Formulation and Evaluation of Mouth Dissolving Film of Ginseng

Rakshanda Dhuliya¹, Yogita Ale²*, Neha Kandpal³, Nidhi Nainwal¹, Vikash Jakhmola⁴

¹Bhagwant Global University (BGU), Kotdwar, Pauri Garhwal, Uttarakhand, India.

²Department of Pharmaceutics, Uttaranchal Institute of Pharmaceutical Sciences,

Uttaranchal University, Dehradun, 248007, Uttarakhand, India.

³College of Pharmacy, COER University, Roorkee, Haridwar, Uttarakhand, India.

⁴Department of Pharmaceutical Chemistry, Uttaranchal Institute of Pharmaceutical Sciences,

Uttaranchal University, Dehradun, 248007, India.

*Corresponding Author E-mail: yogitaale7@gmail.com

ABSTRACT:

BACKGROUND: Ginseng is one of the most significant medicinal plants that has been used for thousands of years. Ginsenosides are the major constituents of ginseng and possess low bioavailability below 5%. Hence it is necessary to enhance the bioavailability through various approaches. Ginseng's limited oral bioavailability can be overcome using fast mouth-dissolving film. AIM and OBJECTIVE: The research study aimed to formulate fast-mouth dissolving ginseng oral films and analyze the effect of various Hydroxypropyl methylcellulose (HPMC) E15, HMPC E5, and natural gums. METHOD: The solvent casting technique was employed to formulate the films. FTIR analysis was used to investigate the relationship between the polymer and Ginseng in the film formulation. The formulated films were evaluated for moisture content, surface pH, percentage drug content, thickness, disintegration time, folding endurance, and percentage elongation and in-vitro drug release. RESULT: The optimized formulation F3 showed the highest drug release of 90.89%. The formulation's drug content range was recorded between 86.23% to 94.52%. Korsmeyer-Peppas was the best-fit model from fast-dissolving film based on the in-vitro drug release kinetic model results. CONCLUSION: Ginseng mouth dissolving films may give fast action which increases the bioavailability. Mouth-dissolving film provides better patient compliance in terms of ease of administration and therapeutic effectiveness compared to commercial formulations such as instant release and orally disintegrating tablets.

KEYWORDS: Mouth dissolving film, Ginseng, Natural gums, Hydroxypropyl methylcellulose E15, Release kinetics.

INTRODUCTION:

One of the most popular methods for administering medication is oral since it is more practical, affordable, and easy to administer, which increases patient compliance¹. Recent advancements in formulation technology offer oral dose options for pediatric, geriatric, immobile, nauseated, or noncompliant patients.^2,3

Noval bioadhesive or mucoadhesive dosage forms, such as patches, adhesive tablets, gels, and, in recent years, polymeric films in oral cavity administration and mouth-dissolving film (MDFs), have been the focus of formulation studies recently^4,5.

MDFs, a revolutionary drug delivery system designed for oral administration of pharmaceuticals, developed using transdermal patch technology⁶. A thin oral film is inserted into the patient's mucosal tissue or tongue as part of the delivery technique. When moistened with saliva, it rapidly hydrates and adhesive to the application site. The drug is then liberated for mucosal absorption as it quickly dissolves and disintegrates. Film formers such as hydroxy propyl cellulose, methylcellulose, polyvinyl alcohol or PVP, maltodextrin, chitosan, sodium carboxy methyl cellulose, and natural gums are used to manufacture films^1,7.

Natural remedies are the most favorable way to provide treatment for various diseases without any side effects^8,9. The Panax ginseng plant, which is a member of the Araliaceae family, is regarded as among the most significant medicinal plants that have been used for thousands of years, especially in East Asia¹⁰. There are triterpene saponins known as ginsenosides that can be found in ginseng. These ginsenosides are the well-known bioactive part of ginseng. The steroidal nature of these substances gives them a wide range of pharmacological effects. They exhibit a range of antifungal, antiviral, antibacterial, antioxidant, and anti-inflammatory properties. They have exhibited therapeutic potential in the treatment of hypertension, stress, and neurological disorders^11,12.The pharmacokinetics parameters of Ginseng saponin compounds have been established by diverse clinical and in-vivo studies. However, the pharmacokinetic activities of ginseng and ginsenosides are uncertain due to their various chemical structures^11,13,14.

