A system for producing buccal stripes from cineole

Abstract

A system (100) for producing buccal cineole strips, comprising: a) a solution preparation unit (102) for preparing a polymer solution containing water, cineole drug, plasticizer and glycerin; b) a homogenization unit (104) connected to the solution preparation unit (102) to produce a homogeneous solution of the polymer solution; c) a casting arrangement (106) configured to pour a prepared homogeneous polymer solution onto a mold for the production of buccal strips; d) a drying unit (108) connected to the casting device (106) and comprising an air drying chamber (108a) for air drying the cast uniform polymer solution; and e) a storage unit (110) comprising a desiccator (110a) enabling the storage of the prepared buccal strips of cineole.

Description

AREA OF INVENTION

[0001] The present disclosure relates to a system for the production of buccal cineole strips. More precisely, the present invention relates to the production of buccal cineole strips and the evaluation of their effective release through the oral cavity using a natural bioadhesive polymer. BACKGROUND OF THE INVENTION

[0002] There is a significant association between cardiovascular disease and periodontitis. The link between these conditions lies in the inflammatory nature of gum disease, which releases pro-inflammatory chemicals into the bloodstream and may trigger systemic inflammatory responses that can impair cardiovascular health. Studies have found that individuals with gum disease have a 25% higher risk of heart disease than those with healthy gums.

[0003] Traditional treatment methods for periodontal disease often involve systemic medications or topical applications, which have limited efficacy due to short retention times and inconsistent drug delivery. Conventional oral medications can lead to reduced bioavailability due to first-pass metabolism, while topical applications are frequently washed away by saliva, resulting in inadequate therapeutic outcomes. Furthermore, existing treatment options often require multiple daily doses, leading to low patient compliance and inconsistent treatment results.

[0004] Cineole, a natural compound with proven therapeutic properties, has shown promise in the treatment of gingivitis. However, its effective delivery to the target site remains a challenge with conventional dosage forms. The oral cavity, due to its accessibility, rich blood supply, and ability to bypass first-pass metabolism, represents an ideal site for drug delivery. Therefore, there is a need for a treatment approach that addresses this drawback.

[0005] In light of the preceding discussion, the present invention provides a system for the production of buccal strips from cineole, wherein the produced buccal strips, manufactured using natural bioadhesive polymers, overcome the aforementioned limitations by offering a convenient, controlled-release treatment approach that can be easily applied and removed as needed. This approach not only ensures better patient compliance but also offers the potential for improved therapeutic outcomes through sustained drug delivery directly at the site of action. SUMMARY OF THE INVENTION

[0006] This disclosure relates to a system for the production of cineole-loaded buccal strips. Furthermore, the invention aims to evaluate the effective release of the produced strips through the oral cavity using a natural bioadhesive polymer. The cineole-loaded buccal strips are produced using pectin sodium alginate and gelatin as the polymer in three different ratios. The results of preformulation studies showed that, according to FTIR analyses, there is no conflict between the drug and the excipients. Based on folding strength and ideal tensile strength, P2 (pectin), S5 (sodium alginate), and G8 (gelatin) were selected from nine formulations. To produce flexible strips without significantly impairing their release properties, glycerin was used as a plasticizer.All batches were tested for percentage moisture absorption, percentage moisture content, percentage drug content, percentage elongation, percentage tensile strength, and percentage adhesive strength. No discernible change in drug content was observed between the strips of the nine formulations. Evaluation of the prepared strips showed that formulations P2, S5, and G8 exhibited in vitro release profiles of 98.41%, 78.36%, and 99.41%, respectively. Release kinetics confirmed that formulation S5 followed a non-Fickian zero-order diffusion model. Ex vivo experiments showed a drug release of 66.86% after 12 hours.Furthermore, the polymer exhibited sustained release properties, and according to stability analysis, no changes in the original condition of the prepared strips were observed over a period of three months at 40 °C ± 2 °C / 75 ± 5 % relative humidity.

