Formulation and Evaluation of a Povidone-Iodine Synergistic Spray Bandage

The integrity of the skin, the body's largest organ, is paramount for maintaining homeostasis and protecting against the external environment. When this barrier is breached due to injury, be it a minor abrasion, a burn, a surgical incision, or a chronic ulcer, the body becomes vulnerable to infection, fluid loss, and impaired thermoregulation. Effective wound management is therefore crucial not only for alleviating patient discomfort and preventing complications but also for facilitating timely and complete tissue repair. The history of wound care is as old as humanity itself, evolving from rudimentary applications of natural substances like leaves and honey to sophisticated modern dressings incorporating advanced materials and bioactive agents. The fundamental principles of wound management have remained consistent: cleansing the wound, preventing infection, maintaining an optimal moisture balance, and protecting the wound bed from further trauma. Traditional wound dressings, including woven and non-woven fabrics like gauze, adhesive tapes, bandages, and more advanced options such as hydrogels, hydrocolloids, alginates, and foams, have played a vital role in wound care for decades. Gauze, for instance, has been a mainstay for its absorbency and availability, often used to cover wounds and apply pressure. Adhesive bandages offer convenience for minor injuries, providing protection and immobilization. Hydrogels provide moisture to dry wounds, while hydrocolloids absorb exudate and create a moist environment conducive to healing. Alginates, derived from seaweed, are highly absorbent and useful for heavily exuding wounds. Foams offer cushioning and absorbency for various wound types. However, despite their widespread use, these traditional dressings are not without limitations. Frequent dressing changes can disrupt the delicate healing process, causing pain and potential damage to newly formed tissue . The removal of adhesive dressings can strip away epidermal layers, leading to "tape stripping" and delayed healing. Conforming these dressings to irregularly shaped wounds, such as burns or wounds around joints, can be challenging, often resulting in gaps or wrinkles that compromise protection and healing. Furthermore, the opacity of many traditional dressings necessitates their removal for wound assessment, increasing the risk of contamination and disturbing the wound bed. These limitations have driven significant innovation in the field of wound care, leading to the development of advanced wound dressings and novel application methods. Among these innovations, spray bandages have emerged as a promising technology, offering a unique approach to wound protection and management. Spray bandages are liquid formulations that, upon application to the skin, rapidly transform into a thin, flexible, and often transparent film. This film acts as a physical barrier, shielding the wound from bacteria, dirt, and other environmental contaminants. The ease of application, particularly for wounds in awkward locations or those with irregular contours, makes spray bandages a user-friendly option. . Moreover, the potential to incorporate therapeutic agents directly into the spray formulation allows for targeted delivery of drugs to the wound site, enhancing their efficacy and minimizing systemic side effects.

Types of Spray Bandages:

The diversity of spray bandage formulations stems from the wide range of film-forming polymers and active pharmaceutical ingredients (APIs) that can be employed. Understanding these components is crucial for tailoring spray bandages to specific wound types and treatment goals.

Based on Film-Forming Polymers:

1. Polyvinyl Alcohol (PVA) Based Spray Bandages: PVA is a water-soluble synthetic polymer known for its excellent film-forming properties, biocompatibility, and non-toxicity. PVA films are generally flexible and have good tensile strength. They can be easily dissolved in water or removed with specific solvents. PVA-based spray bandages are often favored for their ease of formulation and ability to incorporate hydrophilic drugs. The degree of polymerization and hydrolysis of PVA can be adjusted to fine-tune the film's properties, such as its water permeability and dissolution rate.
2. Cellulose Derivative Based Spray Bandages: Various cellulose derivatives, including ethyl cellulose, hydroxypropyl cellulose, and carboxymethyl cellulose, are used in spray bandage formulations. Ethyl cellulose, for example, is an ethyl ether of cellulose that forms hydrophobic films, offering good water resistance. These polymers often require organic solvents for dissolution and spraying. The properties of the resulting film can be modified by the type and concentration of the cellulose derivative, as well as the inclusion of plasticizers.
3. Acrylate Copolymer Based Spray Bandages: Acrylate copolymers, such as those based on ethyl acrylate and methyl methacrylate, are synthetic polymers that can form flexible and adherent films. These polymers are often dissolved in volatile organic solvents for spray application. The composition of the copolymer can be tailored to achieve specific film properties, including adhesion, permeability, and drug release characteristics. Acrylate-based spray bandages are known for their good adhesion to the skin and their ability to form durable films.
4. Silicone Based Spray Bandages: Silicones, such as dimethicone and silicone copolymers, are biocompatible polymers that form flexible and water-resistant films. Silicone spray bandages are often used for protecting skin and wounds from moisture and irritants. They are known for their breathability and non-irritating nature, making them suitable for sensitive skin. Silicone films can also provide a degree of elasticity, accommodating skin movement.
5. Polyurethane Based Spray Bandages: Polyurethanes are versatile polymers that can be formulated to create films with a range of properties, including flexibility, strength, and permeability. They can be formulated as solutions in organic solvents or as aqueous dispersions for spray application. Polyurethane spray bandages can offer good adhesion and durability, and their permeability can be controlled by the specific type of polyurethane used.
6. Natural Polymer Based Spray Bandages: Research is also exploring the use of natural polymers like chitosan, alginate, and collagen in spray bandage formulations. Chitosan, derived from chitin, has inherent antimicrobial and wound healing properties. Alginate, as mentioned earlier, is highly absorbent. Collagen provides a structural matrix that can promote cell growth. Formulating these natural polymers into sprays often requires specific processing techniques and may involve cross-linking to enhance film stability.

Based on Active Pharmaceutical Ingredients (APIs):

1. Antiseptic spray bandages: These are the most common type, incorporating agents like Povidone-Iodine, chlorhexidine, silver nanoparticles, or benzalkonium chloride to prevent microbial contamination of the wound. The choice of antiseptic depends on its spectrum of activity, safety profile, and compatibility with the film-forming polymer. This thesis focuses on a Povidone-Iodine spray bandage due to its broad-spectrum efficacy and well-established use in wound care.
2. Antibiotic spray bandages: Some spray bandages contain antibiotics, such as neomycin, bacitracin, or mupirocin, to treat or prevent bacterial infections. These formulations are typically used under medical supervision due to concerns about antibiotic resistance.
3. Wound healing promoting spray bandages: Emerging formulations incorporate growth factors (e.g., epidermal growth factor, platelet-derived growth factor), peptides, or other bioactive molecules aimed at accelerating the natural wound healing processes, such as angiogenesis, cell proliferation, and collagen synthesis.
4. Anesthetic spray bandages: These formulations contain local anesthetics like lidocaine or benzocaine to provide pain relief at the wound site. They are particularly useful for minor burns, abrasions, and insect bites.
5. Combination spray bandages: Some advanced spray bandages combine multiple apes, such as an antiseptic and a wound healing promoter, to address different aspects of wound management simultaneously.

The selection of the appropriate film-forming polymer and API is critical and depends on the specific application, the type and severity of the wound healing, the desired properties of the bandage (e.g., flexibility, adhesion, permeability), and the required therapeutic effect.

1.2 History of Spray Bandages:

The evolution of spray bandage technology is a testament to the ongoing quest for more effective and convenient wound care solutions. While the precise origins are difficult to pinpoint, the underlying concept of applying a protective liquid film to the skin has roots in early uses of natural resins and varnishes for wound sealing. Early formulations, emerging in the mid-20th century, primarily focused on creating a simple physical barrier. These "liquid bandages" often consisted of collodion (a solution of nitrocellulose in ether and alcohol) or similar film-forming substances. While effective in providing a protective layer, these early formulations often lacked flexibility, were prone to cracking, and could be irritating to the skin due to the solvents used. The advent of synthetic polymers in the latter half of the 20th century paved the way for more sophisticated spray bandage development. Polymers like polyvinyl alcohol (PVA), acrylate copolymers, and cellulose derivatives offered improved film properties, such as greater flexibility, better adhesion, and controlled permeability. Researchers began exploring the potential of these polymers for delivering therapeutic agents directly to the wound site. The inclusion of antiseptic agents marked a significant advancement. Povidone-Iodine, with its broad-spectrum antimicrobial activity and relatively low toxicity, became a popular choice for incorporation into spray bandage formulations. The convenience of applying an antiseptic directly to the wound in a protective film offered a significant advantage over traditional methods of wound cleansing and dressing. The late 20th and early 21st centuries witnessed further refinements in spray bandage technology. Innovations focused on:

• Improved Polymer Systems: Development of polymers with enhanced biocompatibility, flexibility, and durability.
• Solvent Optimization: Research into less irritating and faster-evaporating solvent systems.
• Enhanced Drug Delivery: Strategies to control the release of incorporated therapeutic agents, ensuring sustained and effective concentrations at the wound site. This included microencapsulation of the API within the polymer matrix.
• Propellant Technology: Advancements in aerosol propellants to ensure even and controlled application of the spray. Concerns about the environmental impact of chlorofluorocarbon (CFC) propellants led to the adoption of more eco-friendly alternatives like hydrocarbons and compressed gases.
• Specialized Formulations: Development of spray bandages tailored for specific wound types, such as burns (incorporating soothing and moisturizing agents) or surgical incisions (providing a sterile barrier).

The history of spray bandages reflects a continuous cycle of innovation driven by the need for improved wound care outcomes, enhanced patient comfort, and greater ease of use. The ongoing research and development in this field promise further advancements in the design and functionality of spray bandage products.

Advantages of Spray Bandages:

The growing popularity of spray bandages is underpinned by a multitude of advantages they offer over traditional wound dressings, addressing many of the limitations associated with conventional methods.

• Convenient Application: The spray format allows for effortless and contactless application of the bandage, a significant advantage, particularly for individuals with limited mobility or when dealing with wounds in difficult-to-reach areas such as the back, scalp, or between fingers and toes. The ease of application also reduces the potential for introducing contaminants to the wound during the dressing process, as direct physical contact is minimized. This is especially beneficial in field or emergency situations where sterile conditions may be challenging to maintain. Furthermore, for pediatric or elderly patients who may be anxious or uncomfortable with traditional dressing changes, the quick and relatively non-invasive application of a spray bandage can improve compliance and reduce distress.
• Conformability: Unlike pre-shaped traditional dressings, spray bandages form a liquid film that intimately contours to the exact shape and surface irregularities of the wound, regardless of its complexity. This ensures uniform coverage and protection, even for wounds around joints or on uneven surfaces where traditional dressings may wrinkle, bunch up, or leave gaps, compromising the barrier function and potentially leading to localized pressure points. The seamless nature of the sprayed film also minimizes the risk of edges lifting and exposing the wound to the environment.
• Transparency: Many spray bandage formulations dry to form a transparent or translucent film, allowing for direct visual monitoring of the wound bed without the need to remove the dressing. This is a significant advantage for healthcare professionals and patients alike, as it enables regular assessment of healing progress, detection of early signs of infection (such as increased redness, swelling, or purulent discharge), and evaluation of the need for further intervention without disturbing the wound and potentially disrupting the healing tissues. Reducing the frequency of dressing changes minimizes mechanical trauma to the wound and the surrounding skin, contributing to a more favorable healing environment.
• Reduced Risk of Secondary Trauma: Traditional adhesive dressings can adhere strongly to the wound bed, particularly if exudate dries and binds the dressing to newly formed granulation tissue.  Removal of such dressings can cause significant pain and damage to these fragile tissues, potentially delaying healing and increasing the risk of scarring. Spray bandages, especially those formulated with appropriate polymers and plasticizers, typically form a thin, flexible film that adheres gently to the surrounding intact skin but has minimal adhesion to the wound bed itself. This reduces the likelihood of secondary trauma upon natural sloughing of the film or when removal is necessary, promoting a less disruptive healing process.
• Breathability: The concept of optimal wound healing has evolved over time, with the understanding that maintaining a moist wound environment while allowing for adequate gas exchange is crucial. Some spray bandage formulations are designed to be semi-permeable, allowing for the passage of oxygen and water vapor while preventing the entry of bacteria and other contaminants. This breathability helps to prevent excessive moisture accumulation, which can lead to maceration of the surrounding skin, and supports the metabolic needs of the healing tissues. The permeability characteristics of a spray bandage are largely determined by the type and concentration of the polymer used, as well as the presence of any additives.
• Drug Delivery: One of the most significant advantages of spray bandages is their potential to act as a vehicle for delivering therapeutic agents directly to the wound site. By incorporating antiseptics like Povidone-Iodine, antibiotics, growth factors, or other wound healing promoters into the liquid formulation, the spray bandage can provide a sustained and localized release of these drugs, maximizing their efficacy at the target site while minimizing systemic absorption and potential side effects. The uniform application of the spray ensures even distribution of the drug across the wound surface. Furthermore, the film formed can act as a reservoir, controlling the rate and duration of drug release, which can be tailored by adjusting the polymer matrix and the formulation process.
• Patient Compliance: The ease of application, the transparency allowing for discreet monitoring, and the reduced pain associated with dressing changes can significantly improve patient compliance with the prescribed wound care regimen. This is particularly important for patients managing chronic wounds at home or for active individuals who require a dressing that does not restrict movement or draw undue attention. The quick application process also makes spray bandages a convenient option for busy individuals.

