A Review Article on Formulation and Evaluation of Antibacterial and Antiprotozoal Powder of Satranidazole

Abstract

The aim of the paper was to develop Satranidazole-containing Antibacterial and antiprotozoal Powder to Treat Various Bacterial and protozoal infections. Drugs from nitroimidazole category are generally bitter in taste. Oral formulation with bitter taste is not palatable. Geriatrics and paediatrics patients usually suffer from swallowing difficulties. Many other patients in some disease conditions avoid swallowing tablets. Satranidazole is a new nitro-imidazole derivative with bitter taste and is available in market as film coated tablet. Satranidazole is a class II drug per biopharmaceutical classification systems with poor aqueous solubility. It is highly effective, well accepted and clinically useful against protozoa. It is two times more active than other nitroimidazole against amoebiasis and giardiasis. It is also more active against anaerobes than other nitrogen containing imidazole’s. Some drugs are available for the chemoprophylaxis and treatment of all the major protozoal diseases of man. However, such drugs are not always active by the oral route, efficacy is sometimes limited, toxicity can be severe and drug resistance is an increasing problem.

Keywords

Introduction

Satranidazole is under the class of BCS class II, used in the treatment of protozoal infection (Entamoeba histolytica, Tenia vaginalis, Giardia), antibiotics, amoebicidal, and shows activity in the treatment of inflammatory bowel diseases subdivided as ulcerative colitis and Crohn’s disease. Satranidazole is convenient   to   show   activity   towards   colonic   bacteria   and protozoal diseases with higher plasma absorption with high residence time than marketed drugs to treat colonic disorders 5. Satranidazole   is   also   recommended   for   infections   that occurred after surgery and infections involved in the liver, brain, heart caused by microorganisms.  Satranidazole makes different from other marketed drugs to treat colon diseases as it has high physicochemical stability, high therapeutic efficacy, feasible analytical   methods   available   to   develop a  proper dosage form, and low adverse effects with fewer adverse events.  Satranidazole is active against parasites by damaging their DNA or any genetic materials to deactivate their activity without causing cell damages.  In the treatment of periodontal treatment, Satranidazole plays an important role to reduce inflammation. Nitro-heterocyclic compounds have a wide variety of applications, ranging from food preservatives to antibiotics. Nitroimidazoles have therapeutic uses as anaerobic antibacterials and antiprotozoal agents. 5-nitroimidazoles are a well-established group of antiprotozoal and antibacterial agents. The antimicrobial activity of these chemotherapeutic agents inhibits the growth of both anaerobic bacteria and certain anaerobic protozoa such as Trichomonas vaginalis, Entamoeba histolytica and Giardia lamblia. They have other interesting biological activities of therapeutic potential such as, radiosensitizers in treatment of cancer, control of fertility, and antitubercular therapy. Satranidazole is a novel 5-nitromidazole derivative. It is a light lemon-yellow crystal and slightly hygroscopic in nature. It is not official in any of the pharmacopoeia. It is more active towards anaerobes than many 5 nitroimidazoles because its relatively high redox potential may make it more resistant to inactivation by oxygen. It shows activity against E. histolytic and Giardia. Chemically, it a first derivative which combines nitroimidazole and imidazolidinone rings in their structure. It possesses C-N linkage at second position of imidazole ring. Protozoal infections are common amongst the people in undeveloped tropical and subtropical countries, where sanitary con dictions, hygienic practices and control of vectors of transmission are insufficient. Satranidazole is an antiprotozoal and anti-bacterial drug belonging to nitroimidazole derivatives and was selected as a drug of choice because it is very potent, well tolerated and clinically effective against common protozoa.1,4 Satranidazole is a systemically acting drug which is twice as effective as other nitroimidazoles. It is successfully used in the treatment of some parasitic diseases (intestinal and hepatic amoebiasis, giardiasis, trichomoniasis and anaerobic infections). But it exhibits a low bioavailability which is related to its poor aqueous solubility. Satranidazole falls under class II compounds as per biopharmaceutical classification system. It is used in the treatment of intestinal and hepatic amoebiasis, giardiasis, trichomoniasis, and anaerobic infections. Its dose is 300 mg twice daily for 3–5 days in the treatment of amoebiasis and 600 mg as a single dose in the treatment of giardiasis and trichomoniasis. It is reported that Satranidazole exhibits significantly higher plasma concentrations than metronidazole and has a plasma elimination half-life of 1.01 hour which is significantly shorter than the corresponding metronidazole half-life of 3.62 hour. Also, Satranidazole is having better tolerability, absence of neurological, and disulfiram-like reactions and it can be preferred in patients with susceptible neurological symptoms.