[0007] The present disclosure is intended to provide a system for the production of buccal strips from cineole. The system comprises: a solution preparation unit for producing a polymer solution containing water, cineole drug, plasticizer, and glycerin; a homogenization unit connected to the solution preparation unit for producing a homogeneous solution of the polymer solution; a casting device configured to pour the produced homogeneous polymer solution onto a mold for the production of buccal strips; a drying unit connected to the casting device, comprising an air-drying chamber for air-drying the cast homogeneous polymer solution; and a storage unit comprising a desiccator for storing the produced buccal strips from cineole.

[0008] In one embodiment, the solution preparation unit comprises: a mixing vessel facilitating the preparation of a polymer solution, wherein the mixing vessel initially contains only water; an automatic drug delivery unit connected to the mixing vessel, enabling the addition of cineole to the water-filled mixing vessel; and a plasticizer delivery unit connected to the mixing vessel, enabling the addition of glycerin as a plasticizer to the mixing vessel.

[0009] In one embodiment, the homogenization unit comprises a stirring mechanism connected to the mixing vessel of the solution preparation unit and configured to mix the added components in the mixing vessel to obtain a homogeneous polymer solution of water, cineole drug, plasticizer and glycerin, wherein the stirring mechanism comprises a high-speed homogenizer with adjustable speed and temperature controls.

[0010] In one embodiment, the casting arrangement comprises a casting platform configured to hold a mold into which the prepared polymer solution is poured for casting by a solution dispensing and distribution mechanism to ensure a uniform distribution of the homogenized polymer solution.

[0011] In one embodiment, the drying unit also includes: a temperature and humidity control mechanism for regulating the parameters in the air drying chamber; and one or more air circulation fans integrated into the air drying chamber.

[0012] In one embodiment, the air drying chamber includes a racking system designed to accommodate multiple molds simultaneously.

[0013] In one embodiment, the desiccator of the storage unit includes a mechanism for temperature and humidity control and monitoring.

[0014] One objective of the present invention is to provide a system for the production of buccal cineole strips.

[0015] Another objective of the present invention is the production of cineole buccal strips using various polymers and the evaluation of their effective release through the oral cavity.

[0016] To provide oral strips that allow direct entry of the drug into the systemic circulation to achieve immediate relief from toothache and inflammation due to gingivitis.

[0017] To provide treatment for gingivitis by taking into account the problems associated with the effective delivery of the drug to the target site.

[0018] To further clarify the advantages and features of the present disclosure, a more detailed description of the invention is given with reference to specific embodiments thereof, which are illustrated in the accompanying drawing. It should be noted that this drawing only represents typical embodiments of the invention and is therefore not to be considered as limiting its scope. The invention is described and explained with additional details and information with reference to the accompanying drawing. BRIEF DESCRIPTION OF THE FIGURE

[0019] These and other features, aspects, and benefits of this disclosure will be better understood when the following detailed description is read with reference to the accompanying drawing, in which the same symbols consistently represent the same parts. The following applies: Fig.Figure 1 shows a block diagram of a system for the production of buccal cineole strips according to an embodiment of the present disclosure.

[0020] Furthermore, those skilled in the art will recognize that elements in the drawing are shown for the sake of simplicity and are not necessarily drawn to scale. For example, the flowcharts illustrate the method by outlining the main steps to enhance understanding of aspects of this disclosure. Additionally, with regard to the design of the device, one or more components of the device may be represented in the drawing by conventional symbols, and the drawing may show only the specific details relevant to understanding the embodiments of this disclosure, so as not to clutter the drawing with details that are readily apparent to those skilled in the art who benefit from the description herein. DETAILED DESCRIPTION:

[0021] To further the understanding of the principles of the invention, reference is now made to the embodiment shown in the drawing, which is described in specific language. However, it is clear that this is not intended to limit the scope of the invention, since such changes and further modifications of the illustrated system and such further applications of the principles of the invention as shown therein are considered as would normally occur to a person skilled in the art in the field to which the invention relates.