Disadvantages of Spray Bandages:

Despite their numerous advantages, spray bandages also have certain limitations that need to be considered when determining their suitability for a particular wound.

• Limited Absorption: Most spray bandages form a thin, non-absorbent film designed to protect the wound. As such, they are generally not suitable for heavily exuding wounds, where the primary need is to manage large amounts of drainage. Applying a spray bandage to a highly exudative wound may trap the exudate beneath the film, potentially leading to maceration of the surrounding skin and hindering the healing process. In such cases, more absorbent dressings like alginates, foams, or hydrocolloids would be more appropriate for managing the exudate before a spray bandage could potentially be used in the later stages of healing when exudate levels have decreased.
• Potential for Irritation: The formulation of spray bandages typically involves polymers dissolved in volatile solvents, such as alcohols and acetone. While these solvents are necessary for achieving a sprayable consistency and rapid drying, they can potentially cause skin irritation, dryness, or allergic reactions in some individuals, particularly those with sensitive skin or pre-existing skin conditions. The choice of polymer and any additives, such as plasticizers or fragrances, can also contribute to irritation in susceptible individuals. Thorough biocompatibility testing is therefore crucial during the development of spray bandage formulations.
• Durability: The thin film formed by a spray bandage, while flexible, may not always be as durable as some traditional dressings, particularly in areas subject to significant friction or movement, such as joints or areas that are frequently rubbed by clothing. Physical stress can lead to cracking, peeling, or detachment of the film, compromising the protective barrier and potentially requiring more frequent reapplication. The durability of the film is influenced by the type and concentration of the polymer, the presence of plasticizers, and the thickness of the applied layer, which can be affected by the application technique.
• Application Technique: The effectiveness of a spray bandage relies heavily on proper application technique. Inadequate spraying, such as holding the nozzle too close or too far from the wound, or applying an insufficient amount of the solution, can result in a thin, uneven, or incomplete film with gaps that do not provide adequate protection. Patient education and clear instructions for use are therefore essential to ensure proper application and optimal performance of the spray bandage. Factors such as the viscosity of the solution and the design of the spray nozzle also play a role in achieving a uniform and effective film.
• Cost: Some advanced spray bandage formulations, particularly those incorporating novel polymers or bioactive agents, may be more expensive than traditional wound dressings like gauze or standard adhesive bandages. The cost-effectiveness of spray bandages needs to be considered in the context of their potential benefits, such as reduced dressing change frequency, improved healing outcomes, and enhanced patient comfort. However, for routine management of minor wounds, the higher cost of some spray bandages may be a limiting factor for some patients or healthcare systems

2.1 Review of Literature

The use of topical antiseptic formulations has gained significant attention in modern wound care management due to their ease of application, effectiveness in infection control, and promotion of wound healing. Among various antiseptics, Povidone-Iodine (PVP-I) is a widely recognized broad-spectrum antimicrobial agent. It has been extensively used in various forms such as solutions, ointments, and powders for the treatment of minor wounds, cuts, burns, and infections.

