method. Three different modified protocols were applied and the influence of their preparation parameters on the final microparticles properties was explored in an attempt to control particle sizes and encapsulation efficiency. By adjusting formulation and process parameters, we uncovered that using of 3% (w/v) PVA as emulsion stabilizer in the internal aqueous phase (second studied process) facilitated macro particles (77% of particles more than 100μm in size) which is suitable for oral drug delivery, but with highest entrapment efficiency EE% (82.12%). Whereas introducing 5% (w/v) of PVP as stabilizing agent and 5% (w/v) of NaCl as osmotic balancer in the external aqueous phase (third studied process) afford microparticles which is optimal in size for ophthalmic drug delivery (95% of particles less than 25μm in size) with an acceptable EE% (30.18%).The best results were obtained with Emulsification solvent evaporation O\O method with particle size in the range of (4-6μm), zeta potential was (-47mV) and EE% reached 100%, exhibiting a homogenous, stable and effective microsuspensi on suitable for ophthalmic application. The second stage of our work was to prepare In-Situ gel formulation depending on referenced preparations with improved mechanical and mucoadhesive properties that could provide prolonged retention time. Four different formulations with different polymers were evaluatedby using Poly (ethylene oxide)–poly (propylene oxide)–poly (ethylene oxide) (PEO–PPO–PEO, poloxamer®407) (as a temperature triggered polymer), Chitosan and Carbopol®940 (as a pH triggered polymer), Sodium Alginate (as ion activated polymer) and HPMC as a viscosity enhancing agent. An in situforming gel comprised of the combination ofPoloxamer®407with Chitosan with ratio (16:1) presented the best characterizations in terms of appearance, pH, tonicity, viscosity and gelling capacity .Then we combined both former for mulations and termed it as "Microparticlesladen in situ gel", by dispersinga specified quantity of drug loaded microparticles (equivalent to the prescribed dose of GFX0.3% w/v)in a specified volume of In Situgel base. Final formulation was tested for initial physicochemical characterization (i.e. particlesize, zeta potential, clarity, osmolarity, gelation capacity, pH, microbiological efficacy and in vitro release. We found that the formulation totally suitable for ocular delivery and there was no significant differences before and after microparticles loading. Thein vitro efficacy study indicated that Gatifloxac in retained its antimicrobial efficacy when formulated as a microparticles laden in- situgelling system and the drug was active against the selected strains of microorganisms. The in vitro release studies for final formulation were carried out using STF as the dissolution medium. Results indicated that the developed formulation showed better sustaining effect (28.6% during first 5hrs) without initial fast release of GFX, and the Regression Coefficients of zero order plots were found to be 0.9949.The next step of our research includes evaluating the efficacy of sterilization of the final developed formulation for In-vivo studies. Two referenced methods were applied and compared which are: Ultraviolet (UV) radiation and Autoclaving. And we found that UVirradiation is a plausible approach to provide a terminally sterilized PCL Microparticlesladen in situ geland the preparation being examined, therefore, passed the test for sterility. The accelerated stability study of the final developed formulation was performed at 40±2ºC temperature and 70±5% relative humidity for 3 months. The formulation was evaluated in terms of appearance, osmolarity, gelling capacity, pH, particlesize, zeta potential and drug content. No significant changes were observed after the first two months, except for average size decrease to 2μmm which might be due to slow polymer erosion. At the third month point,the formulation had light yellowish colorand it couldbe explained by the fact that, a part of drug may be released from microparticles into the outer dispersed phase. All other characterizationwere within the accepted limit. Also, the chromatographic analytical method for simultaneous determination of GFX in the developed formula was validated according to International Conference on Harmonization (ICH). The validation study showed that the HPLC method was; specific, linear, accurate and precise.So, by this research we tried to develop a new ocular pharmaceutical product has an extended an adherent properties for GFX, in order to enhance the bioavailability by increasing residence time in the eye and improve patient compliance by reducing required therapeutic doses

إشراف وإعداد

الإشراف

صالح طريفي , وسيم عبد الواحد

الإعداد

عائدة محمد حجازي معاز

الاقتباسات الببليوغرافية