[0022] It is clear to the person skilled in the art that the preceding general description and the following detailed description are exemplary and explanatory of the invention and are not intended as a limitation of it.

[0023] References in this specification to “an aspect”, “another aspect”, or similar formulations mean that a particular feature, structure, or property described in connection with the embodiment is included in at least one embodiment of the present disclosure. Therefore, occurrences of the phrase “in one embodiment”, “in another embodiment”, and similar formulations in this specification may all refer to the same embodiment, but need not.

[0024] The terms "includes," "comprehensive," or other variations thereof are intended to cover non-exclusive inclusion, so that a process or method that includes a list of steps may include not only those steps but also other steps not expressly listed or inherent in such process or method. Likewise, one or more devices, subsystems, elements, structures, or components preceded by "includes...a" do not, without further limitations, exclude the existence of other devices, subsystems, elements, structures, components, or additional devices, subsystems, elements, structures, or components.

[0025] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as they are generally understood by a person skilled in the art in the field to which this invention belongs. The system, methods, and examples provided herein are for illustrative purposes only and are not to be understood as limiting.

[0026] Embodiments of the present disclosure are described in detail below with reference to the attached drawing.

[0027] Fig. Figure 1 shows a block diagram of a system (100) for the production of buccal cineole strips according to an embodiment of the present disclosure.

[0028] With reference to Fig.1 The system (100) comprises a solution preparation unit (102) for preparing a polymer solution containing water, cineole drug, plasticizer, and glycerin; a homogenization unit (104) connected to the solution preparation unit (102) to produce a homogeneous solution of the polymer solution; a casting arrangement (106) configured for casting the prepared homogeneous polymer solution onto a mold for producing buccal strips; a drying unit (108) connected to the casting arrangement (106) and comprising an air drying chamber (108a) for air drying the cast homogeneous polymer solution; and a storage unit (110) comprising a desiccator (110a) that enables the storage of the prepared cineole buccal strips.

[0029] In one embodiment, the solution preparation unit (102) comprises: a mixing vessel (102a) that facilitates the preparation of the polymer solution, wherein the mixing vessel initially contains only water; an automated drug delivery unit (102b) that is connected to the mixing vessel (102a) and enables the addition of cineole to the water-containing mixing vessel (102a); and a plasticizer delivery unit (102c) that is connected to the mixing vessel (102a) and enables the addition of glycerin as a plasticizer to the mixing vessel (102a).

[0030] In one embodiment, the homogenization unit (104) comprises a stirring mechanism (104a) connected to the mixing vessel (102a) of the solution preparation unit and configured to mix the added components in the mixing vessel (102a) to obtain a homogeneous polymer solution of water, cineole drug, plasticizer and glycerin, wherein the stirring mechanism (104a) comprises a high-speed homogenizer with adjustable speed and temperature control.

[0031] In one embodiment, the casting arrangement (106) comprises a casting platform (106a) configured to hold a mold into which the prepared polymer solution is poured for casting by a solution dispensing and distribution mechanism (106b) to ensure a uniform distribution of the homogenized polymer solution.

[0032] In one embodiment, the drying unit (108) also comprises: a temperature and humidity control mechanism (108b) for controlling the parameters in the air drying chamber (108a); and one or more air circulation fans (108c) integrated into the air drying chamber (108a).

[0033] In one embodiment, the air drying chamber (108a) comprises a racking system designed to accommodate multiple molds simultaneously.

[0034] In one embodiment, the desiccator (110a) of the storage unit (110) includes a mechanism for temperature and humidity control and monitoring.

[0035] The present invention relates to a system for producing buccal strips from cineole, wherein the production of cineole-loaded buccal strips is carried out using pectin, sodium alginate, and gelatin as polymers in three different ratios, and wherein a total of nine formulations of P2 (pectin), S5 (sodium alginate), and G8 (gelatin) are produced. Gelatin is used as a plasticizer for the production of flexible strips without significantly impairing their release properties.

