A Comprehensive Monograph on Povidone (Polyvinylpyrrolidone): From Pharmaceutical Excipient to Antiseptic Carrier

Executive Summary

Povidone, a synthetic polymer known chemically as polyvinylpyrrolidone (PVP), stands as a substance of remarkable versatility in the medical and pharmaceutical fields.[1] This report provides a comprehensive analysis of Povidone, examining its dual identity as both a fundamental pharmaceutical excipient and a critical component of a widely used antiseptic.

First, Povidone is a ubiquitous and multi-functional excipient, valued for its exceptional safety profile in oral formulations, biocompatibility, and unique solubility in both aqueous and oil-based solvents. These properties allow it to serve numerous roles in drug manufacturing, most notably as a binder to ensure tablet integrity, a disintegrant to promote drug release, and a solubilizer to enhance the bioavailability of poorly soluble active ingredients.[4]

Second, Povidone functions as the carrier polymer in the Povidone-Iodine complex, an iodophor that revolutionized antiseptic practice. By forming a stable complex with elemental iodine, Povidone facilitates a sustained release of the microbicidal agent, thereby retaining iodine's potent, broad-spectrum efficacy while significantly mitigating its inherent issues of irritation and toxicity.[7]

A critical aspect of Povidone's profile is the nuanced nature of its safety, which is highly dependent on its molecular weight and route of administration. While generally recognized as safe for oral and topical use, parenteral administration of high-molecular-weight grades of Povidone is associated with significant risks of bioaccumulation and organ damage. This has led to decisive regulatory actions, including the withdrawal of intravenous products containing Povidone by the U.S. Food and Drug Administration (FDA) and the suspension of certain oral methadone formulations by the European Medicines Agency (EMA).[1] The clinical perspective on Povidone-Iodine's efficacy in wound healing also continues to evolve, with ongoing debate and research. Concurrently, the Povidone polymer is being explored for emerging applications in advanced drug delivery systems and nanotechnology, signaling a dynamic future for this established compound.[6]

Identification and Physicochemical Profile

Nomenclature and Chemical Identifiers

To establish the substance's identity, a systematic list of its names and chemical identifiers is essential.

• Primary Name: Povidone.[1]
• Systematic (IUPAC) Name: 1-Ethenylpyrrolidin-2-one.[3]
• Chemical Name: 1-ethenyl-2-pyrrolidinone homopolymer. It is a vinyl polymer composed of repeating -CH2-CR- units, where R is a 2-oxopyrrolidin-1-yl group.[1]
• Common Synonyms: Polyvinylpyrrolidone (PVP), Polyvidone, Polividone, Povidona, Povidonum, and the trade name Kollidon.[1]
• CAS Number: 9003-39-8.[3]
• DrugBank ID: DB11061.[1]
• Molecular Formula: (C6​H9​NO)n​. The subscript 'n' signifies its polymeric nature, indicating a repeating chain of monomers.[2]
• Food Additive E Number: E1201.[3]

Molecular Structure and Synthesis

Povidone is a homopolymer synthesized from the monomer N-vinylpyrrolidone.[1] The structure of its repeating unit, the pyrrolidone ring, contains both a hydrophobic alkyl group and a polar amide group. This dual chemical nature is the basis for its unique solubility in a wide range of polar and non-polar solvents, a key factor in its widespread utility.[6]

The industrial manufacturing of Povidone is accomplished via the multi-step Reppe process, which involves [12]:

1. Butynediol Formation: Acetylene and formaldehyde are reacted in the presence of a highly active copper acetylide catalyst to form butynediol.
2. Hydrogenation: The butynediol is hydrogenated to produce butanediol.
3. Cyclodehydrogenation: Butanediol is then converted via cyclodehydrogenation into butyrolactone.
4. Pyrrolidone Production: Butyrolactone is reacted with ammonia to yield pyrrolidone.
5. Vinylation: The pyrrolidone undergoes a vinylation reaction with acetylene under pressure, creating the monomer N-vinylpyrrolidone.
6. Polymerization: Finally, the N-vinylpyrrolidone monomer is polymerized, typically in an aqueous solution using a catalyst system such as ammonia and hydrogen peroxide, to produce the final Povidone polymer. The polymer is then isolated, often by spray-drying.[12]