1. Povidone-Iodine as a Topical Antiseptic

Povidone-Iodine is a stable chemical complex of polyvinylpyrrolidone (PVP) and elemental iodine. It slowly releases free iodine in aqueous solution, which acts as the active antimicrobial moiety. Its effectiveness spans bacteria, viruses, fungi, protozoa, and spores, making it ideal for inclusion in wound management formulations. Studies have shown that PVP-I is capable of maintaining its antimicrobial activity in the presence of organic matter, unlike some other antiseptics. Furthermore, it is less cytotoxic to human tissues compared to tincture iodine or hydrogen peroxide when used at appropriate concentrations, especially in a 10% aqueous formulation.

2. Spray Bandage Technology

Spray-on bandages are film-forming liquid formulations that form a transparent, flexible, and breathable protective layer on the skin upon application. They are particularly useful in covering irregular wound surfaces and minimizing contamination. The film not only protects the wound from external pathogens but also facilitates oxygen exchange, which is essential for optimal wound healing. The film-forming agent used in this formulation is polyvinyl alcohol (PVA), a synthetic polymer known for its biocompatibility, water solubility, and excellent film-forming ability. PVA contributes to the mechanical strength and flexibility of the film, making it suitable for use on mobile or joint areas.

3. Role of Plasticizers and Solvents

Incorporation of plasticizers like glycerin and propylene glycol enhances the flexibility and comfort of the film, preventing it from becoming brittle and improving its adhesion to the skin. These compounds also exhibit mild humectant properties, maintaining hydration at the wound site. Volatile solvents such as isopropyl alcohol and acetone (or ethanol) are critical for quick drying and spreading of the formulation. They help the film set within seconds, providing an almost instant protective barrier after application. Moreover, isopropyl alcohol serves a dual purpose by contributing to the antimicrobial profile of the formulation.

4.Antimicrobial Synergy and Additional Components

Optional additives such as hydrogen peroxide provide synergistic antimicrobial effects when combined with Povidone-Iodine, although care must be taken to ensure chemical compatibility. Some studies suggest a combination can broaden the antimicrobial spectrum and enhance wound debridement. Fragrance agents and pH adjustment agents (citric acid or sodium hydroxide) are commonly included in cosmetic pharmaceutical preparations to enhance user experience and skin compatibility. The skin’s natural pH lies between 4.5–6.5; hence, formulations should ideally maintain a neutral to slightly acidic pH to avoid irritation.

5. Evaluation and Quality Parameters

Standard pharmaceutical tests such as visual inspection, pH determination, viscosity testing, and drying time analysis are essential for ensuring formulation quality and usability. More advanced methods such as zone of inhibition assays are employed to test antimicrobial efficacy, particularly against common skin pathogens like Staphylococcus aureus and Escherichia coli. Moreover, skin irritation and stability tests are crucial for ensuring the safety and long-term effectiveness of the product. According to dermatological standards, a well-formulated spray bandage should not induce redness, burning, or allergic reactions, and should maintain its chemical an physical properties over time.

3.1. MATERIAL AND METHOD

Drug Profile: Povidone-Iodine

• Synonym: PVP-Iodine, Polyvidone-Iodine  
• Empirical Formula: (C6H9NO)n·xI
• Chemical Name: Poly(1-vinyl-2-pyrrolidinone)-iodine complex
• Boiling Point: Decomposes before boiling
• Melting Point: Decomposes around 300 °C

Mechanism of Action: Povidone-Iodine is a broad-spectrum antiseptic that works by the gradual release of free iodine. The free iodine penetrates microbial cells, oxidizing essential cytoplasmic and membrane components, including proteins and nucleic acids. This non-selective mechanism of action makes it effective against a wide range of bacteria, viruses, fungi, and protozoa. The povidone acts as a carrier, solubilizing the iodine and providing a sustained release, reducing its irritancy compared to tincture of iodine.  

