Development and Response Surface Optimization of Povidone-Iodine– incorporated PVA and Gelatin Films for Controlled Antimicrobial Drug Delivery and Wound Healing

Kanchan Chaudhari*, Ashish Pawar, Ashwini Dokhale

Pharmaceutics Department, M.G.V's Pharmacy College, Nashik, Maharashtra, India 422003.

*Corresponding Author E-mail: kanchanc1117@gmail.com

ABSTRACT:

In this study, investigation on the formulation, optimization, and detailed characterization of povidone iodine (PVP-I)-incorporated, polyvinyl alcohol (PVA) and gelatine composite films intended for antimicrobial wound dressing applications. Films were prepared by the solvent casting method using citric acid as a crosslinking agent and glycerine as a plasticizer. The effect of PVA (Factor A) and gelatine (Factor B) concentrations on tensile strength (TS) and percent cumulative drug release (%CDR) at 12 hours were evaluated using a two-factor, three-level Central Composite Design (CCD) under Response Surface Methodology (RSM). Thirteen runs were carried out; nine yielded evaluable films. The optimized formulation contained 2.310 g PVA and 0.618 g gelatine, with predicted values of 1.304 MPa tensile strength and 95.09% cumulative drug release (%CDR) at 12 h. The optimized film exhibited a pH of 6.5, thickness of 0.17 mm, folding endurance greater than 300 folds, and tensile strength of 3.15 MPa. A high swelling index (187.87 ± 8.64%) indicated good water absorption capacity. FTIR and DSC studies confirmed the compatibility of PVP-I with the polymer matrix and the absence of significant drug–polymer interactions. In vitro drug release studies established an initial release around 53.5% within 1 h, followed by sustained release reaching about 95% after 12 h. These findings suggest that the developed PVP-I composite film is a promising wound dressing system with suitable mechanical properties and prolonged antimicrobial drug release.

KEYWORDS: Povidone iodine, PVA, Gelatine, Solvent casting, RSM, Tensile strength, DSC, Swelling index.

1. INTRODUCTION:

Wound healing is a compound biological process that repairs the structure and function of damaged tissues after wound.

It occurs through a series of overlapping phases, i.e. haemostasis, inflammation, proliferation, and tissue remodelling, which must be carefully regulated for effective healing¹. Interruptions during any stage of the wound healing process, especially those caused by microbial contamination, can impair tissue repair and result in chronic wounds. These non-healing wounds often cause significant patient discomfort, extend recovery time, and increase the overall burden on healthcare systems². The body's healing response is driven by molecular signals, primarily cytokines and growth factors, which dictate how cells migrate, multiply, and reconstruct blood vessels and tissue structures. Important growth factors involved in tissue repair include epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), transforming growth factor-β (TGF-β), and growth hormone (GH^3,4.

Among these factors, EGF plays a crucial role in wound healing because of its ability to stimulate the proliferation of keratinocytes and fibroblasts, which are essential for tissue regeneration⁵. The combined use of recombinant human EGF and acidic FGF significantly improved wound closure in patients with diabetic foot ulcers⁶. However, the therapeutic use of EGF is limited by its short half-life and rapid degradation at the wound site. To overcome these limitations, researchers have developed several controlled delivery systems, including mucoadhesive films⁷, hyaluronate–EGF conjugates⁸, chitosan-based sustained-release films^9,10, and cationized gelatine hydrogels¹¹. Moreover, GH and its mediator insulin-like growth factor-1 (IGF-1) contribute significantly to tissue regeneration, particularly in chronic wounds and burn injuries¹². These findings highlight the importance of developing advanced wound dressings capable of supporting tissue repair while maintaining the activity of therapeutic agents.