In spite of the fact that ginsenosides have significant pharmacological properties, research has indicated that oral administration of ginseng saponins results in minimal absorption and the low oral bioavailability. Additionally, these saponins undergo substantial metabolism in the gastrointestinal tract and have a low membrane permeability^11,15. Research studies conducted by Odani T et al.¹⁶,, ginsenosides orally administered to rats following pharmacokinetic study were found to have an oral bioavailability of less than 5%. Only 3.29% of Rg1 and 0.64% of Rb1 are found in rat serum, Rb1 levels stay steady for three days after oral ingestion, however Rg1 levels disappear within 24 hours^16,17 The unfavorable physicochemical characteristics of ginsenosides including insufficient transmembrane permeability across biological membranes, poor solubility in water, rapid metabolism within the body, and instability in gastrointestinal fluid, causes low bioavailability problems¹⁵. Furthermore, there are numerous approaches to improve the ginsenoside bioavailability. The targeted delivery of ginsenosides can be achieved by firstly dissolving and then protecting from physiological factors including low pH and enzymes in the gastrointestinal tract. Mouth Dissolving film is an alternative approach to bypass the problems associated with low oral bioavailability of ginseng^12,18–21.

The purpose of the research is to overcome the bioavailability problems associated with ginseng, by preparing its fast mouth-dissolving film using a variety of polymers by solvent casting method, as it may be further used to cure various diseases including hypertension, stress, neurological diseases, and respiratory problems.

MATERIALS AND METHODS:

Material:

Ginseng was acquired from Yarrow Chem Pvt Ltd, Mumbai. Polyvinyl alcohol was obtained from Loba Chemie Pvt. Ltd. HPMC E-15, and HPMC E-5 were supplied by Central Drug House (P)Ltd. New Delhi, Guar gum was obtained from Sisco Research Laboratories Pvt. Ltd. Maharashtra India. All the other reagents and chemicals were of analytical grade and utilized without modification.

Preformulation Studies:

Solubility:

The solvents, including distilled water, and a phosphate buffer solution PBS (pH 6.8), were used to determine the degree to which ginseng was soluble¹².

FTIR Analysis:

To determine the drug identification and drug-excipient compatibility, FTIR spectroscopy was used. In FTIR analysis, distinctive peaks were scanned from 4000-650 cm^{-1 12}.

Preparation of Ginseng Mdfs Using Solvent Casting Method:

Firstly, the drug along with all excipients is accurately weighed for different formulations as mentioned in Table 1. For solution A, all the polymers including HPMC E-5, HPMC E-15, and Guar gum were dispersed in distilled water to obtain a solution with continuous stirring. Ginseng was mixed with the above polymer solution and stirred to achieve a homogenous solution. In the other beaker for solution B, an appropriate amount of citric acid and sodium saccharin as mentioned in Table 1. was added to distilled water. Glycerol or PEG-400 was also added as a plasticizer to this solution. After that, solution B was steadily stirred into solution A to achieve a homogenous film-forming solution. The film solutions were transferred into dry and clean petri plates. The drying process was conducted in a hot air furnace at 45°C for 24hours. After that, the petridish was removed and allowed to settle to room temperature. One side of the petridish was inscised slightly to allow the film to be gently peeled using using a surgical scalpel. In order to minimise moisture penetration, tiny films measuring 2×2cm² were cut from a larger medium and initially packed in aluminium foil, followed by a sealed polythene bag. The resulting films were then assessed ^5,22,23.

Table 1: MDF formulations table.

S. No.	API and Excipients	F1	F2	F3	F4	F5	F6	F7	F8	F9
1.	Ginseng	20 mg	20 mg	20 mg	20 mg	20 mg	20 mg	20 mg	20 mg	20 mg
2.	HPMC E15	200 mg	150 mg	200 mg	-	-	-	-	-	-
3.	HPMC E5	-	-	-	200 mg	150 mg	200 mg	-	-	-
4.	Guar gum	-	-	-	-	-	-	100	150	200
5.	Sodium starch glycolate	40 mg	40 mg	40 mg	40 mg	40 mg	40 mg	40 mg	40 mg	40 mg
6.	Croscarmellose sodium	-	40 mg	40 mg	-	40 mg	40 mg	40 mg	40 mg	-
7.	Citric acid	20 mg	20 mg	20 mg	20 mg	20 mg	20 mg	20 mg	20 mg	20 mg
8.	Sodium saccharin	30 mg	30 mg	30 mg	30 mg	30 mg	30 mg	30 mg	30 mg	30 mg
9.	Glycerol	0.4 ml	0.4 ml	0.4 ml	0.4 ml	0.4 ml	0.4 ml	0.4 ml	0.4 ml	0.4 ml
10.	PEG -400	0.4 ml	0.4 ml	0.4 ml	0.4 ml	0.4 ml	0.4 ml	0.4 ml	0.4 ml	0.4 ml

*Amaranth, distilled water, and Ethanol as per quantity sufficient.