[0036] In one embodiment, preformulation studies are conducted prior to the manufacture of the strips. The aim of these studies is to generate useful information, and they investigate the physical and chemical properties of the drug product alone and in combination with excipients. The preformulation studies include: determining absorption maxima, evaluating the physical appearance, determining solubility, determining the melting point, determining the standard curve, and conducting infrared spectroscopy studies for compatibility purposes.

[0037] A detailed approach to conducting preformulation studies is described. The preformulation study is specifically designed to investigate drug properties and compatibility with bioadhesive polymers to ensure optimal formulation and release efficiency. Determination of the absorption maxima:

[0038] To identify the drug, the absorption maxima (λ max) of cineole were determined using UV-Vis spectrophotometry (UV-Vis). This technique provides important insights into the chromophoric regions of the cineole molecular structure. Organic molecules in solution absorb light at specific wavelengths within the UV-Vis spectrum, influenced by the electronic transitions associated with absorption. Cineole was prepared in a range of concentrations (5, 10, 15, 20, and 25 µg / ml) in distilled water and placed in a standard cuvette. The solution was scanned with a UV spectrophotometer between 200 and 400 nm, revealing a peak absorption at 240 nm. Consequently, all subsequent measurements were performed at this wavelength to ensure consistency and accuracy. Physical properties:

[0039] The physical appearance of cineole, including color, taste, and odor, was assessed to determine basic properties. To evaluate color, a small amount of cineole was placed in a test tube under well-lit conditions, allowing for a clear visual assessment. Taste and odor were tested by using a minimal amount of cineole, which was carefully tasted and smelled to evaluate its sensory properties. Solubility test:

[0040] The solubility of cineole, a crucial factor in its formulation, was investigated in various solvents to determine the optimal conditions for homogeneous dispersion. A 10 mg sample of cineole was suspended at room temperature in 10 mL of different solvents in tightly sealed test tubes and shaken by hand. The observed solubility profiles were compared to standard solubility classifications ranging from "very soluble" to "practically insoluble." These classifications are defined by the amount of solvent required to dissolve one part of cineole. For example, substances classified as "very soluble" require less than one part solvent, while substances classified as "insoluble" require 10,000 parts or more. Preparation of the standard curve:

[0041] To enable precise dosage formulation and release profiling, a standard cineole curve was generated. A precisely weighed amount of cineole (100 mg) was dissolved in ethanol and diluted to a final volume of 100 ml, resulting in a concentration of 1000 µg / ml in a phosphate buffer solution at pH 7.4. A 10 ml aliquot of this stock solution was further diluted to 100 ml, yielding a working concentration of 100 µg / ml. Using a UV spectrophotometer, the absorbance was measured at the defined absorbance maximum of 240 nm with phosphate buffer as the blank. Compatibility studies (FTIR):

[0042] The compatibility between cineole and the bioadhesive polymer was investigated using Fourier-transform infrared spectroscopy (FTIR). Samples of cineole and the polymer were analyzed by dispersing the materials in dry potassium bromide. Under identical conditions, spectra in the range of 2000 cm⁻¹ were obtained. -1 up to 500 cm -1 FTIR spectra enabled the identification of any shifts or interactions between cineole and the polymer, visible through specific absorption peaks, providing important information on molecular compatibility that is essential for the stability and efficacy of the mouth strip formulation.

[0043] The cineole buccal strip was produced using the proposed system based on solvent casting. The film was prepared in a Petri dish with a diameter of 7.6 cm and a capacity of 6 ml. The polymer composition contains a total of 400 mg in the buccal strip. The polymer solutions were prepared with water. The polymer solution was added to the cineole drug. Then, plasticizer and glycerin were mixed and thoroughly stirred to obtain a homogeneous solution. The resulting homogeneous solution was poured onto the mold and air-dried for 24 hours. After 24 hours, the dried films were removed and stored in desiccators for further investigation.