Among the available antiseptics, povidone-iodine (PVP-I) is one of the most widely used because of its broad-spectrum antimicrobial activity. PVP-I is effective against Gram-positive and Gram-negative bacteria, fungi, viruses, protozoa, and bacterial spores, while microbial resistance to iodine has rarely been reported¹³. Also the lower concentrations of PVP-I release free iodine more efficiently and therefore exhibit faster antimicrobial activity than highly concentrated formulations¹⁴. The typical application of 0.5% PVP-I increased TGF-β expression in a rat wound model, resulting in enhanced granulation tissue formation, angiogenesis, and re-epithelialization¹⁵. If the dressings containing both acetic acid and povidone-iodine produced faster reduction of purulent discharge in chronic wounds compared with either treatment alone¹⁶. It was concluded that iodine-based dressings are particularly effective in superficially infected wounds because iodine can easily penetrate the wound surface¹⁷. Though, the therapeutic success of PVP-I depends on maintaining an adequate and sustained release of iodine over time. Therefore, suitable delivery systems are required to ensure prolonged antimicrobial activity at the wound site¹⁸.

Polymer films improve wound care by blocking contaminants, locking in moisture, and providing a steady, controllable release of medicine a process dictated by the film's specific structural design¹⁹. Studies repeatedly highlight the success of these films, particularly those using PVP-I. Previous studies consistently show that adding PVP-I to polymer dressings such as alginate or PVA-HPMC films successfully fights infections, lowers inflammation, and reduces scarring compared to traditional bandages^19,20,21. Though, there is a noticeable gap in the research regarding PVA-gelatine films crosslinked with citric acid for PVP-I delivery.

Citric acid acts as a safe, non-toxic binder that boosts the film's strength, stability, and drug release capabilities. Glycerine is incorporated as a plasticizer to enhance flexibility and prevent brittleness during handling. The combination of PVA, gelatine, citric acid, and glycerine provides a versatile matrix capable of controlling water uptake, swelling behaviour, and drug diffusion while maintaining adequate mechanical integrity^2,18. Fibroblast growth factor-2 into fucoidan/chitosan multilayer systems to promote tissue regeneration²². A chitosan-based injectable hydrogel with antibacterial and haemostatic properties²³, while alginate/chitosan films containing aloe Vera and silver nanoparticles for enhanced antimicrobial activity²⁴. Prepared sodium alginate films loaded with antimicrobial essential oils for wound dressing applications²⁵. These studies demonstrate that the composition of the polymer matrix strongly influences the physicochemical and biological performance of wound dressings, highlighting the need for systematic optimization of formulation variables.

Response Surface Methodology (RSM) combined with Central Composite Design (CCD) is a powerful statistical tool used for formulation optimization. This approach enables simultaneous evaluation of multiple formulation variables and their interactions while minimizing the number of experimental trials required. Based on the above considerations, the present study aimed to develop and optimize povidone-iodine-loaded PVA/gelatine films using the solvent casting technique. The concentrations of PVA, gelatine, glycerine, and citric acid were systematically varied and optimized using CCD-RSM to obtain films with desirable tensile strength and sustained drug release. Drug–excipient compatibility was investigated using Fourier-transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). The prepared films were further evaluated for thickness, weight uniformity, folding endurance, surface pH, swelling behaviour, and in vitro drug release characteristics. The findings of this study may contribute to the development of effective antimicrobial wound dressings capable of providing sustained povidone-iodine release and improved wound healing performance.

2. MATERIALS AND METHODS:

2.1 Materials:

Povidone-iodine (PVP-I, 10% available iodine) was used as the active drug. Polyvinyl alcohol (PVA, 6–9% w/v) and gelatine (Type A, 3–5% w/v) were used as film-forming polymers. Citric acid (2–4% w/v) was used as a crosslinking agent, and glycerine (2–4% v/v) was used as a plasticizer. Sodium thiosulfate (0.1 M), starch, phosphate buffer (pH 7.4), and purified water were used for analysis and evaluation studies. Muslin cloth and 10 cm Teflon Petri dishes were used during film preparation. The composition of the prepared PVA, gelatine and PVP-I films is presented in Table 1.