Physicochemical Properties

• Physical Appearance: Povidone is a white or nearly white, light, flaky, and amorphous powder.[2]
• Hygroscopicity: It is a notably hygroscopic substance, capable of readily absorbing up to 40% of its weight in atmospheric water. This property is critical to its function as a disintegrant but also necessitates careful storage in airtight containers.[3]
• Solubility: Povidone exhibits excellent solubility in water and alcohols like ethanol, while being insoluble in solvents such as ether. This amphiphilic character allows it to be used in diverse formulation environments.[2]
• Melting Point: The melting point is approximately 100°C, although as a polymer, it may decompose at higher temperatures.[2]
• pH: In a 5% aqueous solution, Povidone exhibits a pH in the range of 3.0 to 7.0.[2]
• Molecular Weight (K-Value): Povidone is not a single molecule but a distribution of polymer chains of varying lengths. It is commercially available in different grades, characterized by a K-value, which is derived from viscosity measurements and correlates to the mean molecular weight. Common grades include K15 (average MW ~10,000), K25, K30 (average MW ~40,000), and K90.[3] The selection of a specific K-value is a critical decision in formulation development, as the molecular weight directly dictates the polymer's viscosity, binding strength, and physiological behavior.[5]

Povidone as a Multifunctional Pharmaceutical Excipient

The immense value of Povidone as a pharmaceutical excipient stems from its versatile and tunable physical properties. By selecting a specific grade, or K-value, formulators can precisely tailor its function to meet the demands of a particular dosage form. For instance, higher K-value grades like K90 offer very strong binding properties but are used in smaller concentrations; their high molecular weight also prevents renal excretion, making them unsuitable for parenteral applications and a subject of regulatory scrutiny.[10] In contrast, lower K-value grades are more common and versatile. This ability to "tune" the polymer's performance by controlling its molecular weight is the foundation of its indispensability in modern pharmaceutics.

Role in Solid Dosage Formulations

• Binder: Povidone is one of the most frequently used binders in the manufacture of pharmaceutical tablets. It imparts the necessary mechanical strength and integrity to prevent tablets from breaking or crumbling during production, packaging, and transport.[1] Its strong adhesive properties are effective in wet granulation (using either water or alcohol as the granulating fluid), dry granulation, and direct compression manufacturing processes.[5] The ability to use an alcohol-based solution makes Povidone an ideal binder for drugs that are sensitive to water or heat.[5]
• Disintegrant: The hygroscopic nature of Povidone allows it to function as a tablet disintegrant. When the tablet is ingested, the Povidone absorbs water, swells, and thereby forces the tablet matrix to break apart, facilitating the release and dissolution of the active drug.[4] A specialized, cross-linked, and water-insoluble form of Povidone, known as Crospovidone (PVPP), is particularly effective and widely used as a "superdisintegrant" for its outstanding performance.[3]
• Solubilizer and Dispersion Agent: Povidone's unique solubility in both aqueous and lipid-based solvents makes it an excellent vehicle for dispersing and suspending drugs, especially those with poor water solubility.[2] It can be used as a coprecipitating agent, where the drug is molecularly dispersed within the polymer matrix, significantly enhancing its dissolution rate and bioavailability.[5]

K-Value	Approximate Average Molecular Weight	Primary Pharmaceutical Applications
K15	10,000	Suspending agent, viscosity modifier, film former in ophthalmic solutions.16
K17	-	Binder, disintegrant, and stabilizer in tablet formulations.19
K25	-	Common binder for tablets and capsules, film former, flavoring aid.17
K30	40,000	Most widely used grade for wet binding in tablets; cosolvent and stabilizer.5
K90	360,000	High-adhesion binder for tablets requiring strong binding at low concentrations.12

Applications in Liquid, Ophthalmic, and Topical Formulations

• Ophthalmic Lubricant: Povidone is a primary active ingredient in numerous over-the-counter ophthalmic preparations, commonly known as "artificial tears".[1] These products provide symptomatic relief for dry, irritated eyes by keeping the ocular surface moist, protecting it from injury, and alleviating symptoms such as burning, itching, and the sensation of a foreign body in the eye.[20] It is often formulated in combination with other lubricants like dextran, polyethylene glycol 400, and polyvinyl alcohol.[1] Beyond eye drops, Povidone is also incorporated into some contact lenses and their packaging solutions to act as a built-in wetting agent, reducing friction against the cornea.[3]
• Suspending and Dispersing Agent: In oral liquids and suspensions, Povidone serves to maintain uniform distribution of the active drug particles and modifies the viscosity of the formulation for better pourability and mouthfeel.[2]
• Film-Forming Agent: Povidone's ability to form clear, flexible films upon drying is leveraged in several applications. It is used in tablet coatings, in transdermal patches as an adhesive component, and in topical gels.[3] This same property is exploited in many personal care products, most famously as the basis for early hair sprays and gels.[3]

