Remember me
Nikita Kale*
, Sachin Kumar Jain and Sudha Vengurlekar
Faculty of Pharmacy, Oriental University, Indore (M.P.), India.
Corresponding Author E-mail: nikita.sohaney@gmail.com
Article Publishing History
Article Received on : 22 Feb 2025
Article Accepted on : 25 May 2025
Article Published : 16 May 2025
The study focused on developing and evaluating sublingual fast-dissolving films incorporating chlorpromazine HCl and haloperidol-loaded niosomes to enhance bioavailability and ensure sustained drug release. Using HPMC E15 and various excipients, films were prepared via solvent casting and exhibited desirable physical characteristics, including smooth texture, transparency, and optimal mechanical strength. In vitro and ex vivo results showed high drug release rates for both drugs, with chlorpromazine HCl releasing 90% in 2 hours and haloperidol 91% in 24 hours. Among the niosomal formulations, F7 showed the best performance. The findings highlight the effectiveness of the developed films in delivering drugs efficiently through the sublingual route.
KEYWORDS:Cumulative drug release; Fast Dissolving Film (FDF); Niosome; Sublingual film;
Download this article as:
Copy the following to cite this article:Kale N, Jain S. K, Vengurlekar S. Formulation, Development and Evaluation of Fast Dissolving Film Containing Niosomes for the Treatment of Psychosis. Orient J Chem 2025;41(3).
Kale N, Jain S. K, Vengurlekar S. Formulation, Development and Evaluation of Fast Dissolving Film Containing Niosomes for the Treatment of Psychosis. Orient J Chem 2025;41(3). Available from: https://bit.ly/3EVAg5B
Introduction
FDF technology has been used to market a variety of dosage forms. A number of processes have been used, including FDF tablets, tablet process modifications, centrifugal force application, temperature control, and freeze drying.1
Fast Dissolve Technology classification.
The following categories comprise Fast Dissolving Technology.
Compressed Tablet System
Freeze Drying System
Film strip/Fast Dissolving Film (FDF).
Fast dissolving film (FDF), commonly referred to as oral wafers, is a collection of thin polymeric films that are now attracting a lot of attention from the pharmaceutical sector. Many clients now embrace this innovative formulation for providing vitamins and self-care goods in particular. It is now being tested for prescription medications and licensed for over-the-counter medications for systemic distribution. [2]
Grouping
Three subtypes of oral patches are available:
Instant Disintegration,
Dissolution of Mucoadhesive,
Extended Release of Mucoadhesive
Benefits
The medicine dissolves and disintegrates quickly in the oral cavity because of its increased surface area.
Administering doses precisely
Adherence by patients
Secure and effective
Suitable and portable without requiring a measurement apparatus or water
A decrease in adverse effects due to the avoidance of first-pass hepatic metabolism and the administration of smaller doses.
Beneficial for people suffering from mental illnesses, motion sickness, dysphagia, and frequent vomiting.
Adaptable3
Drawbacks
The strip cannot contain a high dosage.
The range of acceptable medication goods is restricted.
The difficulty in achieving dosage uniformity
Application
Treat pain, allergies, sleep issues, and central nervous system diseases that call for quick medication absorption.