Table 1. Composition of fabricated PVA, Gelatine and PVP-I films

Ingredient	Concentration	Function
PVA (dissolved hot)	6–9% w/v	Primary film-forming polymer
Gelatine	3–5% w/v	Secondary polymer/ bioactive protein
Povidone Iodine (PVP-I)	5% w/w	Active antimicrobial drug
Glycerine	2–4% v/v	Plasticizer
Citric Acid (anhydrous)	2–4% w/v	Crosslinking agent
Purified Water	q.s. to 25 mL	Solvent

2.2 Film Preparation by Solvent Casting

PVA was dissolved in purified water at 80–90°C with continuous stirring until clear. Cooled to 50°C, gelatine added and stirred until dissolved. Citric acid added, stirred 15–30min. Glycerine added, then PVP-I (5% w/w), and stirred thoroughly. Sonicated 10–15min to remove air bubbles. Filtered through muslin cloth. 25 mL aliquots poured into Teflon Petri dishes and dried below 45°C to constant weight. Films peeled and stored in polyethylene pouches.

2.3 Central Composite Design (CCD):

A two-factor, three-level CCD was prepared using Design-Expert tool. Factor A = PVA (g/25mL); Factor B = Gelatine (g/25mL). Responses: R1 = tensile strength (MPa); R2 = %CDR at 12 h. Model: Y = β₀ + β₁A + β₂B + β₁₂AB + β₁₁A² + β₂₂B². Table 2 represent CCD experimental runs with responses. Films 2, 7, 9, and 12 were excluded from further evaluation because Film 2 was fragile and brittle due to insufficient PVA content, whereas Films 7, 9, and 12 exhibited rigid and non-pliable characteristics as a result of excessive gelatine content (≥ 1.2 g). (Table-2).

2.4 Drug Analysis and Calibration:

The iodine content of PVP-I was determined using titrimetric and UV spectrophotometric methods. For the titrimetric method, 0.1M Na₂S₂O₃ solution was prepared by dissolving 25g Na₂S₂O₃ and 0.2g Na₂CO₃ in CO₂ free water and making the volume up to 1L. A 3g sample of PVP-I was dissolved in 200 mL of water at room temperature and analyzed within 1h. The solution was titrated immediately with 0.1M Na₂S₂O₃ using 3 mL starch indicator. In this method, 1 mL of 0.1 M Na₂S₂O₃ was equivalent to 0.01269g of iodine (I).

For the UV spectrophotometric method, 100mg of PVP-I was dissolved in a 100mL stoppered iodine flask and diluted to volume to obtain a stock solution of 1000 µg/mL. The λmax was found at 290nm by scanning the solution over the range of 250–600nm using a concentration of 750µg/mL. A calibration curve for drug release studies was prepared in PBS (pH 7.4) using concentrations ranging from 150–450µg/mL. PVP-I calibration curve data is as shown in Table 3 with the equation of curve.

Table 2. CCD experimental runs with responses

Run	PVA (g)	Gelatine (g)	Film formed?	TS (MPa)	%CDR (12h)
Film 1	1.8	0.9	Yes	0.98	78.55
Film 2	0.951	0.9	Failed	—	—
Film 3	1.8	0.9	Yes	0.79	78.39
Film 4	2.64	0.9	Yes	0.796	76.47
Film 5	1.8	0.9	Yes	0.309	86.66
Film 6	1.8	0.9	Yes	1.02	90.06
Film 7	1.8	1.32	Failed	—	—
Film 8	1.8	0.9	Yes	0.404	90.07
Film 9	1.2	1.2	Failed	—	—
Film 10	2.4	0.6	Yes	1.38	71.41
Film 11	1.8	0.474	Yes	0.934	89.51
Film 12	1.8	1.2	Failed	—	—
Film 13	1.2	0.6	Yes	0.531	94.2

Table 3. PVP-I calibration curve data

Sr. No.	Conc. (µg/mL)	Absorbance (290 nm)	Equation
1	150	0.077	y = 0.144x − 0.1624 R² = 0.9333
2	200	0.148
3	250	0.195
4	300	0.338
5	350	0.455
6	400	0.745
7	450	0.936

Figure 1. Calibration curve of PVP-I at 290 nm in PBS pH 7.4

The Figure 1 shows that Calibration curve of povidone iodine in phosphate buffer pH 7.4 at λ_max290nm. Working concentrations: 150–450 µg/mL. Regression: y = 0.144x − 0.1624, R² = 0.9333. Dashed line = regression fit.