Emerging Roles in Advanced Drug Delivery

The favorable biological and chemical properties of Povidone—including its established safety in oral use, non-carcinogenic nature, biocompatibility, and versatile solubility—position it as a highly attractive polymer for the development of advanced drug delivery systems (DDS).[6] Research is actively exploring its use in the synthesis of micro- and nanoparticles. These nanocarriers can be loaded with either hydrophobic or hydrophilic drugs, potentially shielding the body from the toxicity of potent compounds while enabling targeted delivery.[6] Its high capacity for water absorption also makes it a suitable material for creating hydrogels for controlled-release applications.[6]

The Povidone-Iodine Complex: Pharmacology and Clinical Antiseptic Applications

The development of Povidone-Iodine represents a landmark achievement in pharmaceutical formulation science. Elemental iodine has been recognized for over a century as a powerful, broad-spectrum microbicide, but its clinical utility was severely limited by significant drawbacks, including skin irritation, systemic toxicity, tissue staining, and chemical instability.[7] Povidone, which on its own possesses no antimicrobial activity, provided the solution.[1] By complexing iodine with the large Povidone polymer, an "iodophor" was created. In this complex, the Povidone acts as a carrier and a solubilizing agent, creating a stable, water-soluble reservoir.[1] This formulation does not neutralize the iodine but rather controls its availability, allowing for a gradual and sustained release of free iodine at the site of application.[1] This mechanism successfully "tamed" the wild element, preserving its potent antiseptic effect while dramatically reducing its undesirable properties. Povidone-Iodine is a classic example of how polymer chemistry can transform a problematic but powerful active ingredient into a safe, effective, and clinically indispensable product.

The Iodophor Complex

Povidone-Iodine (PVP-I), also known as iodopovidone, is a stable chemical complex of polyvinylpyrrolidone and elemental iodine, discovered in 1955.[8] Formulations typically contain between 9.0% and 12.0% of available iodine, calculated on a dry basis.[8] In this complex, Povidone functions as an iodophor (iodine carrier), which solubilizes the iodine and acts as a reservoir, ensuring a slow and continuous release of the active agent.[1]

Mechanism of Antimicrobial Action

The potent microbicidal activity of Povidone-Iodine is mediated entirely by the free iodine that is gradually liberated from the polymer complex at the application site; the Povidone carrier is pharmacologically inert.[1] Once released, free iodine rapidly penetrates the cell walls of a broad spectrum of microorganisms, including bacteria (Gram-positive and Gram-negative), fungi, viruses, protozoa, and spores.[8]

The lethal effect of iodine is multifactorial and non-specific, which helps to prevent the development of microbial resistance. Its mechanisms include [7]:

• Oxidation of cytoplasmic and membrane compounds.
• Iodination of membrane lipids and proteins, disrupting their structure and function.
• Disruption of protein and nucleic acid synthesis.
• Denaturation and deactivation of critical cytosolic enzymes, particularly those involved in the respiratory chain.

This broad, rapid, and potent mechanism of action is a key advantage. Notably, unlike many antibiotics such as mupirocin, there have been no available reports linking the use of Povidone-Iodine to the induction of bacterial resistance or cross-resistance to other antimicrobials.[23]

Clinical Indications and Therapeutic Formulations

Povidone-Iodine is indicated for a wide array of antiseptic uses.

• First Aid: Its primary over-the-counter use is for inducing antisepsis to prevent infection in minor cuts, scrapes, and burns.[1]
• Surgical Antisepsis: It is a mainstay in clinical settings for pre- and post-operative skin disinfection and as a surgical scrub for the hands of healthcare providers. Its sustained-release properties provide a longer-lasting antiseptic effect, making it particularly suitable for lengthy surgical procedures.[7]
• Ophthalmology: A buffered 2.5% solution is used as a prophylactic treatment to prevent neonatal conjunctivitis, particularly when caused by Neisseria gonorrhoeae or Chlamydia trachomatis.[7]
• Gynecology: It is formulated into vaginal pessaries, suppositories, or solutions for the treatment of vaginitis and for general vulvar cleansing.[1]
• Oral Health: Diluted solutions (e.g., 1%) can be used as a mouthwash or gargle for the symptomatic treatment of sore throat, pharyngitis, and other oral cavity infections.[26]
• Pleurodesis: It is used as a sclerosing agent to fuse the pleural layers in patients with recurrent pleural effusions, offering an effective and low-cost alternative to talc.[3]