Evaluation of Film:

Physical Characterization:

Visual examination is a widely used method for determining the physical qualities of a substance, such as its thickness, fragility, peeling ability, transparency, tack property, surface uniformity, and film-forming capability^22,24.

Weight and Thickness:

The weight of all films (4cm²) was measured using a digital weighing balance. A Vernier caliper was used to measure the thickness of all the films. To determine the thickness of the film, measurements were taken from the three sides of the film, which are the uppermost side, the middle side, and the outermost side. The thickness and the weights of the film were measured by taking a small portion i.e. (4cm²) from a single film^25,26.

pH of the Surface:

Surface pH is a method that determines the pH value of an individual mouth-dissolving film. It was done by placing a single strip into a beaker consisting 1mL of distilled water. Once the film gets moist then its moist portion comes in contact with the pH meter electrode. The pH value then further indicates the film whether is acidic basic. pH of film is considered an important factor as its deviation may directly result in causing oral mucosal irritation^27,28.

Moisture Content:

The preweighed films are kept in the desiccators containing calcium chloride for more than 24 hrs at 40°C. The weight of the film was noted until it got constant and final weight was noted. The deviation between the initial and final weight used to calculate the percentage of moisture content^29,30.

Percentage Drug Content:

A film with a size of 2cm² × 2cm² was cut and placed in a 10ml solution of pH 6.8 PBS. 1ml sample from the petri dish was taken and properly diluted with PBS. At 201nm, the absorbance was determined using UV-Vis spectroscopy. The studies were repeated three times for each formulation of strips, and the average data were recorded^29,31.

Percent Elongation:

Strain is defined as the ratio of a film's initial dimensions to its distortion. When a material is subjected to tensile forces, it experiences an increase in length until it ultimately fractures. This phenomenon is referred to as elongation. It is an important factor to consider when evaluating a film's mechanical behavior and performance. The importance of elongation is its capacity to offer significant information regarding the ductility and strength of a material. The film generally increases in length as the plasticizer concentration increases. The Percentage elongation was calculated by using the formula mentioned below ^29,31.

Percentage elongation (%E) = [ L – L0] x 100 / L0

where L = final length and L0 = initial length.

Folding Endurance:

The brittleness of the film was evaluated by the use of the folding endurance testing method. It was determined by repeatedly folding the film until it broke. This test is used to evaluate the strength of films to survive repetitive bending, folding, and creasing^7,31.

Disintegration Time:

Petri plates method was used. A film size (2X2 cm²) was cut and dipped into the petri dish containing distilled water. The disintegration time refers to the point at which the film melts or entirely disintegrates^7,32.

In Vitro Drug Dissolution Test:

In-vitro, drug dissolution test was examined for different formulations by using a PBS (pH 6.8). The USP-type dissolution apparatus II (paddle type) was used to conduct the dissolution study at 37ºC±0.5ºC at 50rpm. Each film measuring (4 cm² of each) was positioned on a sieve mesh made of stainless steel with a 700μm sieve opening. Dissolution media was poured over the film sample that was positioned on the sieve. At regular time intervals (5mins) samples were taken out and filtered through Whatman filter paper of poresize 0.45μm. Withdrawn samples were examined using a UV-visible spectrophotometer (Shimadzu UV-1900i) at 201nm. After removing the samples, an equivalent volume of the blank dissolution medium was added to maintain the sink condition. Using a standard calibration curve that had been previously acquired by experiments the absorbance values were translated into concentration^24,29.