[0044] In one embodiment, the preparation of the formulation for the strips is optimized by conducting various trials regarding the concentration of solvent, plasticizer and polymer in order to obtain a buccal strip with good film properties such as uniform thickness, uniform weight, homogeneous drug dispersion and optimal tensile strength by adding glycerin as a plasticizer and to produce flexible strips without significantly impairing their release properties.

[0045] 1: The ingredients and their quantities for making buccal strips S. No INGREDIENTS 2nd place (pectin) Season 5 (Sodium alginate) G8 (gelatin) 1 Cineole (mg) 100 100 100 100 100 100 100 100 100 2 Polymer (mg) 300 400 500 400 300 200 400 300 500 3 Water (ml) 5 5 5 5 5 5 5 5 5 4 Glycerin (ml) 0.15 0.15 0.15 0.15 0.15 0.15 0.15 0.15 0.15

[0046] The prepared cineole buccal strips are subjected to physicochemical investigations in which the uniformity of weight, the thickness of the strip, the drug content, the folding strength, the percentage moisture absorption, the percentage moisture content, the pH value of the surface, the percentage elongation and the tensile strength are determined.

[0047] The formulated cineole buccal strips underwent preliminary evaluation tests. Strips with defects, such as trapped air, uneven thickness, weight, or inconsistent content, were excluded from further studies. Uniformity of weight:

[0048] To assess weight uniformity, five strips were randomly selected from each batch and weighed. After drying at 60 °C for four hours, the average weight of three strips was calculated to determine uniformity across the entire batch. Thickness measurement:

[0049] The strip thickness was measured at various points using a digital caliper, with three strips selected from each formulation to ensure uniformity. The average thickness values ​​were recorded. Determination of the drug content

[0050] The active ingredient content was analyzed by immersing the strips in 100 ml of phosphate-buffered saline solution (pH 7.4) and stirring with a magnetic bead for five hours. The solution was then filtered and the active ingredient concentration was determined spectrophotometrically at 240 nm. Foldable endurance

[0051] Folding resistance was assessed by repeatedly folding a strip at the same point until it broke. The total number of folds was recorded. This test provided a measure of flexibility and strength. Percentage moisture absorption and moisture content

[0052] To determine moisture absorption, the strips were weighed and placed in desiccators containing aluminum chloride for 24 hours. They were then weighed again to calculate the percentage increase in moisture relative to the initial weight. Similarly, the percentage moisture content was determined by storing the strips in desiccators containing calcium chloride, weighing them again after 24 hours, and calculating the difference. Determination of the pH value of the surface:

[0053] To determine the pH value of the surface, the strips were soaked for two hours at room temperature in contact with 1 ml of distilled water. A pH electrode was then placed on the strip surface to record the pH value after equilibration. Percentage elongation and tensile strength

[0054] The percentage elongation was determined by measuring the increase in strip length under applied tension, indicating flexibility and plasticity. The tensile strength, the maximum stress applied before the strip breaks, was calculated by dividing the applied load at break by the strip's cross-sectional area. In vitro determination of buccoadhesive strength:

[0055] The ex vivo buccoadhesive strength of the cineole buccal strip was determined using a modified balance method with fresh goat buccal mucosa from a local slaughterhouse. The mucosal membrane was separated by removing the underlying fat and loose tissue and then washed with distilled water. The prepared mucosa was cut into pieces, rinsed with phosphate buffer (pH 7.4), and tied to a glass vial, which was then placed in a glass beaker filled with phosphate buffer (pH 7.4) at 37 ± 1 °C. The buccal strip was glued to the underside of a wooden block and weighted with a 5-gram weight for initial contact. After three minutes, weights were incrementally added to the balance until the strip detached from the mucosal membrane. The buccoadhesive strength was determined by subtracting 5 grams from the total weight required to detach the strip. Treatment with cellophane membranes:

[0056] The cellophane membrane used in the drug permeation study underwent a series of preparatory treatments. First, it was boiled in distilled water for one hour, washed three times with fresh distilled water, and soaked in ethanol for 24 hours. It was then rinsed and treated with 0.3% sodium sulfite at 60°C for two minutes, followed by immersion in 0.2% sulfuric acid. Finally, the membrane was treated with boron buffer (pH 9) and stored in this solution until used for permeation studies. Studies on drug permeation:

[0057] The in vitro release rate of cineole from the oral saliva strip was evaluated over a 12-hour period using an open-end diffusion tube and phosphate buffer (pH 7.4) as the diffusion medium. A cellophane membrane was attached to one end of the tube and immersed in a receptor compartment containing 400 ml of phosphate buffer (pH 7.4), which was continuously stirred at a moderate speed and maintained at 37 ± 2 °C. Samples were taken at regular intervals, and the removed volume was replaced with fresh diffusion medium. The samples were analyzed using a UV spectrophotometer set to 240 nm.

[0058] The tests mentioned above enable a comprehensive evaluation of the buccal strips and ensure their consistency, durability, and suitability for drug delivery. This structured evaluation provided detailed data on both the buccoadhesive strength and the drug release profile of the cineole buccal strip. Ex vivo study on buccal permeation for the S4 formulation:

[0059] The ex vivo oral permeation study was performed using goat oral mucosa to evaluate the release of cineole from the oral strip formulation (S4) through the oral cavity. The receptor compartment was set up in a 500 ml beaker containing 400 ml of phosphate buffer (pH 7.4), which was maintained at 37 ± 0.5 °C and continuously stirred at 900 rpm to simulate physiological conditions. The cineole buccal strip was placed on the goat's oral mucosa and attached to an open glass cylinder, which was then immersed in freshly prepared phosphate buffer on a magnetic stirrer. At regular intervals of 0, 5, 10, 15, 30, 45, 60, 120, 180, 240, 300, 360, 420, 480, 540, 600, 660, and 720 minutes, 5 ml samples were taken from the receptor medium. After each withdrawal, an equal volume of fresh buffer was added to maintain constant volume and concentration.The samples were analyzed spectrophotometrically at 240 nm using phosphate buffer as a blank sample. Release kinetics and mechanism analysis:

[0060] The release kinetics of cineole from the oral strip were analyzed by fitting in vitro release data to several kinetic models: zeroth-order, first-order, Higuchi, Hixson-Crowell, and Korsmeyer-Peppas equations. The zeroth-order model (Q = kot) represents a concentration-independent release and produces a linear graph of cumulative drug release versus time. The first-order model {ln (100 - Q) = ln Q - k1t} describes the concentration-dependent release, with a linear graph of the logarithmic percentage of remaining drug versus time. The Higuchi model (Q = kt^1 / 2) investigates release based on diffusion mechanisms, in which the initially dissolved drug diffuses out of the polymer matrix.

[0061] Additionally, the release mechanism was assessed by applying the initial 60% drug release to the Korsmeyer-Peppas equation (Q = k). p The release exponent (n) was adjusted, where the release exponent characterizes the release mechanism. In matrix diffusion-controlled systems, the release rate depends primarily on the dissolution rate at the interface between the bath solution and the solid drug. In hydrophilic matrices, water penetrates the polymer and forms a gel layer that controls drug release through a combination of diffusion and erosion. The Hopfenberg model, described by the equation [1 - Mt / M]1 / 3 = 1 - kt, was used to determine whether the release is erosion-driven, using a plot of [1 - Mt / M] 1 / 3 which would result in a linear relationship against time for erodible matrix systems. Accelerated stability tests:

[0062] Stability tests determine the duration for which a drug retains its properties from the time of manufacture. In this study, the drug is subjected to high stress (such as elevated temperature and humidity) to accelerate degradation. This helps to identify potential instability problems within a shorter timeframe. Stability tests are crucial for determining a drug's shelf life and ensuring that patients receive a consistent dose throughout its storage period. Ideally, data should be collected from at least three primary batches produced at pilot scale, which ensures reliability and consistency across larger production volumes.

