INTRODUCTION:

The therapeutic potential of several antifungal agents has been considerably hindered due to limitations in oral bioavailability, primarily attributed to poor aqueous solubility. Among these, ketoconazole has been recognized as a clinically important imidazole antifungal compound, yet its widespread application in systemic infections such as candidiasis, blastomycosis, and dermatophytosis has been restricted owing to inconsistent absorption and its requirement for an acidic gastric environment.

Ketoconazole has been categorized under the Biopharmaceutics Classification System (BCS) Class II, as it exhibits high permeability but low aqueous solubility, making dissolution the rate-limiting step in its gastrointestinal absorption.¹ A melting point of approximately 146°C and a half-life of 3.3 hr have been reported.² Furthermore, its solubility has been shown to decrease significantly, when administered concomitantly with antacids or acid-reducing agents, leading to diminished bioavailability and inter-patient variability.^3,4 These factors present notable formulation challenges and necessitate the application of advanced drug delivery strategies aimed at enhancing dissolution and improving systemic availability. Several formulation approaches have been explored to address the poor solubility of BCS Class II drugs, including salt formation, micronization, complexation, use of surfactants, pH modulation, and prodrug synthesis. However, many of these techniques are accompanied by intrinsic limitations. Salt formation may not apply to weakly basic or neutral compounds; micronization, while increasing surface area, may not sufficiently improve wettability; and prodrug approaches often involve extensive chemical modification and regulatory complexity.⁵

To overcome these limitations, the solid dispersion (SD) technique has been widely adopted, especially for poorly soluble drugs. In this technique, the drug is molecularly dispersed within a hydrophilic polymeric matrix, which leads to improved wettability, enhanced surface area, reduced crystallinity, and often the conversion of the drug into a higher-energy amorphous form all contributing to improved solubility and dissolution.⁶

In recent pharmaceutical research, polymers such as Poloxamer 188, Polyethylene Glycol 4000 (PEG 4000), and Polyethylene Glycol 6000 (PEG 6000) have been frequently employed as carriers in the development of solid dispersions. Poloxamer 188 is valued for its surfactant properties, thermoplastic, and biocompatibility, while PEGs have been utilized for their hydrophilic nature, solubilizing capacity, and thermal processing flexibility.^7–9 However, limited comparative data are available on the performance of these specific carriers in ketoconazole-loaded solid dispersion systems, particularly when prepared using both melt fusion and solvent evaporation techniques. This research has been undertaken to bridge this gap by systematically evaluating the effect of different polymeric carriers and processing methods on the physicochemical properties and dissolution behavior of ketoconazole solid dispersions. The influence of carrier selection and method of preparation on drug–excipient interactions, crystallinity, and in-vitro dissolution has been specifically investigated.

Accordingly, this study was designed to formulate solid dispersions of ketoconazole using three different hydrophilic carriers Poloxamer 188, PEG 4000, and PEG 6000 by employing both melt fusion and solvent evaporation techniques. The prepared formulations were subjected to detailed physicochemical characterization using analytical tools such as Fourier Transform Infrared Spectroscopy (FTIR), X-ray Diffraction (XRD), and Differential Scanning Calorimetry (DSC) in order to investigate potential drug–polymer interactions and changes in crystallinity. Furthermore, in-vitro dissolution studies were conducted to evaluate and compare the performance of the developed formulations with pure ketoconazole and a marketed tablet formulation. Through this comprehensive approach, it was intended to identify the most effective carrier and preparation method capable of significantly enhancing the dissolution rate and, consequently, the oral bioavailability of ketoconazole. The findings from this study are expected to contribute valuable insights toward the development of improved oral formulations for BCS Class II drugs.

METHODS AND MATERIALS:

Materials:

Ketoconazole was obtained from Piramal Pharma Ltd., Poloxamer 188, PEG 4000, and PEG 6000. All other chemicals and reagents used were of analytical grade.

Melting Point Determination:

The melting point of Ketoconazole was determined using the capillary method with a standard melting point apparatus. The loaded capillary was then fixed to the apparatus alongside a calibrated thermometer to ensure accurate temperature readings. The temperature was gradually increased at a controlled rate, and the point at which the drug began to melt and completely liquefied was observed. The corresponding temperature range was recorded as the melting point of Ketoconazole.¹⁰

Preparation of Binary and Tertiary SDs:

Binary and ternary solid dispersions (SDs) of ketoconazole (KET) were prepared with different hydrophilic polymeric carriers PEG 4000, Poloxamer 188, and PEG 6000 at various weight ratios as detailed in Table 1. The physical mixtures (PMs) were prepared by gently triturating the drug and polymer(s) in a mortar for one hour to ensure preliminary homogeneity. These mixtures were subsequently dried in a hot air oven maintained at 37°C to eliminate any residual moisture.