Kinetic of Drug Release:

The DD solver software was employed to analyze the drug release kinetics of the optimized formulation. Various kinetic models, including the Higuchi model, Hixon-Crowell model, Korsmeyer-Peppas model, first order, and zero order, were applied to the data from the drug release study. The model that best characterized the drug release pathways was selected based on its Model Selection Criteria (MSC) value, greatest R2 value, and least sum of square residual (SSR)^33,34

RESULTS AND DISCUSSION:

Preformulation Studies:

Solubility:

Ginseng solubility was tested in distilled water and a pH of 6.8 PBS. Ginseng is practically insoluble in distilled water and sparingly soluble in pH 6.8 PBS.

Melting Point:

The capillary method was employed to determine the melting point of ginseng in a triplicate manner. The melting temperature of ginseng was found to be 200ºC.

FTIR:

It was observed that the FTIR spectrum of pure drug Ginseng exhibited band shifts as well as fluctuations in the relative strength (absorbance) of bands, particularly at 3400, 2900, 1300, 1600, and 1000 cm^-1. At 3416.41 cm^-1, 2900.13 cm^-1, and 1639.39 cm^-1 spectrum represents -C-H, -CH₂-, and C=O groups stretching vibratuons respectively. The valley at 1370.17 cm⁻¹ indicates the stretching vibration of symmetrical COO groups. C-O-C groups exhibit characteristic bands in the 1221.01- 846.51 cm^-1 range, with the highest band at 1022.98 cm⁻¹ due to alcohol hydroxyl group vibration³⁵. The FTIR spectrum of the drug-polymer physical mixtures did not demonstrate any interaction or incompatibilities between them. The formulation (F3) that was optimized for the FTIR spectrum exhibited all of the principle characteristic peaks, which indicated the presence of Ginseng and the absence of any drug-excipient incompatibilities. Figure 1 shows the FTIR spectra of Ginseng, a drug-polymer and optimized formulation.

Figure 1: FTIR spectrum of drug, physical mixtures of drug and polymer and optimized formulations

Physical Characterization of Film:

Physical characterization by visual examination yielded the following results. The films were equally colored with no color migration as shown in figure 2. The increased quantities of HPMCE 5, HPMCE 15, guar gum, and polymer blend may contribute to the enhanced film thickness. All formulations formed films, were non-tacky, thin, flexible, simple to peel, and had flat surfaces on both sides.

Figure 2: Formulated Mouth Dissolving Film of Ginseng

Thickness and Weight:

The obtained film has a thickness in the range of 0.235 – 0.284mm. A thickness measurement found that the thickness of the oral dissolving film increased in proportion to the polymer concentration. The weight of all films was summarised in Table 2. The weights of the films were between 2.23 and 4.57gm.

Table 2: Thickness, Weight, Surface pH, Folding endurance, and Disintegration parameters of tablet

Formulations	Thickness (mm)	Weight (mg)	Surface pH	Folding endurance (count)	Disintegration time(min)
F1	0.248	3.34	6.45	78	8 min
F2	0.245	2.23	6.20	78	5 min
ssF3	0.250	3.21	6.24	88	6 min
F4	0.238	4.57	6.63	60	8 min
F5	0.235	4.21	6.84	58	6 min
F6	0.236	3.07	6.12	56	7 min
F7	0.256	4.22	6.22	52	7 min
F8	0.264	4.01	6.19	58	8 min
F9	0.284	3.23	6.12	59	8 min

pH of the surface:

The surface pH of formulations of ginseng was found between 6.12 to 6.84, which is near the neutral pH. It can be concluded that the films are more palatable for the patients without any irritation to the oral mucosa.

Moisture Content (%):

The weight of all mouth-dissolving films of ginseng was noted. The films were then placed in the desiccators with calcium chloride for 24hours at 40°C. The percentage moisture content for all formulations was found to be between 3.24 and 4.56%.

Folding Endurance:

Folding endurance reveals the fragility of the film. It was shown that the folding endurance value was affected by the amount, and type of film former and plasticizers. On increasing the amount of polymers and plasticizers, the folding endurance of film also increases as shown in formulation F3 with a folding endurance of 88.

Percent Elongation:

The percentage elongation testing indicates the elasticity of the film and also its strength to withstand the external pull. The results indicated that optimized formulation (F3) demonstrated a good % elongation of 92.12 cm %. The film generally increases in length as the concentration of plasticizer increases, due to a reduction in intermolecular forces and an increase in chain mobility of the plasticizer. The table 3 represents the results of percentage moisture content, percentage elongation and percentage drug release of all formulations F1-F9.

