Amoxicillin clavulanate nasal spray

Abstract

This invention describes a novel, stable, fixed-dose, aqueous suspension of Amoxicillin Clavulanate for nasal administration to treat post-surgical nasal infections. The formulation leverages a unique combination of excipients, including mucoadhesive agents like chitosan, to enhance drug delivery and efficacy. Key features include targeted delivery to the infection site, sustained release for reduced dosing frequency, and the ability to disrupt bacterial biofilms. This innovative approach addresses the limitations of current treatment options by providing effective local drug delivery, minimizing systemic side effects, and improving patient compliance.

Description

[0001] FORM 2 PATENTS ACT, 1970 (39 of 1970) & The Patents Rules, 2003 COMPLETE SPECIFICATION (See section 10 and rule 13) 1. TITLE OF THE INVENTION 2. APPLICANTS a) Name : AODH LIFESCIENCES PRIVATE LIMITED b) Nationality : INDIAN c) Address : II Floor, 12-5-32 / 8, Next to Abbott India, Vijayapuri, Tarnaka, Secunderabad, Telangana - 500017, India. 3. PREAMBLE TO THE DESCRIPTION COMPLETE The following specification particularly describes the invention and the manner in which it is to be performed.

[0002] 5 10 15 20 25 Conventional systemic or oral antibiotic therapies for post-surgical nasa l infections 5 face several limitations, including the development of antibiotic-resistant bacteria due to widespread use, which can lead to prolonged infections and complications when resistant strains fail to respond to standard treatments like oral amoxicillin-clavulanate. Additionally, these therapies often cause systemic side effects, such as gastrointestinal disturbances, allergic reactions, and antibiotic-associated diarrhea, which can hinder 10 patient recovery in the post-surgical context. The delayed therapeutic action of systemic antibiotics, which must traverse the bloodstream to reach the nasal cavity, can allow infections to worsen, while the inadequate local concentration of antibiotics may fail to eradicate infections, especially in the presence of biofilms. These biofilms act as barriers, protecting bacteria from antibiotics and contributing to chronic infections that 15 may require further surgical interventions. While drug-eluting stents show promise, their long-term efficacy remains under investigation, and they are costly and not universally suitable, further limiting the available treatment options. A targeted solution for post-surgical nasal infections offers several advantages over conventional treatments. By enabling direct delivery of antimicrobial agents to the 20 infection site, such as through a nasal spray, it ensures high local drug concentrations while minimizing systemic exposure, reducing side effects like gastrointestinal disturbances and allergic reactions. This localized approach enhances effectiveness against infections, particularly in the complex nasal anatomy, and improves biofilm penetration, ensuring thorough eradication of resistant bacterial colonies. Use of these 25 targeted agents can significantly lower the risk of post-operative infections, especially in high-risk surgeries, improving patient outcomes, accelerating recovery, and reducing the need for additional interventions. Furthermore, resistance management strategies, such as the use of novel antimicrobials or combination t herapies , he lp m itigate t he risk of antibiotic resistance, enhancing long-term treatment efficacy wh ile reducing ove rall healthcare costs. 5 10 15 20 25

[0003] 10 15 20 25 5

[0004] 10 15 20

[0005] 5 10 In one emb odiment, the composition comprises amoxicillin as the active pharmaceutical ingredient in one or more of its approved salt forms, including amoxicillin trihydrate, amoxicillin sodium, and amoxicillin potassium. These salts are selected based on their stability, solubility, and compatibility in a suspension formulation. In a preferred example, amoxicillin trihydrate is utilized due to its 15 excellent stability in aqueous environments, non-irritating nature, and suitability for long-term storage. Alternatively, amoxicillin sodium can be employed in formulations designed for rapid therapeutic action, while amoxicillin potassium may be considered for its specific compatibility with other components in the formulation. These salts ensure optimal antibacterial activity and uniformity in the nasal spray suspension.20In one embodiment, the composition further comprises clavulanate, a β-lactamase inhibitor, in one or more of its approved salt forms, including potassium clavulanate, clavulanate sodium, and clavulanate magnesium. Among these, potassium clavulanate is preferred for its superior solubility and stability in aqueous formulations, making it 25 ideal for nasal spray suspensions. Alternatively, clavulanate sodium may be employed in formulations requiring rapid action against β-lactamase-producing bacteria, while clavulanate magnesium is a viable option for specific applications where additional stability or solubility advantages are desired. These salts ensure that the amoxicillin component is protected from enzymatic degradation, thereby enhancing the efficacy of the formulation in treating upper respiratory tract infections . 5 10 15 20 25 8 5 10 15 20 25 9 5 10 15 20 25 5 10 15 2025