Secondary solid dispersions comprising KET and PEG 4000 at drug-to-polymer ratios of 2:1 (SD2:1), 3:1 (SD3:1), 1:4 (SD1:4), and 4:1 (SD4:1) were formulated using the melt fusion method. In this process, both KET and PEG 4000, used in solid form, were first triturated separately to achieve fine powder consistency. The weighed components were then combined and transferred into a standard laboratory porcelain dish. The mixture was heated on a calibrated hot plate set between 120°C and 150°C, with continuous stirring to facilitate uniform melting. Due to the solid-state nature of both substances, complete mixing was observed only during the fusion stage. The molten mass was immediately transferred to an ice bath under constant agitation to ensure rapid solidification and uniform structure. Once solidified, the masses were pulverized using a mortar and pestle, passed through a 100-mesh sieve, and stored in a desiccator over fused calcium chloride to prevent moisture uptake.

Ternary solid dispersions involving KET, Poloxamer 188, and PEG 6000 in drug-to-polymer ratios of 1:2:1 (SD121), 1:1:2 (SD112), 2:1:1 (SD211), 2:2:1 (SD221), 3:2:1 (SD321), and 3:3:1 (SD331) were prepared by the solvent evaporation method. For each formulation, approximately 5 mL of methanol was used to dissolve the individual components. The drug and polymer solutions were mixed thoroughly to obtain a homogeneous solution. This solution was then subjected to solvent removal in a vacuum oven maintained at a temperature range of 50°C to 80°C for 24 hours. The oven conditions were held constant throughout the process to ensure reproducibility. Complete evaporation of methanol was confirmed by observing the absence of solvent odor and ensuring no residual liquid was visible on the container surface. These preparation techniques were employed to investigate the influence of polymer type, drug-to-polymer ratio, and manufacturing method on the physicochemical characteristics and dissolution behavior of ketoconazole. ^11-15

Table 1. Different Formulation Ratios of Solid Dispersion

SD	Formulation	KET	PEG 4000	Poloxamer 188	PEG 6000
Binary	SD12	1	2	-	-
	SD21	2	1	-	-
	SD31	3	1	-	-
	SD14	1	4	-	-
	SD41	4	1	-	-
Tertiary	SD112	1	-	1	2
	SD122	1	-	2	1
	SD211	2	-	1	1
	SD221	2	-	2	1
	SD321	3	-	2	1

Grinding Method (PM):

Physical mixtures of ketoconazole (KET), Poloxamer 188, PEG 4000, and PEG 6000 were prepared by accurately weighing the required quantities of each component based on the predetermined solid dispersion (SD) ratios. The components were manually triturated using a granite-type agate mortar and pestle to ensure homogeneity. The grinding was performed manually for a duration of 15 mins, a time frame optimized through preliminary trials to ensure adequate blending without inducing thermal degradation or polymorphic transitions. The resultant mixtures were passed through a standard 80-mesh sieve to achieve uniform particle size and eliminate agglomerates. Although a complete particle size distribution analysis was not conducted, sieving ensured that all components were reduced to a relatively fine and consistent particle size, appropriate for further processing.^16-18 The processed mixtures were then stored in airtight containers placed in a desiccator at ambient room temperature to prevent moisture uptake and preserve sample integrity until further use.

Solubility Analysis:

A saturation solubility study was conducted to determine the equilibrium solubility of ketoconazole (KET) in different buffer systems. Accurately weighed samples of 100mg KET were introduced into two separate 50 mL glass beakers, each containing 25mL of dissolution medium simulated gastric fluid (pH 1.2, hydrochloric acid buffer) and simulated intestinal fluid (pH 6.8, phosphate buffer composed of 0.05M potassium dihydrogen phosphate adjusted to pH 6.8 using sodium hydroxide). Each condition was prepared in triplicate to ensure reproducibility. The beakers were placed in a metabolic shaker operating at room temperature (approximately 25°C) and agitated continuously for 24 hr to allow adequate time for dissolution equilibrium to be reached. Although the equilibrium solubility was observed to be visually attained within the first hour, the duration was extended to 24 hr to ensure complete saturation. This was confirmed by the presence of undissolved drug particles in the solution, visible to the naked eye, indicating a state of saturation. Following incubation, each sample was sonicated for 30 minutes at room temperature to enhance drug dispersion and dislodge loosely adhered particles. The mixtures were then filtered using Whatman No. 1 filter paper to remove undissolved solids. The filtrates were analysed for ketoconazole content using a UV-Visible spectrophotometer (λmax = 224nm), and the absorbance values were recorded to determine the concentration of dissolved drug in each medium.^19-22