DRUG PROFILE: -

 Name:  Satranidazole [Spanish], Satranidazolum [Latin].

Structure:

• IUPAC name: 1-(1-Methyl-5-nitro-1H-imidazol-2-yl)-3-(methylsulfonyl)-2-imidazolidinone
• Molecular formula:  C8H11N5O5S
• Category:  Antiamoebic and Antiprotozoal
• Molecular weight:  289.26844 [g/mol]
• Solubility: Insoluble in water, soluble in dioxane and dimethyl formamide (DMF).

• Description: A yellowish, crystalline powder and slightly hygroscopic in nature
• Storage: Store in a room temperature away from light
• Standards: Satranidazole contains not < 99.67 percent.
• Half-life: Plasma elimination half-life of 1.01 hr
• Dose: 300 mg -600mg
• Uses: Satranidazole commonly used in amoebic liver abscess, Trichomoniasis, Giardiasis.
• Adverse effects: Headaches, palpitations, high blood pressure, hot flushes, weakness, dizziness, nervousness, dry mouth, change in taste
• Over dosage: High doses for prolonged periods are carcinogenic.

MECHANISM OF ACTION: -

As per other nitroimidazoles, Satranidazole also act on the nucleic material of the cell. It has been observed that during reduction, its ability to break DNA. Substantial breakdown to DNA was measured by viscometry. The satranidazole produces extensive DNA breakage characterized by strand breakage and helix destabilization. Its comparison with other 2 and 5-nitroimidazoles indicate it may be more potent towards anaerobes other 5-nitroimidazoles because its high redox potential is more resistant to inactivation by oxygen. It is recently introduced as an anti-protozoal agent in tablet dosage form. It is a highly potent, well tolerated, and clinically useful agent against common protozoa. It is rapidly absorbed and exhibits higher plasma and liver concentration than metronidazole.

EVALUATION PARAMETERS STUDIED FOR POWDER-

1) Bulk and Tapped density.

Bulk density measurement carried out by using flat- round measuring cylinder with a volume of 250ml. The measuring cylinder was half filled with the 5gm of the powder and the reading was observed to the nearest milliliter.

2) Angle of repose

It was determined by fixed funnel method onto a bottom graph paper. The funnel was fixed on a height, and moved according to the height of the conical heap in order to keep a constant distance between the top of the heap and the funnel. The angle of repose was determined by measuring the height of the cone of powder with the help of the formula. Angle of repose = tan-1(h/r)

3) Hausner’s ratio

Flow property was defined according to the Hausner ratio Hausner ratio = (Tapped density)/ (Bulk density) Flow of powder was measured using a standard funnel. In a dry funnel, whose bottom opening has been blocked, the sample was introduced without compacting. After removing the blockage from the bottom opening of the funnel, the time taken for the entire sample to flow out thought the funnel was measured. Hausner ratio = (tapped density / bulk density)

4) Moisture content test or hygroscopic

The hygroscopic nature can be analyzed by putting the formulation in open environment at room temperature after weighing it. After sometime place it in a hot air oven and observe the weight loss by weighing it after some time.

5) Skin irritancy test:

The formulation was applied on the human skin.

 6) Stability test

The powder was packed in a container and was stored at room temperature. After 1 month the powder was checked for its organoleptic property.

NEED OF RESEARCH/ FUTURE SCOPE: -

Drugs from nitroimidazole category are generally bitter in taste. Oral formulation with bitter taste is not palatable. Geriatrics and paediatrics patients usually suffer from swallowing difficulties. Many other patients in some disease conditions avoid swallowing tablets.

Satranidazole is a new nitro-imidazole derivative with bitter taste and is available in market as film coated tablet.

The purpose of this research was to mask the bitter taste of Satranidazole by Formulating Powder and to Treat various Protozoal and Bacterial infection.

CONCLUSION:

Topical treatment of the Bacterial and Protozoal infections has been preferred due to its advantages over oral treatment such as inhibition of systemic first-pass metabolism, targeting of the drug on the site of infection. On the other hand, appropriate drug concentrations in target site of the skin should be provided to ensure the effective topical treatment. In this context, formulation of topical Antibacterial and Antiprotozoal dosage form plays a key role for inhibition of the Protozoal infection by showing direct action on the skin.

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