2.5 Characterization Methods

The prepared films were assessed for their physicochemical properties as the details are mentioned below.

a) pH: The pH was determined by dissolving the film in 10 mL of purified water and measuring the pH in triplicate using a calibrated digital pH meter.

b) Film thickness: Film thickness was measured at five different locations using a digital micrometer with an accuracy of ±0.001 mm.

c) Folding endurance: Folding endurance was assessed by repeatedly folding a 2 × 2 cm film sample at the same point until visible cracks appeared.

d) Tensile strength: Tensile strength was measured using a texture analyser and calculated as the ratio of the maximum applied force to the cross-sectional area of the film. The force was obtained from the peak load and converted to Newton’s.

e) Swelling index: The swelling behaviour was evaluated by immersing a 2 × 2 cm film sample in PBS (pH 7.4), and the swelling index was calculated from the percentage increase in film weight. All measurements were performed in triplicate using the optimized film formulation.

f) DSC: Thermal analysis was carried out using a Mettler Toledo DSC 3 instrument under a nitrogen atmosphere (50mL/min). Samples were heated from 30 to 300°C at a heating rate of 10°C/min in a 40µL aluminum pan, and the thermograms were recorded using STARe SW V16.40 software.

2.6 In Vitro Drug Release

One film of 2*2 cm is added in 250 mL conical flask with 50 mL PBS pH 7.4; 37.5 ± 0.5°C; 50 rpm. Sampling at 1, 2, 3, 4, 5, 6, 12 h; 3 mL withdrawn and replaced with fresh PBS. UV 290 nm; CDR (mg) calculated cumulatively with DF correction.

3. RESULTS AND DISCUSSION:

3.1 Film Preparation

From the 13 formulations prepared using the Central Composite Design (CCD), nine films were successfully achieved and selected for further assessment. Film 2, containing 0.951 g of PVA, was brittle and fragile, indicating that the polymer amount was insufficient to form a stable film matrix. Films 7, 9, and 12, which contained gelatine at levels of 1.2 g or higher, produced rigid and non-flexible films due to the high polymer content. The remaining nine films showed good physical appearance, with smooth surfaces, adequate flexibility, and transparency ranging from clear to slightly amber. The yellowish-brown coloration was recognised to the presence of the PVP-I–iodine complex within the film matrix.

3.2 Response Surface Methodology- Tensile Strength

As represented in Table 4, the quadratic model was found to be statistically significant with values F = 9.22, p = 0.0055, representing a good relationship between the formulation variables and the response. The model showed an R² value of 0.8682, suggesting that about 87% of the variation in the response was explained by the model. The predicted R² (0.7499) was in good agreement with the adjusted R² (0.7741), confirming the model's reliability. An adequate precision value of 9.461 (>4) indicated a satisfactory signal-to-noise ratio. The lack-of-fit test was not significant (F = 0.09, p = 0.9641), demonstrating a good fit of the model to the experimental data. Among the model terms, PVA, gelatine, and their interaction (AB) showed significant effects on the response (p < 0.05). Positive linear coefficients for A and B show that individually increasing either polymer improves Tensile Strength. The negative AB coefficient shows that simultaneously exceeding optimal balance reduces strength (competitive chain interactions, inhomogeneous crosslinking). Table 4 shows ANOVA for Tensile Strength (MPa).

Table 4. ANOVA for Tensile Strength (MPa)

Source	SS	df	MS	F-value	p-value	Remarks
Model	2.40	5	0.4809	9.22	0.0055	Significant
A – PVA	0.7765	1	0.7765	14.89	0.0062
B – Gelatine	0.9208	1	0.9208	17.66	0.0040
AB interaction	0.4670	1	0.4670	8.96	0.0201
A² (quadratic)	0.1683	1	0.1683	3.23	0.1154	NS
B² (quadratic)	0.1019	1	0.1019	1.96	0.2047	NS
Residual	0.3649	7	0.0521	—	—
Lack of Fit	0.0221	3	0.0074	0.09	0.9641	Not Sig. ✓
Pure Error	0.3428	4	0.0857	—	—
Cor Total	2.77	12	—	—	—