Breath strips
Vitamin and personal care product delivery
Topical application: mostly for antibacterial and analgesic ingredients
Gastric retentive dosage form: For compounds with a range of molecular weights that are both completely and weakly soluble in water
Diagnostic devices: These are used to separate several reagents or to provide an isolation barrier for sensitive reagents that allow regulated release when they come into contact with biological fluid.1
Methods
First, distilled water (DW) was used to dissolve a specified weight of HPMC E15. To the polymeric solution, add FD & C yellow no. 6, citric acid, menthol, and sodium saccharin, in that order.Following levigation with the necessary volume of glycerin, the computed quantity of cross-carmellose sodium was added to the polymeric solutions. Before adding cross-carmellose sodium, the necessary quantity of chlorpromazine hydrochloride was introduced straight to the polymeric solution and thoroughly dissolved in order to create medicated films (which include free medication). The chosen polymeric solution was carefully combined with a predetermined volume of the chosen niosomal dispersion (which corresponds to the necessary maintenance dosage of haloperidol) for the niosomal film. To stop the solvent from evaporating, the beaker was covered with aluminum foil and the final volume was adjusted with distilled water. A magnetic stirrer was used to agitate the distilled water for two hours at 700 RPM. A Petri plate that had been washed and dried was filled with 25 milliliters of distilled water. Before being evaluated, the film was taken off of the Petri plate and allowed to dry in a desiccator for 48 hours after the solvent had evaporated for 72 hours. To preserve the integrity and flexibility of the films, the patches were cut into 4 cm2 pieces and included 5 mg of haloperidol and 35 mg of chlorpromazine hydrochloride. They were then wrapped in aluminum foil and kept at room temperature in a dry location. Within a week of the film’s creation, an appraisal was conducted.4-7
Figure 1: Process flow chart for formulation of fast dissolving film.Click here to View Figure
Table 1: Formulation of Fast Dissolvingfilm
S. No. Ingredients Formulation Code NF1 NF2 NF3 NF4 NF5 NF6 NF7 NF8 NF9 1 Chlorpromazine HCl (mg) 35 35 35 35 35 35 35 35 35 2 Valsartan niosomal dispersion F7 (equi. mg) 5 5 5 5 5 5 5 5 5 3 HPMC E15 cps (% w/v) 1.75 1.75 1.75 2.25 2.25 2.25 2.75 2.75 2.75 4 Glycerin (% w/w of polymer) 15 20 25 15 20 25 15 20 25 5 Citric acid(%w/v) 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 6 Saccharin sodium (%w/v) 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 7 Cross carmellose sodium(% w/v) 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 8 FD &CYellow No. 6 Q.S Q.S Q.S Q.S Q.S Q.S Q.S Q.S Q.S 9 Menthol Q.S Q.S Q.S Q.S Q.S Q.S Q.S Q.S Q.S 10 Distilled water Upto 25 mlEvaluation parameters for Medicated film
The film must be flat, rigid, and free of edge crimping. The FDF strip needs to be sturdy enough to be handled by the customer without breaking and to be taken out of the unit-dose package. When inserted into the oral cavity, the film must also breakdown easily to release the active ingredient quickly. The fast-dissolving film’s mechanical characteristics are crucial in determining all of these factors. As a result, the rapid dissolving film’s mechanical characteristics are just as crucial as its rate of solubility. Thus, the following criteria were used to assess the created mouth dissolving films 8-10
Physical appearance
Through visual assessment, the physical appearance was verified.
Texture of surfaces
By touching the surface, the texture was verified.
Evaluation of mechanical properties (MP)
What degree of strain or tension a film can withstand during formulation, packaging, and transportation is determined by its melting point. Additionally, the film’s strength and elasticity are demonstrated, as measured by its tensile strength and elasticity upon break. The table that follows distinguishes the kind of polymer. 9
Table 2: Film’s Melting point
S.No. Polymer sort Tensile strength Elongation 1 Weak, Soft L L 2 Brittle, Hard M L 3 Soft, Hard M H 4 Hard, Tough H HL: Low; M: Moderate; H: High
A low elastic modulus, a high percentage of elongation at break, and moderate TS are characteristics of an acceptable film. Film MP, or film thickness measured with a digital micrometer, Digital Tensile Strength Strengthening Burst A test strip of 10 x 50 mm and devoid of any physical flaws or air bubbles was clamped between two clamps spaced 10 mm apart. The strip was pulled at a rate of 5 mm per minute while being measured. When the film broke, the mechanical property values were noted. Calculations did not include results from film samples that broke at the clamps rather than between them. For every film, measurements were performed three times. Three mechanical characteristics of the films were assessed: their tensile strength, percentage elongation, and folding durability. 11
Tensile Strength (TS)
The highest stress exerted at the point where the film specimen breaks is known as TS. The TS, which is expressed in force per unit area (N/mm2), was computed by dividing the greatest load at failure by the film’s native cross-sectional area. 10
Elongation percentage at break (% E)
The extension at the point of rupture of the specimen was divided by the starting gage length of the specimen, and the result was multiplied by 100 to determine the percent elongation at break (% E).