[0006] 5 10 15 20 12 5 10 15 20 25 Provided herein are, for example, pharmaceutical spr ay formulation s of Amoxicillin and Clavulanate. 5 10 15 20 25 14 5 10 In the context of th e present invention, the term “Suspending agent” refers to a substance that stabilizes a suspension by increasing its kinetic stability. Suspending agents are used to increase the viscosity of a liquid, helping to stabilize suspensions by 15 keeping insoluble particles evenly distributed and preventing them from settling. This results in a stable dispersion of small droplets of one phase within the other, preventing the phases from separating. Suspending agents are commonly used in pharmaceutical compositions to ensure uniform distribution of active ingredients and enhance the consistency and stability of the formulation. Non-limiting examples of Suspending 20 agents include polysorbates (e.g., polysorbate 80), sorbitan esters (e.g., sorbitan monolaurate), lecithin, xanthum gum, and various polyoxylated fatty acid derivatives, cellulose derivatives like microcrystalline cellulose and sodium carboxymethylcellulose (Avicel RC-591), hydroxypropyl methylcellulose (HPMC), and methylcellulose. Polysaccharides such as xanthan gum and carrageenan, along 25 with natural gums like acacia and tragacanth, are also prevalent. Synthetic polymers like carbomers (Carbopol) and polyvinyl compounds such as polyvinyl alcohol (PVA) and polyvinylpyrrolidone (PVP) are employed for their stabilizing properties. Inorganic agents like colloidal silicon dioxide and magnesium aluminum silicate are sometimes used for additional stabilization. Surfactants such as polysorbates (e.g., Polysorbate 80) 5 10 15 2025 5 10 152025 5 10 15 20 25 5 10 15 20 25 5 Edetate disodium (EDTA) is in cluded in the formulation primarily as a chelating agent due to its ability to bind divalent metal ions such as calcium and magnesium, which play a critical role in stabilizing bacterial cell walls and biofilm structure. In addition to its chelating properties, EDTA also exhibits a significant biofilm- 10 disrupting activity, effectively breaking down the extracellular polymeric substances (EPS) that form the structural matrix of bacterial biofilms. This dual functionality enhances the overall antimicrobial efficacy of the nasal spray formulation by improving penetration and activity of the active pharmaceutical ingredients against biofilm- embedded bacteria. The concentration of EDTA in the aqueous nasal spray suspension 15 ranges from approximately 0.1% w / v to 0.5% w / v, relative to the total weight of the composition, ensuring optimal performance without compromising the safety or stability of the formulation. Examples of such suitable chelating agents which can be employed in the aqueous nasal spray suspension include, but are not limited to, edetate disodium (EDTA), edetate trisodium, edetate tetrasodium, and diethyleneamine 20 pentaacetate, preferably EDTA. Examples of suitable sweetener / taste masking agents that can be employed in the aqueous nasal spray suspension include, but are not limited to, sucralose, thaumatin (e.g., Talin(R)), sucrose, saccharin (including salt forms such as sodium and calcium 25 salts), fructose, glucose, dextrose, corn syrup, aspartame, acesulfame-K, xylitol, sorbitol, erythritol, ammonium glycyrrhizinate, neotame, mannitol, eucalyptus oil, camphor, and natural or artificial flavors or flavoring agents (for example, menthol, mints, vanilla, orange, etc.), or combinations of two or more of such agents. A particula rly preferred tas te-masking agent is su cralose. The amount of the sweetener / tas te maskin g agent pres ent i n the aqu eo us nasal spray suspensi o n m ay r ange from about 0.01% t o about 1% w / w r elative to the tota l weight of the composition. 5 10 15 20 25 5 10 15 20 25 5 10 15 2025 5 10 15 20 25 24 5 10 15 2025 5 10 15 20 25 26 5 10 12 Citric acid 0.05-0.1% w / v p (mg / 100 µL) Infection Infection Manufacturing Steps: 1. Preparation of Chitosan Solution: 5 o Dissolve the required amount of chitosan (1.0 mg) in a small volume of purified water (acidified to pH 5.0 with citric acid) under gentle stirring. o Allow the solution to hydrate for 2–3 hours or until fully dissolved. 2. Preparation of Polymer and Viscosity Enhancer Solution: o In a separate vessel, dissolve polyvinyl alcohol (1.5 mg), poloxamer 407 10 (1.5 mg), carbopol (0.3 mg), and xanthan gum (0.3 mg) in a portion of purified water under constant stirring.oHeat the solution to 50–60°C to ensure complete dissolution of the polymers. o Cool the solution to room temperature before proceeding. 3. Preparation of Buffer and Stabilizing Solution: o Dissolve citric acid (0.075 mg) and EDTA (0.2 mg) in a separate portion of purified water. o Adjust the pH of the solution to 6.5–7.5 using sodium hydroxide or hydrochloric acid as needed. 4. Preparation of Surfactant Solution: o Dissolve polysorbate 80 (0.5 mg) and glycerin (2.0 mg) in purified water under gentle stirring. 