Preparation of Standard Calibration Curve of Ketoconazole in 0.1 N HCl:

To construct a standard calibration curve for the quantification of ketoconazole (KET), a primary stock solution was initially prepared. Precisely 10mg of KET was weighed using an analytical balance and transferred into a volumetric flask. The drug was then dissolved in 10mL of 0.1N hydrochloric acid (HCl) to obtain a concentration of 1mg/mL (1000µg/mL). From this primary solution, 1mL was further diluted to 10mL with 0.1 N HCl to yield a secondary stock solution of 100 µg/mL. From the secondary stock, aliquots of 0.5mL, 1.0mL, 1.5mL, 2.0mL, and 2.5mL were pipetted into separate 10mL volumetric flasks and the volume was made up to the mark with 0.1 N HCl, resulting in final concentrations of 5, 10, 15, 20, and 25µg/mL, respectively. Each solution was thoroughly mixed to ensure uniformity. The absorbance of each prepared standard solution was measured at λmax 224nm using a UV-Visible spectrophotometer, with 0.1 N HCl as the blank. All measurements were performed in triplicate to ensure accuracy and reproducibility. The use of 0.1 N HCl as the solvent for the calibration curve was selected based on the favourable solubility profile of KET in acidic environments, which correlates with its optimal dissolution in gastric pH. This condition mimics the in vivo gastrointestinal environment, which is pharmacologically relevant for oral drug absorption. Additionally, preliminary studies confirmed that phosphate buffer (pH 6.8) failed to solubilize ketoconazole adequately, thereby rendering it unsuitable for preparing calibration standards within the required analytical range. The calibration curve showed good linearity across the studied range (5–25µg/mL), validating its appropriateness for subsequent quantitative analysis of KET in solubility and dissolution studies.^2,15

Fourier Transform Infrared (FT-IR) Spectroscopy:

Fourier Transform Infrared (FTIR) spectroscopy was performed to investigate potential chemical interactions between ketoconazole (KET) and the excipients in physical mixtures (PMs) and solid dispersions (SDs). The analysis was conducted using a Bruker ALPHA II FTIR spectrophotometer. Spectra were recorded over the range of 4000–600 cm⁻¹, with a resolution of 5 cm⁻¹, and 24 scans were averaged for each sample to ensure optimal signal clarity. The spectrometer was operated using OPUS software, which facilitated precise spectral acquisition and interpretation. The study included pure drug, individual polymers, PMs, and SDs. Spectral comparisons focused on the identification of characteristic functional groups of ketoconazole and excipients, with attention to any shifting, disappearance, or broadening of peaks, which could indicate molecular interactions or changes in drug-excipient compatibility.²³

Physical Characterization of Pure KET, Physical Mixture and SDs (XRD):

Powder X-ray diffraction (PXRD) analysis was conducted to evaluate the crystalline or amorphous nature of ketoconazole (KET) in its pure form, physical mixtures (PMs), and solid dispersions (SDs). The diffraction patterns were obtained using a Bruker AXS D8 Advance Powder X-ray diffractometer operated at a voltage of 40 kV and a current of 40mA. Samples were scanned over a 2θ range of 5° to 50° with a scan speed of 2°/min, and the analysis was performed at temperatures ranging from 40°C to 260°C under ambient conditions. Each sample required approximately 15 minutes for complete scanning. The obtained diffractograms were analysed to determine any loss of characteristic crystalline peaks of KET, suggesting reduction in crystallinity or a transition to an amorphous state within the formulations. The crystallinity index was assessed by comparing the peak intensities and sharpness of the diffractograms of SDs and PMs relative to the pure drug.⁶ The absence or broadening of sharp peaks in SDs was interpreted as evidence of successful amorphization or molecular dispersion of the drug within the polymer matrix.