Table 5. ANOVA for %CDR

Source	SS	df	MS	F-value	p-value	Remarks
Model	17626.12	5	3525.22	17.96	0.0007	Significant
A – PVA	3256.25	1	3256.25	16.59	0.0047
B – Gelatine	5765.50	1	5765.50	29.37	0.0010
AB interaction	726.84	1	726.84	3.70	0.0957	NS
A² (quadratic)	5017.45	1	5017.45	25.56	0.0015
B² (quadratic)	3876.56	1	3876.56	19.75	0.0030
Residual	1374.09	7	196.30	—	—
Lack of Fit	1253.29	3	417.76	13.83	0.0141	Significant
Pure Error	120.80	4	30.20	—	—
Cor Total	19000.21	12	—	—	—

The regression equation for tensile strength is as presented in equation 1.

Tensile Strength (MPa) = −4.814 + 3.783(PVA) + 4.707(Gelatine) − 1.898(PVA× Gelatine) − 0.432(PVA²) − 1.345(Gelatin²) …..(1)

The 3D response surface as shown in Figure 2 exhibited a monotonically ascending topology, confirming that tensile strength increased progressively with rising PVA (A) and gelatine (B) concentrations. The contour plot showed a steady increase in tensile strength from about 0.2 MPa indicated by blue region to 1.3 MPa indicated by red-orange region, with increasing amounts of both PVA and gelatine. This trend confirms that both polymers had a significant positive effect on tensile strength. The curved contour pattern indicated a significant interaction between PVA and gelatine, suggesting that their combined effect improved the strength of the film matrix. Since the quadratic terms were not significant, no optimum peak tensile strength was observed within the studied formulation range.

Figure 2. Model 3D surface graph for tensile strength

3.3 Response Surface Methodology- Percent Drug Release

As shown in Table 5, the ANOVA results showed that the model for %CDR at 12 h was significant (F = 17.96, p = 0.0007) and explained 92.8% of the response variability (R² = 0.9277). The adequate precision value of 10.003 confirmed a satisfactory model signal. However, a significant lack of fit was observed, likely due to variation among the centre-point formulations. PVA, gelatine, and their quadratic effects (A² and B²) significantly influenced the drug release profile (p < 0.05). Positive linear coefficients for A and B; strong negative quadratic coefficients indicate drug release peaks at intermediate concentrations then falls high polymer concentration creates denser crosslinked barrier restricting drug diffusion.

The regression equation for tensile strength is as presented in equation 2.

%CDR = −473.27 + 369.59(PVA) + 517.44(Gelatine) − 74.89(PVA× Gelatine) − 74.60(PVA²) − 262.29(Gelatin²) ……(2)

The 3D response surface as shown in Figure 3, displayed a well-defined concave dome profile, with a distinct central maximum with red apex and %CDR approximately 90–95% descending steeply toward both extremes of the design space. The inverted paraboloid shape of the response surface indicated that drug release increased up to an optimum polymer concentration and then decreased at higher levels of PVA and gelatine. This behaviour suggests that excessive polymer content formed a denser film matrix, which acted as a stronger diffusion barrier and slowed the release of PVP-I from the film. The concentric elliptical contours delineated a well-defined optimal response region, within which the selected formulation (PVA = 2.310 g, gelatine = 0.618 g; predicted %CDR = 95.094%) resided, confirming the validity of the desirability-based numerical optimization.

Figure 3. Model 3D surface Graph for %CDR

3.4 Numerical Optimization

For optimization, PVA and gelatine concentrations were varied within the ranges of 1.5–2.4 g and 0.6–0.9 g, respectively, while aiming to maximize tensile strength and %CDR. The Design-Expert software generated 45 solutions, all with a desirability value of 1.000. Among these, Solution 4 was selected as the optimized formulation, containing 2.310 g of PVA and 0.618 g of gelatine. This formulation showed predicted values of 1.304 MPa tensile strength and 95.094% cumulative drug release at 12 h. Table 6 shows the top 5 optimization solutions. (Table-6).