5. Incorporation of Active Pharmaceutical Ingredients (APIs): o Add amoxicillin (0.53 mg) and clavulanate (0.27 mg) to the polymer- viscosity enhancer solution (from Step 2) under stirring until fully dissolved. 6. Combination of Solutions: o Gradually combine the chitosan solution (Step 1), buffer solution (Step 3), and surfactant solution (Step 4) into the API-polymer solution (Step 5). o Use a high-shear homogenizer for 5–10 minutes to ensure a uniform suspension. 7. Filtration: o Pass the combined solution through a 0.22 µm sterile filter to remove any par ticula te matter and ensure sterility. 8. Filling into N o Fill the asal Spray Devices: sterile filtered suspensio n into p re- sterilized metered-d ose nasa l spray devices under a l aminar flow hood. o Each spray is calibrated to deliver 100 µL per actuation Final Checks: . 9. o Perfo rm pH and vis cosity measurem ents to ens ure the formulation is within specified ranges. o Check for uniformity and absence of phase separation by visual inspection. o Perform microbiological testing to confirm sterility. Stability Study Data Major Axis (mm) 58 68 62 57 1.1 Related Substances for Amoxicillin Clavulanate Impurity A (%) Total impurities (%) 0.25 0.31 0.60 D10 (μm) 21.91 21.39 20.15 by Brookfield viscometer. 5 SN Ingredient Concentration (w / v) Physical observation on standing for 24 hours. No phase separation Observed ^ Preparation of HPMC Solution: ^ Gradually disperse HPMC (0.5–2% w / v) into purified water under stirring to 5 avoid clumping. ^ Heat the mixture to 60–70°C to dissolve the polymer completely. ^ Allow the solution to cool to room temperature. ^ Preparation of Stabilizer and Buffer Solution: ^ Dissolve citric acid (0.1–0.3% w / v) and N-acetylcysteine (0.1–0.5% w / v) in 10 a separate portion of purified water under gentle stirring. ^ Incorporation of Surfactant: ^ Add polysorbate 80 (0.05–0.1% w / v) to the stabilizer solution while stirring continuously to ensure uniform dispersion. ^ Preparation of API Solution:15 ^Dissolve amoxicillin (0.001–4.87% w / v) and clavulanate (0.001–2.13% w / v) in purified water. ^ Add the API solution to the buffer-stabilizer solution (from Step 2) under continuous stirring. ^ Incorporation of Magnesium Stearate:20 ^Disperse magnesium stearate (0.1–0.3% w / v) into the HPMC solution (Step 1) using a high-shear homogenizer to ensure even distribution. ^ Combination of Solutions:^Gradually combine the API-buffer solution (Step 4) and the HPMC- magnesium stearate solution (Step 5). ^ Mix using a high-shear homogenizer for 10–15 minutes to form a uniform suspension. 5 ^ Adjustment of Viscosity and pH: ^ Add glycerine (2–5% w / v) to the combined solution and adjust the pH to 6.5– 7.5 using sodium hydroxide or hydrochloric acid as required. ^ Filtration: ^ Pa ss the fina l formu lation through a 0.22 µm sterile filter t o en sure ste ril ity 10 and re move particu lates. ^ Filling into Nasal S pr ay Devices: ^ Un der a laminar flow hood, fill the sterile filtered suspension into pre- sterilized metered-dose nasal spray devic ^ Each spray sh es. o uld deliver 100 µL per actua tio n. 15 35 36 5 1. Preparation of Stabilizer Solution: o Dissolve citric acid (0.1–0.3% w / v), sodium chloride (0.5–0.9% w / v), and calcium chloride (0.05–0.1% w / v) in purified water under gentle 5 stirring. 2. Preparation of Mucoadhesive and Thickening Agents: o Gradually add sodium hyaluronate (0.1–0.5% w / v) and xanthan gum (0.2–0.4% w / v) to a separate portion of purified water under constant stirring to avoid clumping. Allow the mixture to hydrate for 1–2 hours until fully dissolved and homogenous. ration of N-Acetylcysteine (NAC): Dissolve NAC (0.1–0.5% w / v) into the stabilizer solution (from Step 1) while stirring gently. n of Surfactant and Lubricant: Add polysorbate 80 (0.05–0.1% w / v) and magnesium stearate (0.1– 0.3% w / v) to the mucoadhesive-thickener solution (from Step 2). Homogenize the solution using a high-shear homogenizer for 10 minutes to ensure uniform dispersion. ration of Active Ingredients (APIs): Dissolve amoxicillin (0.001–4.87% w / v) and clavulanate (0.001– 2.13% w / v) in purified water under stirring. Combine the API solution with the stabilizer-thickener mixture under continuous stirring. ation of All Solutions: Gradually combine the API-stabilizer mixture (Step 5) with the surfactant-thickener solution (Step 4). Homogenize the final mixture for 10–15 minutes to form a uniform suspension. ent of pH: Measure the pH of the suspension and adjust it to 6.5–7.5 using sodium hydroxide or hydrochloric acid, as required. iltration: Pass the final suspension through a 0.22 µm sterile filter to ensure sterility and remove any particulate matter. nto Nasal Spray Devices: Fill the sterile suspension into pre-sterilized metered-dose nasal spray devices under a laminar flow hood.