It is available in numerous formulations, including topical solutions (commonly 10%), ointments, creams, dry powder sprays, liquid soaps, surgical scrubs, and pessaries.[1]

Clinical Efficacy and Controversies

Despite its widespread and long-standing use, the clinical effectiveness of Povidone-Iodine, particularly concerning its impact on wound healing, remains a subject of debate.[1] Several clinical studies have reported that while effective at preventing infection, the application of Povidone-Iodine to wounds was associated with impaired or slower healing, reduced wound tensile strength, and mild to moderate patient discomfort.[1] This suggests that its cytotoxicity, while reduced compared to tincture of iodine, may still be sufficient to harm fibroblasts and other cells critical to the healing process.

Conversely, other analyses highlight its beneficial tolerability and potential to accelerate wound healing.[28] However, a recent comprehensive scoping review concluded that high-quality evidence supporting its efficacy in wound care outcomes is limited and often controversial.[28] Furthermore, there is strong evidence indicating that for pre-operative skin preparation, a combination of chlorhexidine and alcohol is superior to any Povidone-Iodine formulation.[7] This discrepancy between its ubiquitous use and the quality of evidence supporting its superiority over modern alternatives represents a significant point of discussion in clinical practice.

Comprehensive Safety and Toxicology Assessment

The safety profile of Povidone is not absolute but is critically dependent on its physicochemical properties—specifically its molecular weight—and the route of administration. A substance generally considered safe and inert when used as an oral excipient can become a significant health hazard when introduced systemically. The regulatory actions taken by both the FDA and EMA underscore this principle. The primary risk associated with Povidone itself is not inherent chemical toxicity but rather biopersistence. High-molecular-weight polymer chains are too large to be filtered and excreted by the kidneys.[17] When administered intravenously, or when oral formulations are misused via injection, these large polymers are taken up by the reticuloendothelial system and become sequestered in organs such as the liver, spleen, and lungs, where they can cause granulomatous lesions and long-term organ damage.[12] This "inactive excipient paradox" demonstrates that the safety of a pharmaceutical ingredient cannot be divorced from its physical characteristics and intended use.

Povidone (as an Excipient)

• Oral and Topical Safety: When used as intended in oral and topical formulations, Povidone is considered biologically inert and generally safe.[3] In cases of large accidental ingestion, only minimal symptoms, such as diarrhea, are expected.[31]
• Parenteral Safety Concerns: The FDA has withdrawn its approval for all intravenous drug products containing Povidone.[1] This decision followed evidence from its historical use as a plasma volume expander, which was discontinued because the polymer was found to accumulate in the liver and spleen.[3]
• High Molecular Weight Risk (EMA Action): In Europe, the EMA suspended marketing authorization for oral methadone solutions formulated with high-molecular-weight Povidone (K90). This action was prompted by reports of serious adverse events, including fatalities, in individuals who misused the oral solution by injecting it. The high-MW Povidone accumulated in vital organs, leading to severe harm. In contrast, methadone tablets formulated with lower-molecular-weight Povidone, which can be renally excreted, were allowed to remain on the market with updated warnings.[10]
• Risks from Misuse: Autopsy reports of substance abusers who have injected crushed pharmaceutical tablets have shown that the excipient crospovidone (PVPP) contributes to pulmonary vascular injury.[3] Chronic inhalation of Povidone dust has also been linked to interstitial fibrosis in the lungs.[12]

Povidone-Iodine (as an Antiseptic)

The safety concerns for the Povidone-Iodine complex are primarily related to the iodine component.

