Formulation of Nystatin 2.4%, Neomycin Sulfate 0.35%, Dexamethasone 0.05% (w/w) Ointment

The aim of study is production of new local drug consisting of Nystatin, Neomycin sulfate, Dexamethasone ointment are veterinary medicinal preparations used in the treatment of exogenous fungi and infections in small and large animals that cause by ( candida albicans ) and affected by gram positive and gram negative bacteria like ( Staphylococcus aureus, Escherichia coli, Haemophilus influenza, Klebsiella-Enterobacter species, Neisseria species, and Pseudomonas aeruginosa). Nystatin is considered one of the safe drugs when treating external fungal infections in field animals. Neomycin works by inhibiting protein synthesis in the bacterial cell and thus leads to the killing of bacteria either dexamethasone works to stop infections in the affected area of animals. In order for this product to be both research and applied, many of the initial pharmaceutical compositions were prepared until the final and stable composition was reached in this form. (90-110% permissible limit of activity). This process included several stages of collecting information on the substances included in the formula, active substances and additives, and then preparing the formula according to the specifications. International pharmacology using pharmacopoeia, followed by a study of stability and resistance of the preparation at room temperatures, then sending samples for field examination to the veterinary department and for the lack of cases for other animals where it was used on cases of fungal infections and skin infections in small animals (Cats). The treatment period was 5-10 days, and it brought very good results, according to the field evaluation form attached to the research. Outcomes of study its good and new research and very important to treatment skin infection in small animals.


Introduction
Nystatin, Neomycin sulfate, Dexamethasone ointment are very important preparations in the treatment of cases infected with external fungi such as Candidiasis caused in particular [candidiasis albicans] or any fungus of the family of candida genus [Psychia], which causes various infections ranging from superficial infection limited on Iraqi Journal of Industrial Research (IJOIR) Journal homepage: http://ijoir.gov.iq the skin or on the mucous membranes [1], where it has an important role in skin and subcutaneous infections in dogs, cats and birds [2] and skin infections caused by gram-positive and gram-negative bacteria such as Staphylococcus aureus, Escherichia coli, Haemophilus influenzae, Klebsiella-Enterobacter species, Neisseria species, and Pseudomonas aeruginosa [3].
Nystatin: antifungal belonging to the polyene group. It is a pale yellow substance in the form of a powder. Like other antifungals, nystatin is of bacterial origin. It was isolated in1950 by Elizabeth Lee Harren of a bacterium called Streptomyces Noursei [5]. Nystatin is a known antifungal from the polyene family. Due to Nystatin limited solubility and high toxicity, it is used mainly to treat oral and dermal fungal infections [6]. It has a therapeutic role for many fungi and yeasts, including Candida [7]. It has an effective role in killing and inhibiting the growth of fungistatic and fungicidal by working on degenerative changes in the walls of fungal cells and its association with ergosterol, which is an essential element in the membranes of fungal cells found in genera the candida specious which leads to holes in the cell walls and thus leakage of potassium and the exit of the rest of the components from inside the cells to outside the cells, which leads to the death of the germ cell [8].

Neomycin Sulfate
An antibiotic belonging to the group of aminoglycosides belonging to the streptomycin family. It is a white to yellowish powder that dissolves quickly in water and has a broad spectrum action against Gram-negative bacteria such as: Salmonella, Proteus, klebsiella, E. coli, Enterobacter. Neomycin was discovered in 1949 by microbiologist Selman Waksman and his student Hubert Lechevalier at Rutgers University. Neomycin received approval for medical use in 1952 [9]. It is produced naturally by the bacterium Streptomyces fradiae [10]. Synthesis requires specific nutrient conditions in either stationary or submerged aerobic conditions. The compound is then isolated and purified from the bacterium [11].
Mechanism of action -Neomycin kills and inhibits the action of the bacterial cell by inhibiting the formation of the bacterial cell wall by preventing the binding of trans Peptidation to Peptoglycol, which is the main component of the bacterial cell wall, thus increasing the activity of enzymes degrading the cell wall. By a process known as autolysis) Hydrolasesnureintolysins) [12].

Methodology
The examination was carried out in the laboratories of Al-Razi Research Center and the acceptance certificate was obtained by the above center. Other forms were also sent for the purpose of conducting the field assessment. The results were good and the acceptance certificate was obtained by the Veterinary Department of the Veterinary Hospital.
Procedure: Weighing the raw materials and ingredients by the quantities indicated for each of them to prepare (100) g. Preparing (100) grams of the ointment as follows:

Results and Discussion
The results of the microbiological examination showed the effectiveness of the preparation from a biological point of view, and this was confirmed by the results of the examination in the microbiological laboratory at the Ibn Sina Research Center, where its effectiveness was (100%) and it is within the constitutional limits of veterinary pharmacopoeia (90-110%). A stable and stable composition was reached by studying the stability at different temperatures at (25, 35) °C for a period of 3 months (Table 2), where it was noted that the effectiveness of the preparation is not affected much over time, because the effectiveness of nystatin remained within the permissible limits and the decrease in effectiveness was very limited. This indicates the stability and effectiveness of the drug combination. The field examination also showed its therapeutic efficacy for cases of fungal diseases and skin infections in cats. The opposition obtained a certificate of acceptance send from the veterinary department / veterinary hospital.

Stability study
The stability of the product was monitored at room temperature for a period of (3) months, according to the results listed below. Initial evaluation (time zero) 100% according to the microbiological examination [14].

Conclusions
We conclude from the results that the physical and chemical specifications of the final formula were fixed during the period of the stability study. It is recommended to use the preparation as a new product, after reviewing the results of the biological analysis and field evaluation after testing it on animals (cats) in cases of bacterial infections of the outer and middle ear, as it gave fruitful results in the work.