Self-Bubbling Hydrogel for Uti: A Novel Solution with Amoxicillin and Corn Silk

Urinary Tract Infection: UTI is defined as microbial pathogens in urinary tract. A urinary tract infection is one of the most common bacterial infections in woman. It is mainly caused by anatomy, sexual activity, short urethra, behavioral factor.

The infection of bladder and urethra are referred to as infection of lower urinary tract, whereas is kidney and ureter infection is as indication of upper urinary tract infection.

• Numerous pathogens, including both Gram-positive and Gram-negative bacteria and fungi, can cause urinary tract infections (UTIs). Women, children, and elderly patients who are otherwise healthy are usually the ones that suffer from simple UTIs. 
• Indwelling catheters, anomalies of the urinary system, immunosuppression, or antibiotic exposure are typically linked to complicated UTIs.  Uropathogenic Escherichia coli (UPEC) is the most frequent cause of both simple and complex UTIs.  Klebsiella pneumoniae.
• Staphylococcus saprophyticus, Enterococcus faecalis, group B streptococcus (GBS), Proteus mirabilis, Pseudomonas aeruginosa, Staphylococcus aureus, and Candida spp. Are additional causal agents for uncomplicated UTIs, in order of prevalence. 
• The other causal agents for complicated UTIs are Enterococcus species, K. pneumoniae, Candida species, S. aureus, P. mirabilis, P. aeruginosa, and GBS, in order of prevalence.

Types of Urinary Tract Infection:

• Urethritis: It is an infection to urethra and usually represents with painful urination.
• Cystitis: It is an infection to bladder and usually represents with abdominal pain, fever and blood in urine.
• Pyelonephritis: It is a serious type of infection which involves infection to kidney and it usually represents with backache, nausea, vomiting, pus forming in kidney.

UTI is mostly caused by bacteria E.coli , Klebsiella pneumonia ,staphylococcus faecalis.

• Signs of urinary tract infection:

• Pain in flank , abdomen, pelvic area
• Pressure in lower part of your pelvis
• Foul smelling pee
• Frequent urination
• Pain when you pee
• Blood in pee

Why Hydrogels?

You can see there are various dosage form available in market to treat UTI but we choose to form a floating hydrogel due to various Properties like:

Prolonged Residence Time: Floating hydrogel can remain in urinary tract for longer Period of time, allowing for sustained release of antibiotic.

Target Delivery: It can be designed to target specific area tract of Urinary tract reducing its side effects.

Effective against biofilms: Floating hydrogel can effectively target & eradicate biofilms which  are common cause of UTI

Enhance Bioavailability: Floating hydrogel can enhance the bioavailability of antibiotic, allowing the lower doses.

Floating Hydrogel

• Hydrogel had been used as drug reservoir to extend the drug residence time in bladder. Due to the high viscosity of hydrogel serious problems are
• Urinary obstruction due to gel adherence
• Bladder irritation symptoms, such as blood clots in bladder.

This hydrogel, made of PEG and ammonium bicarbonate, stays liquid when cool but turns into a gel at body temperature. It forms bubbles that help it float in urine, preventing blockage and allowing slow, controlled drug release

• Intravesical instillation of drug solutions results into the elimination of drug solution from bladder after the first voiding of urine.
• To solve this problem floating hydrogel with self-generating micro- bubbles as a new delivery system very helpful for UTI.
• It floated in urine, avoiding the urinary obstruction and bladder irritation that ordinary hydrogels caused.

Characteristics:

1. Buoyancy:  Floats on gastric (stomach) fluid
2. Controlled Drug Release: Releases medicine slowly over time
3. Stability in Acidic Conditions: Remains stable in stomach acid (low pH)
4. Lightweight Structure: Made with air pockets or low-density materials
5. Long Gastric Retention Time: Improves effectiveness of drugs meant for stomach absorption
6. Bioadhesiveness: Some types can gently stick to the stomach wall

Aim And Objective

Aim: To formulate floating hydrogel with self generating micro bubbles for treatment of UTI.

• Combination of synthetic and herbal drug (Amoxicillin trihydrate and corn silk) will give the better effect.
• Initially, Formulation will be in liquid form, when injected in body(ie.37) it gets converted into gel form
• Due to presence of ammonium bicarbonate (NH4HCO3) it forms microbubbles and flots on urine which leads to adhession  to the mucosa of urinary bladder.
• As the E-coli bacteria colonice on the mucosa of urinary bladder,the drug acts on it and  inhibit the cell wall synthesis in the bacteria.

Rationale And Need

• Floating hydrogel is novel drug delivery system which is site specific drug delivery system.
• It will work as localized drug delivery system over systemic drug delivery.
• This formulation will give sustained release of drug in urinary bladder, which help to reduce the frequent dosing.
• To overcome the disadvantage of other formulation for UTI the floating hydrogel was prepared.
• Formulation will be introduced to patient by means of catheter, It is suitable dosage form for bed ridden patients, in case of complicated UTI.

Justification of Drug and Excipient Drug:

• Amoxicillin is an antibiotics used for treatment of bacterial infection.
• Highly soluble in water (hydrophilic) hence it is best choice for the preparation of hydrogel.
• MOA: It inhibit the cell wall synthesis, hence it helps to reduce the E.coli concentration.