• Adverse Effects: The most common side effects are local and generally mild, including temporary burning, stinging, irritation, redness, or dryness at the application site.[20] Skin swelling can also occur.[7] While rare, serious allergic reactions (anaphylaxis) are possible in sensitized individuals.[20]
• Systemic Iodine Toxicity: This is the most significant risk associated with Povidone-Iodine, occurring when it is used over large areas of compromised skin (e.g., large wounds, severe burns) or for prolonged periods. The systemic absorption of iodine can lead to serious complications, including metabolic acidosis, hypernatremia (high blood sodium), and acute kidney injury.[7] Patients with pre-existing kidney dysfunction are at a higher risk.[31]
• Carcinogenicity: The toxicological data is conflicting. One source lists Povidone as a "questionable carcinogen".[12] However, multiple material safety data sheets and toxicological reviews do not classify Povidone or Povidone-Iodine as a carcinogen.[34] This discrepancy warrants caution, though the weight of evidence does not support a strong carcinogenic link.
• Toxicological Data (LD50​): Acute oral toxicity is low. The oral median lethal dose (LD50​) for Povidone-Iodine is reported as >8000 mg/kg in rats and 8100 mg/kg in mice.[36] For Povidone alone, the oral LD50​ is reported as >40 mg/kg in mice and 100 mg/kg in rats.[1]

Contraindications, Warnings, and Interactions

• Contraindications: Povidone-Iodine is contraindicated in individuals with a known allergy or sensitivity to iodine.[38] It should also be avoided in patients with hyperthyroidism or other active thyroid disorders and in those with the blistering skin condition dermatitis herpetiformis.[7] Its use is not recommended in pregnant women at less than 32 weeks of gestation, and frequent use should be avoided in patients taking lithium.[7]
• Warnings: Povidone-Iodine products are for external use only. They should not be used on deep puncture wounds, animal bites, or serious burns without consulting a healthcare professional.[27] Unless directed by a clinician, use should be limited to one week and should not be applied over large areas of the body.[32] It is also important to note that non-sterile Povidone-Iodine has a documented history of intrinsic contamination with opportunistic pathogens like Burkholderia cepacia, which are resistant to the antiseptic. This underscores the critical importance of using sterile products for all clinical applications.[7]
• Interactions: The antiseptic activity of iodine is neutralized by reaction with substances like hydrogen peroxide, silver (found in some wound dressings), and the antiseptic taurolidine. Povidone-Iodine also reacts with mercury compounds to form corrosive mercury iodide and is incompatible with many metals, making it unsuitable for disinfecting certain piercings.[7] If significant systemic absorption occurs, the iodine can interfere with thyroid function tests and other diagnostic tests that rely on iodine uptake.[7]

Feature	Povidone (as Excipient)	Povidone-Iodine (as Antiseptic)
Primary Safety Concern	Bioaccumulation of high-molecular-weight grades with parenteral/IV administration or misuse, leading to organ damage.10	Systemic iodine toxicity from absorption through large wounds or burns, leading to renal and metabolic complications.7
Common Adverse Effects	Generally inert via oral route; large ingestions may cause diarrhea.31	Local skin irritation, redness, dryness, burning/stinging sensation.20
Key Contraindications	Intravenous administration is withdrawn. High-MW grades are contraindicated in formulations at risk of injection misuse.1	Iodine allergy, hyperthyroidism, dermatitis herpetiformis.7
Significant Interactions	None well-documented for the polymer itself.	Inactivated by hydrogen peroxide, silver. Reacts with mercury compounds. Interferes with thyroid function tests.7

Regulatory Status and Clinical Research Landscape

Global Regulatory Standing

• U.S. Food and Drug Administration (FDA): Povidone is an approved excipient found in a vast number of pharmaceutical products.[4] Povidone-Iodine is widely available over-the-counter (OTC) and is marketed under an OTC drug monograph which, as of recent reports, is not yet finalized. This means that while products must comply with federal regulations, they are not typically subject to individual pre-market review and approval by the FDA.[24] The agency has issued public health warnings against unregistered Povidone-Iodine products sold in the market, stating that their quality and safety cannot be assured.[41] The FDA has also taken enforcement action, such as issuing warning letters, against companies making unapproved claims that their Povidone-Iodine products can prevent or treat diseases like COVID-19, classifying these as unapproved new drugs that are not generally recognized as safe and effective (GRASE) for such purposes.[43] Critically, the FDA previously withdrew its approval for all intravenous drug products containing Povidone due to safety concerns related to bioaccumulation.[1]
• European Medicines Agency (EMA): The EMA has also taken significant regulatory action related to Povidone's safety. Following a review by its Pharmacovigilance Risk Assessment Committee (PRAC), the Coordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh) endorsed the suspension of marketing authorizations for oral methadone solutions containing high-molecular-weight Povidone. This was a direct response to safety risks identified from the intravenous misuse of these oral products.[10] More recently, in December 2023, the EMA's Paediatric Committee granted a product-specific waiver for iodinated Povidone eye drops intended for preoperative use in children, on the grounds that the product did not offer a significant therapeutic benefit over existing treatments.[44]

Review of Clinical Trials

The landscape of clinical research involving Povidone reflects an evolving understanding and application of the polymer and its complexes. The focus of investigation has shifted over time from broad, exploratory studies to more targeted trials aimed at validating its role in areas of significant clinical need and controversy.