[0007] o Each s pray should de liver 100 µL per actu ation. 5 10 15 20 25 5 10 15 20 ^ Nasal Spray: The elimination of amoxicillin clavulanate when administered via nasal spray is primarily localized, with minim al systemic absorption leading to reduced engagement of the body's systemic elimination pathways. The drug is largely retained within the nasal cavity and sinus tissues, where it can be 25 metabolized locally or cleared through the mucociliary system. This localized elimination minimizes the burden on renal and hepatic systems, which is beneficial in reducing potential side effects associated with systemic drug clearance. The lower systemic absorption also means that less of the drug is available for excretion in urine or feces, making this route more suitable for localized infections that do not require widespread systemic treatment. ^ Oral: Amox icillin, when taken orally, is minimally metabolized and is primarily excreted unchanged in the urine, reflecting its systemic absorption 5 and distribution. Clavulanate, on the other hand, undergoes some hepatic metabolism and is excreted in both urine and feces. The oral administration of amoxicillin clavulanate involves systemic metabolism and elimination, which is effective for treating widespread infections but may not be ideal for localized post-surgical nasal infections. The systemic elimination pathways are more 10 engaged in oral administration, potentially leading to higher systemic side effects and less localized therapeutic effect within the nasal cavity. ^ Nasal Spray: The bioavailability of amoxicillin clavulanate in a nasal spray 15 formulation is tailored for loca lized delivery, focusing on achieving high concentrations at the site of infection rather than in the systemic circulation. The bioavailability in this context is more about the efficiency of drug deposition and retention within the nasal cavity and surrounding tissues. Due to the wound affinity and wound adhesion, the drug remains in contact with the 20 infected area for an extended period, which enhances local efficacy. While systemic bioavailability is lower compared to oral administration, this is an advantage for minimizing systemic side effects and focusing the therapeutic effect where it is most needed. ^ Oral: Oral amoxicillin clavulanate has a systemic bioavailability that is crucial 25 for treating infections that may extend beyond the local site. The bioavailability of amoxicillin is approximately 60-70%, and for clavulanate, it is around 30- 40%. This systemic absorption is important for addressing infections in multiple body tissues, but it is less efficient in achieving therapeutic concentrations specifically within the nasal cavity. The broad tissue distribution of the oral formulation may dilute the drug's presence in the nasal tissues, potentially reducing its effectiveness for localized infections like those that occur post-surgery in the nasal area. 5 10 15 20 25 5 10 15 20 25 45