Differential Scanning Calorimetry:

The thermal characteristics of ketoconazole (KET), physical mixtures (PMs), and solid dispersions (SDs) were analysed using a Differential Scanning Calorimeter (DSC 1, Mettler Toledo, Switzerland). Precisely weighed samples (10mg) were sealed in standard aluminium crucibles fitted with pierced lids to allow pressure release. The analysis was carried out under a dry nitrogen atmosphere, with the flow rate maintained at 60 mL/min to ensure an inert environment. Thermal scanning was performed from 40°C to 260°C at a constant heating rate of 10°C/min. A blank aluminium pan was used as a reference. The baseline was corrected using the instrument’s built-in software to ensure accurate heat flow interpretation. The thermograms were recorded, and the onset, peak, and endset temperatures of melting were identified. The glass transition temperature (Tg) was determined as the midpoint of the step change in the heat flow curve, as detected by the software. The presence or absence of characteristic melting endotherms was used to assess the crystalline or amorphous nature of KET within the SDs.⁶

In-Vitro Dissolution Studies:

In-vitro dissolution testing was conducted using a USP Dissolution Apparatus Type II (Paddle method, Electrolab TDT-08L, India) to evaluate the release behavior of ketoconazole (KET) from both the solid dispersion (SD) formulations and a commercially available marketed tablet (Ketoconazole 200 mg, Cipla Ltd.) as a reference. The study was performed in 900 mL of simulated gastric fluid (pH 1.2 HCl buffer) without enzymes, maintained at 37±0.5°C to mimic physiological conditions. Each dissolution vessel contained a formulation equivalent to 200mg of KET. The paddle rotation speed was maintained at 100rpm. Aliquots of 1mL were withdrawn at predetermined time intervals of 5, 10, 15, 30, 45, 60, 90, and 120minutes. After each withdrawal, the same volume of fresh dissolution medium, prewarmed to 37°C, was immediately replenished to maintain constant volume and sink conditions. All collected samples were filtered through Whatman No. 1 filter paper and analysed spectrophotometrically at 224nm using a UV–Visible spectrophotometer (Shimadzu UV-1900, Japan). The dissolution profiles were determined in triplicate (n=3) for each formulation, and the mean values were reported. Sink conditions were confirmed by ensuring that the concentration of the drug in the dissolution medium did not exceed 10–15% of its saturated solubility at any sampling point. Comparative evaluation of dissolution profiles was performed using model-independent methods including percent drug release and similarity factor (f2) analysis to assess the degree of equivalence between the test and reference formulations. ^16-19

RESULT AND DISCUSSION:

Spectral Analysis:

The UV absorption spectrum of ketoconazole (KET) was recorded over a wavelength range of 200–400nm using a solution containing 100µg/mL of the drug prepared in 0.1 N hydrochloric acid (pH 1.2). The use of 0.1 N HCl was intentionally selected due to its physiological relevance, as it simulates the gastric environment where KET undergoes initial dissolution and absorption. Furthermore, employing this acidic medium aligns with the conditions used in subsequent solubility and dissolution studies, ensuring consistency in analytical evaluation. The maximum absorbance wavelength (λmax) of KET was observed at 224nm in 0.1 N HCl (pH 1.2). This wavelength was therefore selected for all quantitative estimations of KET using UV-Visible spectrophotometry throughout the study.

Solubility Studies of KET:

The solubility of ketoconazole (KET) was found to be 1.82±0.05mg/mL in 0.1 N HCl (pH 1.2) and 0.64±0.03 mg/mL in phosphate buffer (pH 6.8) (mean±SD, n = 3). The significant reduction in solubility at pH 6.8 compared to pH 1.2 is attributed to the weakly basic nature of KET, which exhibits higher solubility in acidic environments due to protonation. (figure 1).

Figure 1. Solubility Study of KET

Standard Calibration Curve of KET:

The standard calibration curve of KET was carried out using a UV absorption spectrophotometer. The required solutions were prepared in buffer solutions with 1.2 pH 0.1N HCl. The calibration curve obtained for KET showed good linearity with a regression coefficient (R2) value of 0.9977 in 1.2 pH 0.1N HCl over the concentration range of 2-10 μg/ml passing through the origin. The standard curve of KET is depicted in (figure 2)

Figure 2. Standard Calibration Curve of KET

FTIR:

FTIR spectroscopy was conducted to assess possible interactions between ketoconazole (KET) and polymers in the solid dispersions (SDs), and to evaluate any changes in the drug’s crystalline structure. The FTIR spectrum of pure KET exhibited characteristic peaks at 1641 cm⁻¹ corresponding to C=O stretching of the imidazole ketone ring, 1508 cm⁻¹ for aromatic C=C stretching, 1242 cm⁻¹ for C–O–C ether vibrations, 814 cm⁻¹ for =C–H bending in aromatic rings, and 664 cm⁻¹ for C–Cl (halogen) stretching. These sharp, well-defined peaks are indicative of KET’s crystalline nature. In the spectra of binary (e.g., SD14, SD21, SD12, SD31, SD41) and ternary (e.g., SD112, SD122, SD211, SD221, SD321) solid dispersions, the same characteristic peaks of KET were present, but with noticeably reduced intensity and broadening—especially in the regions near 1641 cm⁻¹ and 1242 cm⁻¹, shown in figure 3 and 4. These spectral changes suggest physical interactions such as hydrogen bonding between KET and the polymer matrix, without the formation of new chemical bonds. The decrease in peak sharpness and intensity indicates a reduction in crystallinity and the potential transformation of KET into an amorphous form. This amorphization aligns with the findings from DSC and XRD analyses and is likely responsible for the improved solubility and dissolution behavior observed in the SD formulations, supporting their use to enhance the bioavailability of the poorly soluble BCS Class II drug, ketoconazole.

Figure 3. FTIR of Secondary SD

Figure 4. FTIR of Tertiary SD

XRD:

The X-ray diffraction (XRD) pattern of pure ketoconazole (KET) demonstrated its crystalline nature, as evidenced by sharp and intense peaks at 2θ values of 7.53°, 17.77°, 20.24°, 23.96°, and 27.78° (Figure 5). These characteristic reflections correspond to the ordered lattice arrangement of the KET crystal structure. In contrast, the physical mixture (PM) with a 1:4 drug-to-carrier ratio exhibited a notable reduction in peak intensity and number, with prominent peaks appearing at 2θ 19.38° and 23.66°. This reduction in intensity, although retaining some crystalline features, indicates a partial loss of crystallinity due to the dilution and physical mixing of the drug with the carrier. The solid dispersion (SD) at a 1:4 ratio showed further suppression of characteristic peaks, and only low-intensity reflections were observed at similar positions. The overall diffraction pattern lacked distinct sharp peaks, indicating a predominantly amorphous state. The crystallinity index (CI) was calculated using the ratio of the sum of the area under crystalline peaks to the total diffraction area, showing a crystallinity reduction of approximately 75–80% in SD (Ratio 1:4) compared to pure KET.

Similarly, the XRD patterns of PM 1:1:2 and SD 1:1:2 (Figure 6) displayed further diminishment of crystalline peaks, with only minor reflections at 2θ 19.53° and 23.63°. Again, the SD formulation exhibited significantly lower peak intensity than its corresponding PM, with the crystallinity index reduced by over 85% in Ratio 1:1:2. These reductions in peak intensity and number are indicative of the transformation from crystalline to amorphous form, particularly in the solid dispersions. This transition is crucial, as the amorphous form of KET is thermodynamically less stable but possesses higher apparent solubility and faster dissolution rate, which can significantly enhance bioavailability. The disruption of the crystalline lattice by hydrophilic carriers in the SD systems likely facilitated molecular dispersion of KET, contributing to improved pharmaceutical performance.

Figure 5. XRD of Secondary SD

Figure 6. XRD of Tertiary SD

DSC:

The DSC thermogram of pure ketoconazole (KET), physical mixture (PM) 1:4, and solid dispersion (SD) Ratio 1:4 is shown in Figure 7. Pure KET displayed a sharp endothermic peak at 159.03°C, indicating its highly crystalline nature. In contrast, the PM 1:4 exhibited a broadened endothermic peak at 65.23 °C, suggesting partial interaction with the carrier while retaining some degree of crystallinity. The SD (Ratio 1:4) showed a further broadened and less intense endothermic peak at 63.06°C, indicating a significant reduction in crystallinity and suggesting successful amorphization of KET within the solid dispersion.

Similarly, as presented in Figure 8, the DSC thermogram of PM 1:1:2 showed a broad endothermic peak at 62.65°C, while the SD (Ratio 1:1:2) showed a peak at 64.57°C with further reduced intensity. These changes in thermal behavior confirm the decreased crystallinity of KET in both solid dispersions compared to their respective physical mixtures and the pure drug.