3.5 Physicochemical Characterization

Table 7 presented complete physicochemical characterization of all film batches.

pH (5.27–6.69): All films fell within the wound-compatible range (~5.5–7.0). The optimised batch pH ≈ 6.5. The slightly acidic character reflects citric acid cross linker and iodine species from PVP-I; a mildly acidic environment supports antimicrobial activity.

Thickness (0.15–0.22 mm): Higher total polymer content produces thicker films when casting the same 25 mL volume. Optimised film = 0.17 mm.

Folding endurance: All films >300 folds without cracking excellent flexibility conferred by glycerine plasticization and inherent PVA ductility.

Tensile strength: Film 10 (PVA 2.4 g, gelatine 0.6 g) had the highest TS among the formulation runs (1.38 MPa), consistent with RSM predictions. Optimised batch experimental TS = 3.15 MPa (peak load 481 g, width 15.00 mm, depth 0.10 mm; F = 4.72 N, A = 1.5 mm²).

Figure 4. Tensile strength of all film batches

Tensile strength for all 9 evaluated batches and the optimised batch as shown in Figure 4. Optimised batch TS = 3.15 MPa (peak load 481 g, width 15 mm, depth 0.10 mm). Film 10 shows the highest TS (1.38 MPa) among the CCD batches.

Table 6. Top 5 optimization solutions

No.	PVA (g)	Gelatine (g)	Pred. TS (MPa)	Pred. %CDR	Desirability
1	2.324	0.624	1.305	94.888	1.000
2	2.400	0.600	1.383	92.238	1.000
3	2.339	0.614	1.328	94.336	1.000
4 ◀	2.310	0.618	1.304	95.094	1.000
5	2.381	0.616	1.349	93.153	1.000

Table 7. Complete physicochemical characterization of all film batches

Batch	PVA(g)	Gel(g)	Thick.(mm)	pH	TS(MPa)	%CDR(12h)	Folding
Film 1	1.800	0.900	0.18	5.67	0.980	78.55	>300
Film 3	1.800	0.900	0.19	5.51	0.790	78.39	>300
Film 4	2.640	0.900	0.21	5.50	0.796	76.47	>300
Film 5	1.800	0.900	0.15	5.70	0.309	86.66	>300
Film 6	1.800	0.900	0.16	6.10	1.020	90.06	>300
Film 8	1.800	0.900	0.18	6.09	0.404	90.07	>300
Film 10	2.400	0.600	0.19	5.27	1.380	71.41	>300
Film 11	1.800	0.474	0.21	6.69	0.934	89.51	>300
Film 13	1.200	0.600	0.22	5.91	0.531	94.20	>300
Optimised	2.310	0.618	0.17	6.50	3.150	94.89	>300

Figure 5. pH and thickness comparison across all film batches

Figure 5 represent the pH (blue bars, left axis) and film thickness in mm (red bars, right axis) for all 9 evaluated batches and the optimised film. pH range: 5.27–6.69; thickness range: 0.15–0.22mm.

3.6 Swelling Index

Table 8 presents the swelling index of the optimized PVP-I film in PBS (pH 7.4). The film exhibited gradual water uptake upon immersion, indicating its ability to absorb the surrounding medium and swell. This swelling behaviour is important for maintaining film integrity and supporting the controlled release of PVP-I from the polymer matrix.

Table 8. Swelling index of the optimised PVP-I film (PBS pH 7.4)

Trial	W₀ (g)	Wt (g)	SI (%)	Calculation
1	0.146	0.412	182.1	[(0.412−0.146)/0.146]×100
2	0.154	0.437	183.7	[(0.437−0.154)/0.154]×100
3	0.140	0.417	197.8	[(0.417−0.140)/0.140]×100
Mean ± SD			187.87 ± 8.64%

SI = [(Wt − W₀)/W₀] × 100.