Folding Endurance (FE)
FE was carried out by repeatedly folding the film at the same spot until it broke. The value of folding endurance is determined by counting the number of times the film can be folded in the same spot without separating.
Study of in vitro disintegration
In a glass petridish, 25 milliliters of 67 mM phosphate buffer pH 6.8 were used to quantify the in-vitro DT (n=3) for each batch’s film. A 2 cm × 2 cm film sample was placed in 20 milliliters of artificial saliva. A magnetic stirrer was used to keep the medium somewhat stirred. The moment the film was fully dissolved in the saliva was recorded as DT. Attention was paid to the average of three values.12
Thick ness of film
A micrometer was used to measure each film’s thickness five times (at the center and four corners), and the average thickness was determined.
Uniformity of drug composition
Each cast film was dissolved in 100 mL of 67 mM phosphate buffer pH 6.8 after 4 cm2 (2 cm × 2 cm) patches were cut from various locations within the film to verify the consistency of the drug content. After filtering the resultant solution and diluting it further with 67 m M phosphate buffer pH 6.8, the absorbance was measured spectrophotometrically to ascertain the drug content %. At least three patches of each formulation underwent the same process, and the mean values and standard deviations were given.11
Surface pH
Three films of each formulation were let to come into contact with one milliliter of distilled water for an hour at room temperature, and the pH was then measured using a pH meter. By placing the electrode on the film’s surface and letting it equilibrate for a minute, the surface pH was determined.
Percentage of moisture loss
This test was also used to assess the films’ integrity after they were dry. Accurately weighed film was stored in a desiccator with fused anhydrous calcium chloride. The film was taken out and weighed after a day. The percentage of moisture loss was calculated using the formula below. 8-9
In Vitro Drug release study
The USP dissolution test equipment II (Paddle) was used to perform the in vitro release of chlorpromazine HCl and haloperidol from the prepared film. A stirring rate of 100 rpm and 900 mL of dissolving media kept at 37.0 ± 0.5°C were used. For 24 hours, each formulation was tested separately in 900 mL of 67 ml M phosphate buffer with a pH of 6.8. To keep the volume constant, 5 mL samples were taken out of the dissolving media at appropriate intervals and replaced with new medium. The quantity of medicines released in each sample was measuredspectrophotometrically at λmax 280 nm for chlorpromazine HCl and 247.5 nm for haloperidol following filtering and the proper dilution.13
Details of Dissolution Test
Device: USP Type II (Paddle)
The medium’s volume was 900 milliliters, and its temperature was 37 °C ± 0.5 0.
100 rpm paddle speed
67 ml of M phosphate buffer pH 6.8 with 0.5% SDS was employed as the dissolution media.
An aliquot of 5 ml is taken at each time interval.
Permeability investigation in vivo
For the improved formulation, permeability tests were conducted using a modified Franz diffusion cell with an internal diameter of 2.5 cm. The model membrane utilized was the sublingual mucosa of goats. Prior to mounting, the membrane was stabilized in order to extract the soluble components. The donor and receptor compartments were separated by the mucosa.27 ml of 67 ml M Phosphate buffer pH 6.8 was added to the receptor compartment, and the hydrodynamics were maintained by stirring with a magnetic bead at 50 rpm while the temperature was kept at 37 ̦ C ± 0.2 ̦ C. The mucosal surface that had been wet with a few drops of media was brought into close contact with a previously weighed 2×2 cm film. A single milliliter of 67 mM phosphate buffer (pH 6.8) was added to the donor compartment. To keep the sink condition, samples were taken out at appropriate intervals and replaced with the same volume of fresh medium. For haloperidol and chlorpromazine HCl, the cumulative percentage of drug penetration was measuredspectrophotometrically at 247.5 nm and 280 nm, respectively. 12-13
Residual solvent analysis
GC often uses the compendial approach to determine residual solvent. However, in our study, Class-3 Diethyl Ether was used to produce a maintenance dose-loaded Haloperidol Niosome. Based on the rationale presented in the Results and Discussion, this test is unnecessary because the quantity of diethyl ether in the optimized Niofilm formulation C1 was 28127 ppm.