Table 3: Moisture Content, Percentage elongation and percentage drug content

Formulations	Moisture Content (%)	Percentage Elongation (cm %)	Percentage Drug Content (%)
F1	3.42	78.36	91.63
F2	3.24	85.23	90.32
F3	3.64	92.12	94.52
F4	3.85	62.85	90.08
F5	3.26	72.65	90.56
F6	3.45	82.36	89.56
F7	4.28	57.26	89.32
F8	4.56	58.26	87.23
F9	3.92	68.98	86.23

Percentage Drug Content:

According to the content uniformity studies, which show reproducibility techniques, every fast-dissolving oral film contained nearly the same amount of medication. The drug content in the films was assessed three separate cuts were found to have the values ranging from 86.23 to 94.52% the formulation F3 displayed the highest drug content of 94.52%. The films were determined to satisfy the content uniformity requirements under the USP specifications, there was a good content uniformity across the films evidenced by the lack of significant differences in drug content.

Disintegration Time:

Every formulation had a disintegrating time between 5 to 8 min. The optimized formulation (F3) was found to have a disintegration time of 5 min, showing a rapid disintegration for a fast onset of action.

In-Vitro Drug Release:

The percentage of drug release in all the formulated films F1 to F9 ranges from 59.62% to 90.89%. In total, 9 different fast disintegrating formulations of ginseng were prepared using film-forming polymers including HPMC (E15, and E5), and Guar gum, with or without Sodium starch glycolate and Croscarmellose sodium as a fast disintegrating agent. The formulations from F1 to F3 prepared using HPMC E15 significantly showed higher drug release within 15 minutes. The formulations from F4 to F6 prepared using HPMC E5 showed slightly higher than F7, F8, and F9 prepared from Guar gum. The graphs are depicted in Figure 3. Among the formulation tested optimized formulation (F3) demonstrates the highest Percentage of drug release 90.89 % within a brief period of 15 min compared to formulations to alternative ones.

Figure 3: Percentage Drug release of Ginseng Film in Phosphate buffer pH 6.8

Kinetic of Drug Release:

The drug release kinetics for the optimized formulations (F3) was determined using the DD Solver software. Each model’s correlation coefficient (R2) and the sum of square residuals (SSR) value were computed and Table 4 displays the results. The optimal formulation was based on the Korsmeyer-Peppas model which posses the lowest SSR value 15.6894 and highest R2 value 0.9971 and adjusted 0.9964. The model selection criteria (MSC) was maximum (4.6401) for the Korsmeyer-Peppas model, among all the models evaluated. Therefore, this model best describes the characteristics of drug release³⁶.

CONCLUSION:

In this work, the mouth-dissolving film of Ginseng was successfully prepared using two grades of HPMC(E-5 and E-15) and guar gum to form a mouth-dissolving film. All the polymers had excellent physicomechanical and dissolution characteristics. According to FTIR results, no incompatibility was identified between drugs and polymers. The films were found to be transparent and removed easily from Petri plates without changing homogeneity, colour, or smoothness. Among the 9 formulations, F3 has shown significantly high drug release 90.89%. Ginseng mouth dissolving films may give fast action which increases the bioavailability. Mouth-dissolving film provides better patient compliance in terms of ease of administration and therapeutic effectiveness compared to commercial formulations such as instant release and orally disintegrating tablets.

AUTHORS CONTRIBUTIONS:

RD and NK do experimental work, and manuscript writing. The manuscript is conceptualized, revised, and reviewed by YA. The research study was supervised, by YA, NN, and VJ.

CONFLICT OF INTEREST:

None.

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Received on 28.06.2024 Revised on 10.11.2024

Accepted on 18.02.2025 Published on 02.08.2025

Available online from August 08, 2025

Research J. Pharmacy and Technology. 2025;18(8):3684-3690.

DOI: 10.52711/0974-360X.2025.00530

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Creative Commons License.

Fitting Release	R²	R² adjusted	SSR	MSC
Zero-order reaction	0.9898	0.9898	54.6922	3.7246
First-order reaction	0.9618	0.9618	205.0614	2.4031
Higuchi model	0.9276	0.9276	388.9723	1.7629
Korsmeyer-Peppas model	0.9971	0.9964	15.6894	4.6401
Hixon-Cornwell model	0.9810	0.9810	102.2236	3.0992