The data presented in Table 8 and Figure 6 showed that the optimized PVP-I film exhibited a high swelling index of approximately 188%. This high swelling behaviour can be attributed to the hydrophilic nature of the PVA/gelatine matrix, which readily absorbs water and expands upon contact with the medium. On contact with wound exudate, the film swells and forms a hydrogel-like structure that absorbs exudate and maintains a moist wound environment while slowly releasing PVP-I. Structural integrity was maintained (film did not disintegrate), confirming adequate crosslinking by citric acid.

Figure 6. Swelling index of the optimised film in PBS pH 7.4. Trials 1–3: 182.1%, 183.7%, 197.8%. Mean ± SD = 187.87± 8.64% (orange dashed line).

3.7 Differential Scanning Calorimetry (DSC):

The Figure 7 Shows that small, low-enthalpy endothermic peak at 62.13°C is consistent with minor dehydration or conformational relaxation in hygroscopic PVP-based materials not a classical melting event. The Tg confirms PVP-I is amorphous, which favours intimate drug polymer mixing and uniform drug distribution within the film matrix. The stable baseline from ~110–250°C (no new peaks) confirms the absence of drug–polymer incompatibility in this thermally significant region.

Figure 7. DSC Thermograph of pure PVP-I

The DSC thermograph of the film formulation (2.6000 mg) revealed two thermal events as shown in Figure 8. A glass transition was observed at an onset temperature of 126.89 °C with a midpoint of 114.44 °C, suggesting the presence of an amorphous polymeric component in the film. Additionally, a broad endothermic peak was recorded with an onset at 182.95 °C and a peak maximum at 193.73 °C, having an enthalpy value of −5.87 J·g⁻¹. This endothermic transition corresponds to the melting of the drug or excipient present in the formulation, confirming the thermal stability and physical compatibility of the film components.

Figure 8. DSC Thermograph of formulation (Film)

3.8 Fourier Transform Infrared Spectroscopy (FTIR):

3.8.1 FTIR Spectra for Povidone Iodine (PVP-I):

The Figure 9 represented infrared spectra of povidone iodine (PVP-I), it shows that characteristic absorption bands corresponding to the functional groups present in the sample. The broad peak at 3406 cm⁻¹ indicates O–H stretching, while the band at 2950 cm⁻¹ is attributed to aliphatic C–H stretching. The strong absorption at 1638 cm⁻¹ corresponds to C=O stretching. Peaks observed between 1491–1420 cm⁻¹ are associated with C–H bending vibrations, whereas bands in the range of 1284–1014 cm⁻¹ are related to C–O and C–O–C stretching. The peaks below 1000 cm⁻¹ represent out-of-plane C–H bending vibrations. These results confirm the presence of the expected functional groups in the sample.

Figure 9. FTIR Spectra for PVP-I

3.8.2 FTIR Spectra for Physical mixture:

The FTIR spectra shown in Figure 10 evaluated broad O–H stretching band at 3169 cm⁻¹ and C–H stretching peaks at 3048 and 2949 cm⁻¹. The characteristic peak at 1735 cm⁻¹ indicates C=O stretching, while the band at 1652 cm⁻¹ is associated with carbonyl-related vibrations. Peaks in the range of 1493–1009 cm⁻¹ correspond to C–H bending and C–O/C–O–C stretching vibrations. The bands at 845, 739, and 692 cm⁻¹ are attributed to out-of-plane bending vibrations, confirming the presence of the expected functional groups in the sample.

Figure 10. FTIR Spectra for Physical mixture

From the FTIR spectra of both Povidone iodine-I and Physical mixture revealed similar characteristic peaks corresponding to O–H, C–H, C=O, C–O, and C–O–C functional groups. The absence of major peak shifts or disappearance of characteristic bands indicates good compatibility among the formulation components and confirms the successful combination of the materials without significant chemical interaction.

3.9 In Vitro Drug Release:

Table 9 presents the complete cumulative drug release (%CDR) profile of the optimized PVP-I film over the study period. The results show the percentage of drug released at different time intervals, providing information on the release behaviour and sustained delivery of PVP-I from the film matrix.