Study of morphology
Surface texture and physical appearance were assessed by touch and eye inspection, respectively.
SEM, or scanning electron microscopy
SEM was used to examine the surface’s texture and shape. Cameras also took simple pictures of film. The film formulation was adhered on an aluminum stub using double-sided adhesive tape to create the samples for the SEM. The film samples were then randomly scanned and microphotographs were taken on different magnification and higher magnification was used for surface morphology,homogenicity of polymer and drug distribution and texture of film. The accelerator voltage was set at 30.0KV during scanning.
Separability
The best film from several first trial batches was chosen using in-vitro DT, which also assisted in choosing the kind of polymer for further research. The separability of the film was measured by how quickly it detached from the mold.12
Table 3: Film separability code
S.No. Film separability Code 1 Good ++ 2 Moderate + 3 Poor –Result and discussion
The results of all evaluation parameters of fast dissolving film formulations were shown in below tables:
Table 4: Evaluation parameter of film formulations
S. No. Formulation code Physical appearance and Surface texture Tensile strength (N/mm2) % Elongation* Folding endurance* 1 NF1 ** 3.55±0.122 56.43±1.20 148±2.34 2 NF2 ** 4.19±0.142 89.50±0.88 157±3.35 3 NF3 ** 5.10±0.098 92.34±0.14 160±1.87 4 NF4 ** 5.01±0.091 98.65±0.29 168±1.45 5 NF5 ** 5.53±0.119 176.45±0.45 177±2.04 6 NF6 ** 6.20±0.137 201.23±0.30 182±3.22 7 NF7 ** 6.27±0.155 102.25±0.75 185±1.23 8 NF8 ** 6.45±0.085 189.45±0.81 192±2.77 9 NF9 ** 6.76±0.121 208.34±0.91 220±3.78*All results are shown in mean±S.D.(n=3)
**Clear transparent, yellow color, non-sticky with as mooth surface
Table 5: Evaluation parameter of film formulations
S. No. Formulation code In Vitro Disintegration Time ( Sec.) CU Chlorpromazine HCl (% of label claim) * CU Haloperidol (% of lael claim)* 1 NF1 28±2.2 94.11±4.02 94.21±0.48 2 NF2 32±1.5 92.77±3.41 96.36±0.21 3 NF3 39±4.5 95.33±4.20 92.37±0.56 4 NF4 37±3.5 95.96±3.51 92.53±0.37 5 NF5 42±3.3 95.60±4.37 95.37±1.25 6 NF6 49±1.9 92.74±6.86 92.25±0.81 7 NF7 45±1.6 94.57±2.29 97.06±0.67 8 NF8 57±2.7 96.80±1.81 91.59±0.26 9 NF9 62±3.4 94.03±4.17 90.43±0.13CU: Content uniformity
*All results are shown in mean±S.D.(n=3)
Table 6: Evaluation parameter of film formulations
S. No. Formulation Code Thickness (µm)* Surface pH* % Moisture loss* 1 NF1 64.17±4.40 6.23±0.06 1.82±0.05 2 NF2 63.00±4.86 6.38±0.08 2.66±0.15 3 NF3 63.33±2.94 6.43±0.03 3.19±0.09 4 NF4 76.33±3.61 6.50±0.10 2.18±0.22 5 NF5 76.17±5.00 6.38±0.13 2.74±0.34 6 NF6 77.17±3.31 6.51±0.05 3.37±0.37 7 NF7 102.50±5.82 6.46±0.22 2.39±0.59 8 NF8 100.50±7.53 6.53±0.15 2.88±0.67 9 NF9 101.17±6.52 6.72±0.03 3.56±0.59*All results are shown in mean±S.D.(n=3)
Table 7: In-Vitro drug release of Chlorpromazine HCl from film formulations