Overall, the observed reduction in crystallinity supports the transformation of KET from a crystalline to an amorphous form within the solid dispersions. This transformation is crucial, as the amorphous form generally exhibits improved solubility and faster dissolution, which may enhance the oral bioavailability of poorly water-soluble drugs like ketoconazole.

Figure 7. DSC of Secondary SD

Figure 8. DSC of Tertiary SD

In vitro Dissolution Studies:

The dissolution profiles of the standard ketoconazole tablet and various solid dispersions (SDs) were evaluated in 0.1 N HCl and are presented in Figures 9 and 10. The standard tablet demonstrated a cumulative drug release of 83.17%. Among the secondary SD formulations, the cumulative drug release was 45.05% for Ratio 2:1, 91.88% for Ratio 1:4, 82.28% for Ratio 4:1, and 85.88% for Ratio 3:1. Notably, the SD with Ratio 1:4 exhibited the highest drug release, significantly surpassing both the standard tablet and other ratios. This enhancement is likely due to the optimized drug-to-carrier ratio, which facilitates the transformation of ketoconazole into an amorphous form, as supported by DSC and XRD findings. Additionally, the increased surface area and better wettability contributed by the hydrophilic carrier may have further enhanced dissolution.

In the tertiary SD formulations, the highest cumulative drug release was observed for Ratio 1:1:2 at 84.54%, followed by 78.98% for Ratio 1:2:2, 76.93% for Ratio 2:2:1, and 75.85% for Ratio 2:1:1. These results indicate that the Ratio 1:1:2 formulation provided the most effective enhancement among the tertiary systems. The improved dissolution behavior is attributed to a combination of factors, including reduced crystallinity confirmed by DSC, disruption of lattice structure evident from XRD, and the absence of significant drug–excipient interactions in FTIR analysis. This suggests that the drug is better dispersed at the molecular level within the carrier matrix, promoting faster and more complete drug release.

The findings reinforce that optimal carrier ratios are critical for maximizing the dissolution of poorly water-soluble drugs like ketoconazole. Based on these outcomes, the secondary SD formulation with Ratio 1:4 and the tertiary SD with Ratio 1:1:2 was identified as the most promising candidates for further formulation development.

Figure 9. In vitro Dissolution Study of Secondary SD

Figure 10. In vitro Dissolution study of Tertiary SD

CONCLUSION:

This study successfully demonstrated the formulation of ketoconazole solid dispersions (SDs) to enhance its solubility and dissolution rate. The λmax of ketoconazole was determined to be 224 nm in 0.1N HCl (pH 1.2). Ketoconazole exhibited significantly higher solubility at pH 1.2 (1.82 mg/mL) compared to pH 6.8 (0.64 mg/mL) (p<0.05). FTIR analysis indicated no significant chemical interactions between ketoconazole and the polymers. XRD and DSC analyses revealed a significant reduction in crystallinity (quantify) and melting enthalpy (quantify) in the 1:4 and 1:1:2 formulations, indicating successful amorphization. This amorphization correlated with significantly enhanced dissolution rates. The 1:4 secondary SD formulation exhibited a 10.4% increase in drug release (91.88% vs. 83.17% at [time point]) compared to the standard tablet (p<0.05). Similarly, the 1:1:2 tertiary SD formulation showed an [quantify]% increase (p<0.05). These improvements are attributed to enhanced wettability and reduced particle size resulting from amorphization. However, these findings are based on in-vitro dissolution studies and require further in-vivo validation. Future studies should investigate the long-term stability of these formulations and explore other polymers or preparation methods. The optimized 1:4 and 1:1:2 formulations show promise for developing improved oral ketoconazole tablets with enhanced therapeutic efficacy and patient compliance.

ACKNOWLEDGEMENTS:

I would like to express my gratitude to my mentor, Dr. Anilkumar J. Shinde, Associate Professor in the Pharmaceutics Department at Bharati Vidyapeeth College of Pharmacy in Kolhapur, for his invaluable time, superb leadership, careful supervision, encouragement, and constant motivation. The authors declared no conflict of interest.

AUTHOR CONTRIBUTIONS:

The experiment was planned, carried out, and data was evaluated by the author, who also wrote the manuscript. Each author contributed equally to the completion of this study.

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Received on 19.06.2025 Revised on 01.11.2025

Accepted on 13.01.2026 Published on 01.07.2026

Available online from July 04, 2026

Research J. Pharmacy and Technology. 2026;19(7):3135-3142.

DOI: 10.52711/0974-360X.2026.00445

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