• Herbal Drug:

• Corn silk extract obtained from the corn that is collected from Zea maize
• It is used in treatment of UTI
• It shows anti-inflammatory effect

• Polyethylene Glycol (PEG 400) – Humectant, Temperature sensitive gelation.
• Carbopol 934 - Gelling agent, Thickening agent.
• Ammonium Bicarbonate - Bubble forming agent.

Preformulation Studies

Evaluation Tests

• Characterization of corn silk solution
• Melting and Determination of solubility
• UV Spectroscopy of drug
• MIC (Minimum Inhibitory Concentration)
• pH and Viscosity
• Effects of different pH

Characterization of Corn silk Solution:

By the visual appearance these observations were noted

? Determination of Solubility:

Solubility of corn silk powder was tested in distilled water, ethanol, methanol, acetone.

• 1 gm of powder weighed accurately and dissolved in 10 ml solution. The solubility of Corn silk powder found in water.
• The corn silk powder solubility was checked in other solvent & the solubility observed were as

Melting point and Solubility of Drug

• Melting Point

Melting point of amoxicillin trihydrate was determined by the open capillary method.

The melting point noted was 192?C-194?C.

• Solubility:

Solubility of the drug was determined with the help of various solvents i.e distilled water, ethanol, methanol, acetone.

1 mg of drug weighed accurately and dissolved in 10 ml of various solvents

Solubility of drug found in water. In other solvents like ethanol, methanol, acetone it gave poor solubility.

UV

UV Spectroscopy

Amoxicillin trihydrate was analyzed by using UV at 226 nm.

Here 6.8 phosphate buffer was used for analysis of drug. R² was found to be 0.9932.

MIC

Here 5.6 gm of nutrient agar was added in 200ml of water and nutrient agar solution was prepared. The solution was sterilized in the autoclave for 45 min.

The nutrient agar solution was poured in the Petri plate, the plate was inoculated with E.coli. Plates were cooled, and then with help of borer well was formed in the plate.

Here 0.2 ml of drug solution of different concentration were poured in well i.e 40mg, 80mg, 120mg, 160mg, 200mg respectively.

The plates were incubated in the incubator for 24 hr Zone of inhibition was observed and recorded.

Evaluation

pH and Viscosity

pH

F1 batch showed 6.8 pH which was similar with the urine.

Viscosity

The formulation should have an optimum viscosity that allows the ease of administration as liquid and produce satisfactory gel strength.

Viscosity was determined with the help of Brookfield viscometer. here spindle no 64 was used to check the viscosity.

The viscosity of formulation are given in between 3120-3370 centipoise.

F1 batch shown the an optimum viscosity than other batches i.e 3370 centipoise.

Bubble Size

Bubble size was determined with the help of optical microscope.

Bubble size determination is important factor for the formulation because as the bubble size decrease it increase the foam ability of the formulation and also it is responsible to increase the resident time.

Bubble size was determined with the help of optical microscope. Bubble size of the particle should be in the range of 20µm – 400µm

(1)

(2)

Effect of different pH on floating hydrogel

The 5ml of floating hydrogel was added in 200 ml of different pH solutions i.e 6,8,9

Here it showed that in any pH condition floating hydrogel float on solution. As shown in fig.

Plant Profile

• Plant : Corn Silk
• Kingdom: Plantae
• Family : Poaceae
• Genus : Zea
• Species : Mays
• Binomial name: Zea maize
• Uses: bladder infection, UTI, CHF, high blood Pressure
• Phytochemical constituents: proteins, potassium, resins, maizenic acid, fixed oil (oleum maydis)

Formulation Method (Floating   Hydrogel)

Here 4ml of PEG was added in distilled water and then 0.5g of ammonium bicarbonate & 0.5g of Carbopol 934 was weighed accurately

Add Amoxicillin was weighed accurately i.e. 200 mg & mixed in the above solution & stirred it, till it homogenizes.

In the above solution 1 ml corn silk solution was added & mixed it properly & stored it.

Simulated   Urine

This ready-to-use solution has the same composition as Artificial Human Urine and closely resembles human urine.

Simulated Urine

• Simulated urine (also called synthetic urine or artificial urine) is a laboratory-made liquid designed to closely mimic the chemical composition, appearance, and sometimes even the smell of real human urine.
• It typically contains: Water, Urea, Creatinine Salts (like sodium, potassium, and chloride) Sometimes uric acid or other compounds found in natural urine.

What Is Catheter?

•  A Catheter is a thin, flexible tube that is inserted into body to remove urine blood or other fluids from body.
• It is also used to deliver medication and nutrients or other substances directly into the body.

Types Of Catheters:

1. Direct access to the bladder
2. Localized treatment
3. Minimizing systemic absorption
4. Reducing risk of complication
5. Improve efficacy & Enhanced safety
6. Ease of insertion

Storage Conditions

Hydrogels should be kept in a temperature-controlled environment, ideally between 5°C to 27°C (41°F to 81°F) and in their original shipping plastic bag. For long-term storage, dry conditions may be preferred, while maintaining moisture can be achieved by storing in a sealed container in the refrigerator.