3.2 Materials:

• Polyvinyl Alcohol (PVA)
• Distilled Water
• Glycerin
• Propylene Glycol
• Isopropyl Alcohol
• Acetone (or Ethanol)
• Povidone-Iodine 10% solution
• Hydrogen Peroxide 3% solution (optional)
• Fragrance Oil (optional)
• Citric Acid
• Sodium Hydroxide
• pH strips or pH meter
• Viscometer
• Sterilized spray bottles
• Petri dishes
• Sterile swabs
• Glass plates or synthetic skin material
• Fabric or synthetic skin material for adhesion testing
• Animal model for skin irritation test (if applicable and ethically approved)
• Storage containers for stability testing

Method:

The procedure outlined in the initial prompt will be followed with careful attention to detail and accurate measurements. Briefly:

1. Preparation of PVA Solution: Dissolve PVA in heated distilled water with continuous stirring.
2. Incorporating Glycerin and Propylene Glycol: Add plasticizers to the PVA solution and mix.
3. Adding Solvents: Incorporate isopropyl alcohol and acetone (or ethanol) and stir well.
4. Incorporating Povidone-Iodine: Gently mix in the Povidone-Iodine solution.
5. Adding Hydrogen Peroxide (Optional): If desired, add and mix gently.
6. Adding Fragrance (Optional): If desired, add and mix thoroughly.
7. Adjusting Volume and Mixing: Add remaining distilled water to reach the final volume and mix.
8. Final Adjustment (Optional for Consistency and pH): Adjust consistency and pH if necessary.
9. Packaging: Transfer the solution into sterilized spray bottles.

4.1. Aim and Objectives

Aim:

To formulate and comprehensively evaluate a Povidone-Iodine spray bandage with optimal film-forming properties, antimicrobial efficacy, and biocompatibility for effective wound healing.

Objectives:

1. To develop a suitable formulation for a spray bandage using polyvinyl alcohol as the film-forming polymer and incorporating Povidone-Iodine as the antiseptic agent.
2. To optimize the concentrations of plasticizers (glycerin and propylene glycol) and solvents (isopropyl alcohol and acetone/ethanol) to achieve a flexible, fast-drying, and well-adhering film.
3. To prepare the formulated solution and package it into spray bottles.
4. To evaluate the physical properties of the spray bandage, including visual appearance, pH, viscosity, and drying time.
5. To assess the adhesion properties of the formed film.
6. To determine the in vitro antimicrobial efficacy of the Povidone-Iodine spray bandage against selected skin pathogens (e.g., Staphylococcus aureus and Escherichia coli) using the zone of inhibition method.
7. To conduct a preliminary assessment of the biocompatibility of the spray bandage through a skin irritation test on a suitable model.
8. To evaluate the stability of the formulated spray bandage under different storage conditions.

I. Materials and Ingredients

Table No. 4.1.1 . Spray Bandage Formulation Ingredient

II. Equipment Required

• Beakers (preferably glass, 100 ml+ capacity)
• Magnetic stirrer or glass stirring rod
• Measuring cylinders and pipettes
• Weighing balance
• Water bath or heating plate with temperature control
• pH meter or pH test strips
• Viscosity meter
• Sterilized spray bottles (preferably amber glass or plastic)
• Funnel, gloves, lab apron, goggles

III. Detailed Procedure

Step 1: Preparation of PVA Solution

Purpose: To create a base film-forming solution.

1. Weigh 5 g of PVA and transfer into a clean, dry beaker.
2. Measure 18 ml of distilled water.
3. Heat the water gently to 40–50°C in a water bath or on a hot plate.
4. Slowly add PVA to the warm water while continuously stirring to avoid clumping.
5. Continue stirring until a clear, lump-free, viscous solution is obtained.
6. Allow to cool to room temperature.

Fig. 4.1.1 Preparation of PVA Solution using Water Bath

Note: Heating beyond 60°C may degrade PVA or reduce its film strength.

Step 2: Incorporation of Plasticizers

Purpose: To enhance flexibility, prevent brittleness of the film.

1. Measure 2 ml of glycerin and 1 ml of propylene glycol.
2. Add both to the cooled PVA solution.
3. Stir well until uniformly mixed.

Step 3: Addition of Solvents

Purpose: To enhance drying speed and improve sprayability.

1. Measure 35 ml of isopropyl alcohol and 40 ml of acetone (or ethanol).
2. Gradually add the solvents to the existing PVA-plasticizer mix while stirring.
3. Ensure complete homogenization to prevent phase separation

Caution: Work in a well-ventilated area or under a fume hood due to solvent volatility.

Fig 4.1.2 Addition of Solvent to PVA-Plasticizer Mix

Step 4: Incorporation of Povidone-Iodine

Purpose: To introduce the main antiseptic agent.