[0063] The absorption maxima (λ max) of cineole showed a peak at 240 nm. The standard curve showed the results presented in Table 2 below, demonstrating that the standard curve has a good regression coefficient of r = 0.9976 and exhibits linearity. Table 2: Standard curve of cineole S. No Drug concentration (µg / ml) Absorption at 240 nm 1 0 0 2 10 0.0568 3 20 0.1074 4 30 0.1531 5 40 0.2094 6 50 0.2646 7 60 0.2916

[0064] Nine batches of cineole-loaded buccal strips were successfully formulated using the proposed system based on a solvent casting technique. The production of cineole-loaded buccal strips involves optimizing various formulation parameters, including the drug-polymer ratio and excipients, to obtain a strip that is thin, transparent, smooth, stable, and highly permeable. Natural bioadhesive polymers were used to maintain the integrity and adhesion of the strip. FTIR analysis of the drug, excipients, and formulations confirmed the absence of any additional peaks or peak broadening, indicating compatibility between the drug and excipients.

[0065] Through optimization, the three best formulations—pectin (P2), sodium alginate (S4), and gelatin (G7)—were selected based on their folding strength and optimal tensile strength. Adjustments to the polymer content showed that a polymer amount below 0.4 g made handling difficult, while amounts above 0.4 g caused the strips to become thick or break easily, resulting in low tensile strength. Glycerin was added as a plasticizer (0.05 ml per strip) to improve flexibility without significantly affecting drug release properties. Too much glycerin led to stiffness, so its amount was carefully controlled. As a plasticizer, glycerin is added to the strips, which softens the polymer particles, promotes latex coalescence, and facilitates strip formation.

[0066] All batches underwent thorough testing for moisture absorption (%), moisture content (%), thickness, crease strength, active ingredient content (%), elongation (%), tensile strength, and tack. Among the formulations, S4 exhibited the highest values ​​in various parameters, including moisture absorption (%) (3.57%), moisture content (%) (3.27%), thickness (0.35 mm), crease strength (%) (265%), active ingredient content (%) (96.24%), elongation (%) (%), and tensile strength (%) (7.66 kg / mm²). 2 ) and adhesive strength (21.66). In a visual comparison with a commercially available buccal strip (Listerine Pocket Packs), the selected formulation showed no significant difference in active ingredient content between the nine formulations, confirming a consistent and homogeneous distribution of the active ingredient in the strips.

[0067] The in vitro release profile of the cineole-loaded buccal strip formulations showed a release of P2 at 98.41%, S4 at 78.36%, and G7 at 99.41% over a 12-hour period. Drug release exhibited a biphasic pattern, with an initial rapid release followed by a sustained release phase. Kinetic modeling of the 12-hour in vitro release data showed a high correlation coefficient (r). 2 ), which suggests that drug release followed zero-order kinetics and was controlled by a non-Fickian diffusion mechanism.

[0068] Further analysis of the S4 formulation was performed using the Korsmeyer-Peppas equation to determine the release exponent (n) and thus elucidate the drug diffusion mechanism. With a high correlation coefficient (r = 0.984) and an n value of 0.936, the release mechanism was identified as non-Fickian, namely Super Case II transport. Based on in vitro release and physicochemical evaluation, S4 (sodium alginate) proved to be the best formulation. This formulation was then subjected to additional ex vivo and stability studies.

[0069] Ex vivo studies have shown that the S4 formulation maintains a drug release of 66.86% over 12 hours, confirming the polymer's delayed-release capability. Stability studies conducted over three months under controlled conditions (40°C ± 2°C and 75 ± 5% relative humidity) showed no significant changes in appearance, color, texture, drug content, or drug release properties, confirming the formulation's stability.

[0070] This invention comprises cineole buccal strips manufactured using natural bioadhesive polymers such as pectin, sodium alginate, and gelatin. The strips demonstrated significant penetration of the oral cavity (ex vivo) and sustained drug release over 12 hours. Release kinetics showed that the strip formulation followed a non-Fickian zero-order diffusion model, fulfilling the project objectives and proving the efficacy of the cineole-loaded buccal strips.