[0008] 5 10 15 2025 The efficacy of various treatments in promoting sinonasal wound healing and tissue regeneration in an experimental rabbit model of mucosal injury was evaluated. Rabbits underwent mucosal injury induction, followed by the administration of a control, standard treatment(Oral amoxicillin clavulanate), or experimental doses of an 5 amoxicillin-clavulanate nasal spray. The wound healing process was assessed over five postoperative weeks through the measurement of three key parameters: Mean Defect Size Reduction (MDI): Dose 3 achieved the smallest defect size, indicating the most effective healing. Mean Mucosal Thickness Index (MTI): Dose 3 consistently showed higher MTI 10 values, signifying superior mucosal thickening. Ciliate d Ce l l Index ( C C I ) : D o s e 3 exhi b i te d the h i g h e st va l ue s , r ef le c t i n g e n h a n c e d 15 epithelial regeneration and thickening . Data were collected at weekly intervals to monitor the healing trajectory, emphasizing the potential of Dose 3 in accelerating wound closure, restoring mucosal integrity, and enhancing epithelial repair compared to control and standard treatment (Oral amoxicillin clavulanate). 20 25 5 The In Vitro Biofilm Disruption Study graph evaluates the efficacy of an amoxicillin- clavulanate formulation enha nced with "ASrMaBd" technology in disru pting biofilms of S. pneumoniae. Biofilms were cultured for two days before treatment, and their live 10 volume and bacterial viability were assessed 12 hours after administering Amoxicillin clavulanate nasal spray. The study revealed dose-dependent effects, with higher doses (Dose 1 to Dose 3) progressively reducing live biofilm volume and increasing dead biofilm volume in a New Zealand rabbit model. The technology-enhanced formulation facilitated deeper diffusion of amoxicillin-clavulanate into the biofilm, significantly 15 compromising its structural integrity and bacterial survival. These results highlight the formulation's potential in targeting resistant biofilms effectively. In Vivo Biofilm Disruption Study in New Zealand Rabbits: The In Vivo Biofilm Disruption Study graph illustrates the effectiveness of treatments in reducing biofilm thickness in S. pneumoniae-infected New Zealand rabbit sinusitis 20 models. The study compared oral azithromycin with the experimental Amoxicillin clavulanate nasal spray. Post-infection, rabbits were treated, and sputum samples were collected at hourly intervals to monitor biofilm formation and bacterial viability. Confocal Laser Scanning Microscopy (CLSM) was employed to measure biofilm thickness 25 The graph indicates a progressive decrease in biofilm thickness from Dose 1 to Dose 3 in the Amoxicillin clavulanate nasal spray group, highlighting its superior ability to disrupt biofilms compared to azithromycin. This demonstrates the nasal spray’s potential as an effective targeted treatment for bacterial sinusitis, promoting enhanced bacterial eradication in the infected sinus. 5 10 15 The study evaluates the mucoadhesive properties of Amoxicillin clavulanate Nasal Spray using an in vitro Porcine Mu cin Mod el. Two parameters, Adhesive W ork (Fig. 20 8) and Adhesive Force (Fig.9), were analyzed across 4 groups: Standard(Amoxicillin plain spray) and Test Groups 1–4 (n=5 per group). The experiment employed a texture analyzer, where a 2500 mN preload was applied to the nasal spray sample for 3 minutes. Following this, a cylinder probe with the Amoxicillin clavulanate nasal spray was lifted at a speed of 2.5 mm / min to detach the sample from the mucin surface. The 25 results show a progressive increase in adhesive work and adhesive force from Dose 1 to Dose 3, demonstrating dose-dependent mucoadhesion. These findings underline the strong binding capability of Amoxicillin clavulanate nasal spray, which could enhance retention in nasal applications. In vivo deposition study in New Zealand rabbits: The deposition study for Amoxicillin-Clavulanate Nasal Spray was conducted to evaluate its efficacy in enhancing drug deposition in the paranasal and maxillary 5 sinuses. This in vivo experiment utilized New Zealand White (NZW) rabbits (n=6) as the test species. The nasal spray formulation was administered intranasally, and drug deposition in the sinuses was assessed over a time course of 0 to 12 hours. Deposition levels were determined using high-sensitivity liquid chromatography-tandem mass spectrometry (LC-MS / MS). The experimental design included comparative groups: the 10 amoxicillin-clavulanate nasal spray and standard(Oral amoxicillin clavulanate). The study aimed to measure and compare the drug concentration achieved in the wound tissues, hypothesizing a statistically significant increase in deposition with the amoxicillin-clavulanate formulation compared to the standard. This approach highlights the potential of the nasal spray to improve localized antibiotic delivery 15 effectively. 20 25