1. Measure 10 ml of 10% Povidone-Iodine solution.
2. Slowly pour into the well-mixed solvent base.
3. Stir gently to ensure uniform dispersion and prevent foaming.

Tip: Avoid vigorous shaking to reduce oxidative degradation of iodine.

Step 5: Add Hydrogen Peroxide

Purpose: To enhance antimicrobial effectiveness.

1. If desired, add 3 ml of 3% hydrogen peroxide.
2. Stir gently and monitor for effervescence or pH changes.

Note: Excess hydrogen peroxide may destabilize iodine; test stability over time.

Step 6: Optional – Add Fragrance

Purpose: To improve user experience.

1. Add 0.1 ml (2–3 drops) of cosmetic-grade fragrance oil.
2. Mix thoroughly. Avoid overpowering scents that may irritate wounds.

Step 7: Final Volume Adjustment

Purpose: To standardize the total volume to 100 ml.

1. Top up the mixture with approximately 18 ml of distilled water to reach 100 ml total volume.
2. Stir well to ensure a uniform and homogenous mixture.

Fig 4.1.3 Final Volume Adjustment to 100ml

Step 8: pH Adjustment (Optional)

Purpose: To ensure skin compatibility (ideal pH: 5.0–7.0)

1. Check the pH using pH strips or a calibrated pH meter.

1. Adjust if necessary:
   1. Add citric acid solution dropwise to lower pH.
   2. Add dilute sodium hydroxide solution to raise pH.
2. Stir and re-check until desired pH is achieved.

Target pH: 5.5–6.5 is optimal for skin tolerance and antimicrobial efficacy.

Step 9: Packaging

Purpose: To store and apply the product safely.

1. Pour the final solution into a sterilized spray bottle using a funnel.
2. Seal the bottle tightly.
3. Label with contents, date of manufacture, and storage instructions
4. Shake gently before each use.

Fig. 4.1.4 Packing of Formulation

Fig. 4.1.5 Final labelling of spray bandage

Storage Recommendation: Store in a cool, dark place away from direct sunlight to preserve iodine potency.

IV. Evaluation and Quality Control Tests

The evaluation tests described in the initial prompt will be conducted as follows:

1. Visual Inspection: Observe the prepared solution for color, clarity, consistency, and the presence of any particulate matter.
2. pH Test: Determine the pH of the final solution using calibrated pH strips or a pH meter. Measurements will be taken in triplicate.
3. Viscosity Test: Measure the viscosity of the solution using a suitable viscometer at a controlled temperature. Measurements will be taken in triplicate.

Fig 4.1.6 Viscosity Measurement using an Ostwald Viscometer

4. Drying Time: Spray a known amount of the solution onto a clean glass plate or synthetic skin material and record the time taken for the film to become tack-free and dry to the touch. The average of three measurements will be recorded.
5. Adhesion Test: Spray the solution onto a piece of fabric or synthetic skin material and allow it to dry. Assess the ease of removal and the degree of adhesion by gently attempting to peel off the film. A qualitative assessment will be made (e.g., slight, moderate, strong adhesion).
6. Antimicrobial Efficacy Test (Zone of Inhibition): Prepare nutrient agar plates seeded with standardized cultures of Staphylococcus aureus and Escherichia coli. Apply a known amount of the spray bandage solution to sterile filter paper discs placed on the agar surface. Incubate the plates at 37°C for 24 hours and measure the diameter of the zone of inhibition around each disc. A control disc with Povidone-Iodine solution of known concentration will also be included. Experiments will be conducted in triplicate.
7. Skin Irritation Test: (This will be conducted according to ethical guidelines and using an appropriate model, if feasible. A detailed protocol will be established outlining the application method, duration, and observation period for signs of irritation such as redness, swelling, or itching.) Alternatively, in vitro biocompatibility assays may be considered.
8. Stability Test: Samples of the spray bandage will be stored under different conditions (e.g., room temperature, 4°C, elevated temperature, light exposure) for a predetermined period (e.g., 1, 2, and 3 months). At regular intervals, the samples will be visually inspected, and tests for pH, viscosity, and antimicrobial efficacy will be repeated to assess any changes in the product's properties over time.

Table No. 4.1.2Evaluation of Antimicrobial Spray Properties