[0071] The drawing and the preceding description provide examples of embodiments. Those skilled in the art will recognize that one or more of the described elements can be combined to form a single functional element. Alternatively, certain elements can be divided into several functional elements. Elements from one embodiment can be added to another embodiment. For example, the sequences of the processes described herein can be changed and are not limited to the manner described herein. Furthermore, the actions of any flowchart need not be implemented in the order shown; nor do all actions necessarily need to be performed. Actions that are not dependent on other actions can also be performed in parallel with the other actions. The scope of embodiments is in no way limited by these specific examples.Numerous variations are possible, whether explicitly stated in the specification or not, such as differences in structure, dimensions, and material use. The range of embodiments is at least as broad as specified in the following claims.

[0072] Advantages, other merits, and problem solutions have been described above in relation to specific embodiments. However, the advantages, merits, problem solutions, and all components that may lead to an advantage or solution occurring or becoming more apparent are not to be construed as a critical, necessary, or essential feature or component of any or all claims. REFERENCES 100 A System for the Production of Buccal Cineole Strips. 102 A solution preparation unit 102a Mixing container 102b Automated Drug Delivery Unit 102c Plasticizer dosing unit 104 homogenization unit 104a Stirrer 106 Casting assembly 106a Casting Stage 106b Mechanism for Dispensing and Distributing the Solution 108 drying units 108a Air drying chamber 108b Mechanism for temperature and humidity control 108c One or more air circulation fans 110 storage units 110a Desiccator

Claims

[1] A system (100) for producing buccal cineole strips, comprising: a) a solution preparation unit (102) for preparing a polymer solution containing water, cineole drug, plasticizer and glycerin; b) a homogenization unit (104) connected to the solution preparation unit (102) for preparing a homogeneous solution of the polymer solution; c) a casting assembly (106) configured to pour a prepared homogeneous polymer solution onto a mold for producing buccal strips; d) a drying unit (108) connected to the casting device (106) and comprising an air drying chamber (108a) for air drying the cast uniform polymer solution; and e) a storage unit (110) comprising a desiccator (110a) enabling storage of the prepared buccal strips of cineole. [2] The system (100) of claim 1, wherein the solution preparation unit (102) comprises: a mixing vessel (102a) which facilitates the preparation of the polymer solution, the mixing vessel initially containing only water; an automated drug delivery unit (102b) connected to the mixing container (102a) and enabling the addition of cineole into the water-filled mixing container (102a); a plasticizer dispensing unit (102c) connected to the mixing container (102a) and enabling the addition of glycerin as a plasticizer to the mixing container (102a). [3] The system (100) according to claim 1, wherein the homogenization unit (104) comprises a stirring mechanism (104a) connected to the mixing tank (102a) of the solution preparation unit and configured to mix the added components in the mixing tank (102a) to obtain a homogeneous polymer solution of water, cineole drug, plasticizer, and glycerin, wherein the stirring mechanism (104a) comprises a high-speed homogenizer with adjustable speed and temperature controllers. [4] The system (100) of claim 1, wherein the casting assembly (106) comprises a casting platform (106a) configured to hold a mold into which the prepared polymer solution is poured for casting by a solution dispensing and distribution mechanism (106b) to achieve uniform distribution of the homogenized polymer solution. [5] System (100) according to claim 1, wherein the drying unit (108) further comprises: a temperature and humidity control mechanism (108b) for controlling the parameters in the air drying chamber (108a); and one or more air circulation fans (108c) integrated into the air drying chamber (108a). [6] System (100) according to claims 1 and 5, wherein the air drying chamber (108a) comprises a shelving system designed to hold a plurality of molds simultaneously. [7] The system (100) of claim 1, wherein the desiccator (110a) of the storage unit (110) includes a temperature and humidity control and monitoring mechanism.

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