Claims

5. CLAIMS I / We Claim:

1. A nasal spray pharmaceutical formulation comprising: 5 amoxicillin: 0.001–4.87% w / v clavulanate: 0.001–2.13% w / v chitosan: 0.5–2% w / v polyvinyl alcohol: 0.5–2% w / v EDTA: 0.1–0.5% w / v 10 polysorbate 80: 0.1–1% w / v poloxamer 407: 1–2% w / v carbopol: 0.1–1% w / v xanthan gum: 0.1–0.5% w / v glycerin: 1–5% w / v 15 citric acid: 0.05–0.1% w / v purified water: q.s. to 100%.

2. A nasal spray pharmaceutical formulation comprising between about 0.40 mg and about 4.8 mg of amoxicillin and 0.05 mg and about 2.1 mg of clavulanate, or a respective salts thereof, in a multi-dose of the nasal spray pharmaceutical 20 formulation.

3. The nasal spray pharmaceutical formulation of claim 1, wherein intranasal administration of a single dose of the nasal spray pharmaceutical formulation to a subject provides amoxicillin clavulanate concentration that is efficacious for eliminating nasal bacterial infections. 25 4. The nasal spray pharmaceutical formulation as claimed in claim 1, wherein the composition has a pH in the range of 5.1 to about 7.1.

5. The nasal spray pharmaceutical formulation as claimed in claim 1, wherein the composition is stable for at least 12 months at 25°C and 60% relative humidity. 5 6. The nasal spray pharmaceutical formulation as claimed in claim 1, wherein the composition is formulated as a nasal spray.

7. The nasal spray pharmaceutical formulation as claimed in claim 1, wherein 10 the intranasal administration of a single dose of the nasal spray pharmaceutical formulation to a subject provides amoxicillin clavulanate concentration that is efficacious for the eliminate nasal bacterial infections.

8. The nasal spray pharmaceutical formulation as claimed in claim 1, wherein a dose of the formulation is about 100 μl. 15 9. The nasal spray pharmaceutical formulation as claimed in claim 1, wherein mucoadhesive polymer chitosan enhances drug retention in the nasal cavity upon administration.