Figure 11 shows the in vitro drug release profiles (%CDR) of all PVP-I film formulations in PBS (pH 7.4) at 37.5 ± 0.5°C and 50 rpm over 12 h, monitored at 290 nm. The results demonstrate the drug release behaviour of the different film batches.

Table 9. Complete %CDR time-course data

Time(h)	Film1	Film3	Film4	Film5	Film8	Film10	Film11	Film13	Optimized
1	53.51	53.51	53.51	53.51	53.51	53.51	53.51	53.51	53.51
2	56.68	56.87	56.44	58.57	58.01	56.66	58.38	58.75	59.19
3	63.51	63.33	60.36	66.17	62.85	59.84	63.70	64.29	64.99
4	67.69	67.43	64.22	72.16	67.76	63.16	68.39	70.16	70.86
5	71.60	71.71	68.54	78.18	72.19	66.02	72.82	75.59	76.29
6	75.66	75.66	72.46	82.79	76.70	68.96	77.03	80.57	81.27
12	78.54	78.39	76.47	86.67	90.07	71.41	89.51	94.20	94.90

Figure 11. In vitro drug release profiles (%CDR) for all PVP-I film batches in PBS pH 7.4

Figure 12. Final %CDR at 12 hours for all batches

As shown in Figure 12, all film formulations exhibited a biphasic drug release pattern, with approximately 53.5% of PVP-I released within the first hour, indicating a similar amount of drug present near the film surface. Drug release gradually increased over time, reaching 71.4–94.2% after 12 h. Film 10, containing the highest PVA concentration (2.4 g), showed the lowest drug release (71.41%), likely due to the formation of a denser polymer matrix that restricted drug diffusion. In contrast, Film 13 and the optimized formulation achieved the highest release, reaching approximately 94% cumulative drug release at 12 h. The biphasic sustained release is ideal for wound dressings: the initial burst provides rapid antimicrobial coverage and the sustained phase maintains therapeutic iodine concentrations throughout the dressing-change interval.

4. CONCLUSION:

PVP-I incorporated PVA and gelatine composite films were successfully developed by the solvent-casting method and optimized using a CCD). Out of 13 experimental formulations, 9 films showed acceptable physical properties, while four formulations failed due to either insufficient PVA content or excessive gelatine concentration.

RSM demonstrated that both PVA and gelatine significantly influenced tensile strength and drug release behaviour. The tensile strength model was statistically significant (F = 9.22, p = 0.0055, R² = 0.8682), whereas the %CDR model showed an even stronger fit (F = 17.96, p = 0.0007, R² = 0.9277). Numerical optimization generated 45 acceptable solutions, and the optimized formulation containing 2.310 g PVA and 0.618 g gelatine was selected with predicted values of 1.304 MPa tensile strength and 95.09% cumulative drug release at 12 h.

The optimized film revealed required physicochemical characteristics, including pH 6.5, thickness 0.17 mm, and folding endurance greater than 300 folds, confirming its suitability for wound application. The experimentally determined tensile strength reached 3.15 MPa, indicating excellent mechanical integrity. The film also showed a high swelling index (187.87 ± 8.64%) in PBS (pH 7.4), representing its capability to absorb wound exudate while maintaining structural stability.

FTIR analysis confirmed the presence of characteristic functional groups without significant peak shifts, indicating good compatibility between PVP-I and the polymer matrix. DSC analysis revealed the amorphous nature of PVP-I and the absence of drug–polymer incompatibility within the studied temperature range.

In vitro release studies revealed a desirable biphasic release pattern, with approximately 53.5% drug release within 1 h followed by sustained release up to 94.2% after 12 h. The optimized formulation achieved nearly 95% cumulative drug release, ensuring extended availability of iodine at the application site.

It is observed that, the optimized PVP-I incorporated PVA and gelatine composite film combined shows the excellent mechanical strength, high swelling capacity, physicochemical stability, and sustained drug release.

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Received on 05.01.2026 Revised on 08.04.2026

Accepted on 10.06.2026 Published on 01.07.2026

Available online from July 04, 2026

Research J. Pharmacy and Technology. 2026;19(7):3365-3374.

DOI: 10.52711/0974-360X.2026.00478

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