• Historical and Completed Trials: Povidone has been a component in trials across a diverse range of medical fields. These include a terminated trial investigating its use for migraines [45], a completed Phase 3 trial where it was part of a combination product (Cytoflavin®) studied for the prevention of post-operative cognitive decline in elderly patients [46], and a completed Phase 4 trial examining a combination of Povidone-Iodine, honey, and lidocaine for enhancing the healing of perineal tears.[47] This variety suggests a period of broad interest in its potential applications.
• Active and Recent Trials: Contemporary research is highly focused on rigorously evaluating the established antiseptic properties of the Povidone-Iodine complex in response to major public health challenges.
• Surgical Site Infections (SSIs): An active and recruiting multicenter Phase 3 randomized controlled trial (NCT06363877) is directly comparing the efficacy of intraoperative irrigation with dilute Povidone-Iodine versus normal saline for the prevention of SSIs in patients undergoing emergency laparotomies. This study aims to provide high-quality evidence to address the ongoing clinical debate regarding Povidone-Iodine's superiority in surgical settings.[48]
• Virucidal Activity: In response to the COVID-19 pandemic, a randomized clinical trial (NCT04549376) was initiated to assess the in-vivo virucidal effect of Povidone-Iodine administered as a nasal irrigation or spray on SARS-CoV-2 in the nasopharynx of infected patients. This research reflects the scientific community's effort to repurpose existing, readily available agents with known antiviral properties for pandemic preparedness and response.[49]

This shift in clinical trial focus from broad discovery to targeted validation indicates a maturation in the product's life cycle. The research community is no longer exploring wholly new uses for the Povidone polymer itself, but is instead working to define the precise role and optimize the application of the Povidone-Iodine complex within the modern medical armamentarium, particularly for infection control and viral decontamination.

Conclusion and Future Directions

Povidone has traced a remarkable path from its early, unsuccessful application as a blood plasma substitute to its current status as both an indispensable pharmaceutical excipient and the foundational carrier for a globally recognized antiseptic. Its dual identity is its defining characteristic. As an excipient, its value lies in its chemical stability, safety in oral use, and tunable molecular weight, which allows it to be adapted for myriad functions in drug formulation. As the partner to iodine, it transformed a potent but harsh element into a manageable and effective clinical tool.

This analysis has highlighted the critical dichotomies that define Povidone: the profound difference in safety between its oral and parenteral use, which is dictated by molecular weight; and the contrast between the undisputed in vitro microbicidal power of Povidone-Iodine and the persistent clinical debate surrounding its true impact on wound healing compared to modern alternatives.

Looking ahead, the future of Povidone and its complexes appears to be advancing along several key fronts:

• Nanotechnology and Drug Delivery: The inherent properties of the Povidone polymer—biocompatibility, versatile solubility, and safety—make it an ideal platform for innovation in nanotechnology. Future research will likely focus on developing Povidone-based nanoparticles and hydrogels as sophisticated drug delivery systems for targeted therapies, controlled release, and the formulation of otherwise difficult-to-deliver drugs.[6]
• Antimicrobial Stewardship: In an era of escalating antimicrobial resistance, the role of broad-spectrum antiseptics that do not induce resistance, like Povidone-Iodine, is of increasing importance. It remains a valuable tool for infection prevention.[23] However, its optimal place in clinical practice requires further clarification. High-quality, large-scale clinical trials, such as the ongoing study on surgical site infections [48], are essential to definitively establish its efficacy relative to other agents like chlorhexidine and to guide evidence-based clinical guidelines.
• Pandemic Preparedness: The investigation into Povidone-Iodine's virucidal effects against respiratory pathogens like SARS-CoV-2 has opened a potential new application in public health.[43] If validated by further clinical research, the use of Povidone-Iodine nasal or oral rinses could become part of a multi-layered strategy to reduce viral transmission and decontaminate the upper airways during future viral outbreaks.

In conclusion, Povidone is a mature and well-established polymer, yet its story is far from over. While its role as a workhorse excipient is secure, its future impact will likely be shaped by its application in advanced material science and its continued evaluation as a frontline agent in the global fight against infection.

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