10. The nasal spray pharmaceutical formulation as claimed in claim 1 has a viscosity of 1,000–3,000 cps, ensuring optimal deposition in the nasal cavity. 20 11. The nasal spray pharmaceutical formulation as claimed in claim 1disrupts bacterial biofilms in the sinus cavity through the combined action of amoxicillin, clavulanate, and chitosan.

12. The nasal spray pharmaceutical formulation as claimed in claim 1is dispensed as droplets with a particle size between 10–20 µm, suitable for effective nasal 25 deposition and sinus penetration.

13. The nasal spray pharmaceutical formulation as claimed in claim 1, is an aqueous suspension suitable for targeted drug release at the sinus infection site.

14. The nasal spray pharmaceutical formulation as claimed in claim 1, wherein the inclusion of poloxamer 407 and carbopol enables sustained release of the active pharmaceutical ingredients for a duration of 8 to 24 hours.

15. The nasal spray pharmaceutical formulation as claimed in claim 1, wherein 5 the inclusion of mucoadhesive polymer chitosan increases the residence time of the formulation in the nasal cavity by at least 30% compared to a non- mucoadhesive formulation.

16. The nasal spray pharmaceutical formulation as claimed in claim 1, wherein the combination of amoxicillin, clavulanate, and chitosan disrupts bacterial 10 biofilms by penetrating the biofilm matrix and inhibiting bacterial adhesion within the sinus cavities.

17. The nasal spray pharmaceutical formulation as claimed in claim 1, wherein the dosage is tailored for: Mild Infections: 0.53 mg / 100 µL of amoxicillin and 0.27 mg / 100 µL of 15 clavulanate; Moderate Infections: 0.8 mg / 100 µL of amoxicillin and 0.4 mg / 100 µL of clavulanate; Severe Infections: 1.2 mg / 100 µL of amoxicillin and 0.6 mg / 100 µL of clavulanate. 20 18. A method of treating a post-surgical nasal infection in a human or animal, comprising: (a) providing an aqueous pharmaceutical suspension comprising: (i) about 0.001% w / v to about 4.87% w / v amoxicillin; (ii) about 0.001% w / v to about 2.13% w / v clavulanate; (iii) chitosan; (iv) polyvinyl alcohol; (v) 25 EDTA; (vi) polysorbate 80; (vii) poloxamer 407; (viii) carbopol; (ix) xanthan gum; (x) glycerin; and (xi) citric acid;(b) administering said suspension nasally to the subject in an amount effective to treat the post-surgical nasal infection.

19. The method of claim 18, wherein the post-surgical nasal infection is selected 5 from the group consisting of sinusitis, rhinitis, rhinosinusitis, nasal vestibulitis, furunculosis, and septal abscess.

20. A method for preparing a nasal spray formulation comprising: providing a chitosan solution comprising chitosan dissolved in an aqueous 10 acidic solution; providing a polymer solution comprising polyvinyl alcohol, poloxamer 407, carbopol, and xanthan gum dissolved in water; providing a buffer solution comprising citric acid and EDTA dissolved in water, wherein the pH of the buffer solution is adjusted to between 6.5 and 15 7.5; providing a surfactant solution comprising polysorbate 80 and glycerin dissolved in water; providing an active pharmaceutical ingredient (API) solution comprising amoxicillin and clavulanate potassium dissolved in the polymer solution; 20 combining the chitosan solution, polymer solution, the buffer solution, and the surfactant solution with the API solution; homogenizing the combined solution using a high-shear homogenizer; filtering the homogenized solution through a 0.22 µm sterile filter; andfilling the sterile filtered solution into metered-dose nasal spray devices.

21. Use of the composition of any one of claims 1-20 for the manufacture of a medicament for the treatment of post-surgical nasal infections in a human or 5 animal.

22. A kit comprising: a) a container containing the composition of any one of claims 1-18; and b) instructions for use of the composition. 10 6. DATE AND SIGNATURE15Dated this 29thday of December 2024 Signature (Mr. Srinivas Maddipati) IN / PA 3124 20 Agent for Applicant.

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