S. No. Time % Cumulative drug release (Chlorpromazine HCl) NF1 NF2 NF3 NF4 NF5 NF6 NF7 NF8 NF9 1 0 0 0 0 0 0 0 0 0 0 2 5 47.06 49.1 49.56 48.65 50.13 50.87 50.98 51.36 52.98 3 10 55.84 54.71 53.12 51.23 56.41 57.41 56.84 57.86 59.64 4 15 59.7 60.12 57.41 56.21 62.24 63.59 60.27 64.51 65.24 5 20 65.48 66.41 64.1 63.54 69.55 70.12 68.34 72.36 73.02 6 25 72.54 73.64 70.33 70.98 74.68 75.65 73.1 76.99 79.35 7 30 78.98 81.12 79.58 78.66 82.54 81.26 80.67 83.54 85.21 8 35 89.54 88.96 90.32 85.94 89.03 90.23 89.64 89.14 92.35 9 40 96.47 97.13 95.64 93.15 94.21 95.64 93.55 96.55 98.81Table 8: In-Vitro drug release of Haloperidol from film formulations
S.no. Time % Cumulative drug release (Haloperidol) (Min) NF1 NF2 NF3 NF4 NF5 NF6 NF7 NF8 NF9 1 0 0 0 0 0 0 0 0 0 0 2 15 28.65 27.41 30.12 26.74 29.56 30.14 31.25 28.32 30.96 3 30 32.45 30.14 32.74 30.98 33.41 34.55 35.74 33.56 29.84 4 45 41.63 42.37 46.29 41.02 45.9 44.52 43.58 42.09 41.65 5 60 49.6 51.23 50.88 48.61 50.64 51.63 52.9 51.96 50.98 6 120 51.56 54.63 52.61 52.35 55.03 56.47 53.61 54.61 51.86 7 240 59.84 58.2 61.84 58.96 61.25 63.59 60.95 62.9 61.27 8 360 65.53 68.41 69.56 63.87 68.58 69.21 68.83 69.15 70.33 9 480 71.29 73.64 75.26 69.82 71.69 71.68 74.62 73.64 74.91 10 600 79.83 81.23 81.42 74.96 75.82 80.35 81.39 81.63 79.1 11 720 82.36 85.41 85.63 79.16 80.31 86.23 85.64 85.94 84.28 12 1080 92.24 89.67 94.57 88.54 86.54 91.54 95.63 90.87 92.34 13 1440 99.57 93.72 102.3 97.68 91.62 96.55 103.3 95.39 100.2Table 9: Ex-vivo permeability results of ChlorpromazineHCl and Haloperidol from Optimized formulation NF9
Time (Min) % Cumulative amount of drug permeated Cumulative amount of drug permeated per cm2 (mg) Chlorpromazine HCl Haloperidol Chlorpromazine HCl Haloperidol 0 0 0 0 0 5 48.59 – 0.662 – 10 52.65 – 0.717 – 15 60.21 25.61 0.82 5.122 20 69.85 – 0.951 – 25 73.96 – 1.007 – 30 80.24 30.47 1.093 6.094 35 85.67 – 1.167 – 40 90.12 – 1.227 – 45 – 39.65 – 7.93 60 – 46.18 – 9.236 120 – 51.96 – 10.392 240 – 59.12 – 11.824 360 – 62.59 – 12.518 480 – 69.75 – 13.95 600 – 72.83 – 14.566 720 – 79.91 – 15.982 1080 – 86.54 – 17.308 1440 – 91.27 – 18.254Inference
Physical appearance and Surface texture
The physical characteristics of all trial batches were clear, transparent, yellow, non-sticky, and smooth.
Strength in tensile
A representation of film strength is provided by the tensile strength. Tensile strength readings come in a range of 3.55±0.122 N/mm2 to 6.76±0.121 N/mm2. According to the findings, the film’s tensile strength increased as the polymer concentration increased.
Figure 2: Histogram of Tensile strength of formulations.Click here to View Figure
%Elongation
The film’s elasticity is indicated by the percentage elongation. Tensile strength findings vary from 56.43±1.20% to 208.34±0.91%. According to the findings, the percentage of film elongation increased as the polymer concentration increased.
Figure 3: Histogram of % Elongation of formulations Click here to View Figure
Folding endurance
The film’s brittleness is shown by folding endurance. Folding endurance results vary from 148±2.34 to 220±3.78. According to the findings, folding endurance rises with increasing polymer and plasticizer concentrations.
Figure 4: Histogram of Folding endurance of formulationsClick here to View Figure
In-Vitro disintegration time
The primary determinant of the amount of medication release in a shorter amount of time and a quicker commencement of effect is the in vitro disintegration time. The in vitro disintegration time values vary from 28±2.2 seconds to 62±3.4 seconds. The findings showed that, as the amount of polymer grew, the in-vitro disintegration time increased as well because the film became thicker. Because glycerin is hydrophilic, it slows down the wetting process, which eventually causes the in-vitro disintegration time to decrease as the amount of glycerin rises.
Figure 5: Histogram of In-Vitro Disintegration time of formulations.Click here to View Figure
Thickness
The thickness measurements vary from 63.00±4.86µm to 102.50±5.82µm. The findings showed that when the amount of polymer grew, thickness rose as well. The relationship between thickness and polymer is linear. Polymer optimization results in thickness control, which has an indirect impact on in vitro disintegration time. Glycerin and thickness do not appear to be correlated in any way.
Figure 6: Histogram of Thickness of formulationsClick here to View Figure
Contentuniformity(CU)
CU isalso predominantparameter foradministrationof precise dose inpatient. CU is solely dependent on the formulation process. The results of CU ranges between 92.74±6.86% of label claim to 96.80±1.81% of label claim for Chlorpromazine HCl and 90.43±0.13% of label claim to 97.06±0.67% of label claim for Haloperidol. From the results it was observed that all the formulation had > 90 % CU which does not leads to any problem. There were no any significant changes perceived with respect to polymer and plasticizer in formulations.
Figure 7: Histogram of Content uniformity-Chlorpromazine HCl of formulationsClick here to View Figure
Figure 8: Histogram of Content uniformity-Haloperidol of formulationsClick here to View Figure
Surface pH
The surface pH was determined to be near neutral, ranging from 6.23±0.06 to 6.72±0.03. This suggests that films may be more pleasant because they are less likely to irritate the sublingual mucosa.
Figure 9: Histogram of Surface pH of formulationsClick here to View Figure
%Moistureloss
The purpose of this test was to assess the films’ integrity when they were dry. The percentage of moisture loss ranged from 1.82±0.05% to 3.56±0.59%.
Figure 10: Histogram of % Moisture loss of formulationsClick here to View Figure
Conclusion
In the current study, fast-dissolving films containing chlorpromazine HCl and niosomes loaded with haloperidol were made and assessed. While the films were employed to improve the drug’s bioavailability through the sublingual route, niosomes were used to enable a prolonged release of the medication. Both the film and the niosomewere assessed independently using their own assessment criteria. First, nine batches of niosomes were prepared and assessed; of those nine batches, F7 was determined to be the optimum formulation. Tensile strength ranged from 3.55 to 6.76 N/mm2, while elongation percentage ranged from 56 to 208%. folding endurance between 148 and 220. Haloperidol and chlorpromazine HCl both had 94% and 96% in vitro drug release, respectively. The film’s thickness ranged from 64 to 101 µm. Haloperidol 100.2 percent and chlorpromazine HCl98.81% had the largest cumulative drug release, whereas surface PH ranged from 6.23 to 6.72 percent and moisture loss from 1.82 to 3.56 percent. These assessment parameters showed that the maximum ex-vivo permeability and percentage cumulative drug release were for chlorpromazine HCl 90% in 2 hours and haloperidol 91% in 24 hours. The improved formulation was identified as the ninth formulation with code NF9, and it was investigated for an ex-vivo permeability investigation.
Acknowledgement
The authors are highly thankful to OUI Oriental University, Indore for providing the necessary facilities for this research work.
Conflict of Interest
There is no conflict of interest.
Funding Sources
The author(s) received no financial support for the research, authorship, and/or publication of this article.
References
Kumar L. Rapidly dissolving felodipine nanoparticle strips-formulation using design of experiment and characterisation. Journal of Drug Delivery Science and Technology. 2020;60:1-5.
This work is licensed under a Creative Commons Attribution 4.0 International License.
Related Posts
Comments (0)