N.T.V.S institute college of pharmacy, Nandurbar, India.
This study focused on the successful formulation of orally dissolvable films (ODFs) of Venlafaxine using the solvent casting method. HPMC E15 and Gellan gum were employed as film-forming polymers at various concentrations (25%, 30%, and 35%). The optimized formulation (F13), which utilized equal proportions of HPMC E15 and Gellan gum (25%), demonstrated superior drug release rates, stability, and overall performance compared to formulations with individual polymers (F2 and F5). F13 also provided advantages such as rapid onset of action, increased bioavailability, avoidance of first-pass metabolism, and reduced side effects, contributing to enhanced patient compliance, particularly among pediatric and geriatric populations. The biocompatibility, biodegradability, and non-toxicity of Gellan gum, along with its cost-effectiveness, make it a suitable natural polymer for ODFs. This study concluded that the combination of HPMC E15 and Gellan gum is ideal for developing Venlafaxine ODFs, offering a promising, patient-friendly dosage form with potential for large-scale production. These findings highlight the potential of natural polymers like Gellan gum in improving drug delivery systems and enhancing therapeutic outcomes.
The oral route of administration has long been favored by medical practitioners and manufacturers over other routes such as parenterals, topical, rectal, and vaginal due to its high patient acceptance. This preference is largely attributed to the ease of administration, convenience, and cost-effectiveness associated with oral delivery. The oral cavity offers a unique environment that makes it an attractive site for drug delivery. Over the years, there has been significant progress in oral solid drug delivery systems, evolving from traditional tablets and capsules to more advanced formulations like modified-release dosage forms and, more recently, fast-dissolving dosage forms (see Fig. 1). The challenge of swallowing solid oral dosage forms has driven the development of mouth-dissolving drug delivery systems, which address this limitation by allowing medication to dissolve quickly in the mouth, thus improving patient compliance and overall effectiveness. In the empire of psychiatric care, the ability to rapidly and effectively manage acute episodes is paramount. Venlafaxine Hydrochloride, a potent serotonin-norepinephrinere reuptake inhibitor (SNRI), has proven efficacy in treating various mood disorders, including major depressive disorder and generalized anxiety disorder. However, traditional oral delivery methods can be slow and cumbersome, potentially delaying crucial therapeutic intervention during emergencies. To address this challenge, we introduce a groundbreaking approach: Rapid-Release Oral Films for Emergency Psychiatric Intervention. This innovative formulation is designed to provide a swift onset of therapeutic effects, crucial for stabilizing patients during acute psychiatric episodes. Unlike conventional tablets or capsules, these ‘
Figure 1: Rapid-Release Oral Films for Emergency Psychiatric Intervention.
oral films dissolve quickly in the mouth, allowing for near-instantaneous absorption of Venlafaxine Hydrochloride into the bloodstream. This rapid dissolution and absorption facilitate a more immediate response, potentially reducing the onset time of therapeutic effects and improving patient outcomes in urgent situations. The development of this novel formulation involves advanced film technology and precise drug delivery systems, ensuring that the Venlafaxine Hydrochloride is both effective and safe. This approach not only enhances the speed of treatment but also offers ease of use and improved compliance, especially in scenarios where immediate intervention is critical. By integrating this fast-dissolving oral film technology into emergency psychiatric care, we aim to provide a more responsive and efficient solution for managing acute psychiatric conditions, ultimately enhancing patient well-being and treatment efficacy. Depression is a mood disorder characterized by persistent feelings of sadness and a loss of interest in previously enjoyable activities. Also known as major depressive disorder or clinical depression, it affects how individuals feel, think, and behave, and can lead to a range of emotional and physical issues. While physical health problems can sometimes trigger depressive symptoms, depression can also be part of a more complex psychiatric condition.
There are several types and sub types of depression, each with distinct features:
Major Depressive Disorder (MDD):
This type involves severe symptoms that impact a person’s ability to work, study, sleep, eat, and enjoy activities they once f
ound pleasurable. MDD can occur as a single episode or recur multiple times throughout a person’s life.
Persistent Depressive Disorder (PDD): Formerly known as dysthymia, this condition is characterized by a chronic state of low mood lasting for at least two years. It is less severe than major depression but can significantly impair daily functioning.
Seasonal Affective Disorder (SAD):
This subtype is related to seasonal changes, typically worsening in the winter months when there is less natural sunlight.
Psychotic Depression:
This form of depression includes symptoms of psychosis, such as hallucinations or delusions, in addition to the typical depressive symptoms.
Bipolar Disorder:
While not exclusively a depressive disorder, bipolar disorder includes episodes of major depression alongside periods of mania or hypomania. Understanding these variations helps in tailoring effective treatment strategies and improving outcomes for individuals affected by depression.
Figure 2: There are several types and sub types of depression, each with distinct features.
Treatments and Drugs:
Medications and psychological counseling (psychotherapy) are very effective for most people with depression. Your primary care doctor or psychiatrist can prescribe medication store live symptoms. However, many people with depression also benefit from seeing a psychologist or other mental health professional.
Table 1: Classes of Anti-Depressant Drugs:
MATERIALS AND METHOD:
A sample of Venlafaxine HCl for research purposes was obtained from Alembic Pharmaceuticals, located in Vadodara, Gujarat, India. Gellan, HPMCE15, PEG400, Pectin, Aspartame, Tween80, Citric acid chemicals were procured from LOBA Chemie Private Limited situated in Mumbai. All solvents and chemical working in the research be of analytical reagent (A.R.) grades, assuring difficult quality standards through the experimentations.
Figure 3: UV-Visible spectrophotometer Venlafaxine HCl lambda max at 225 nm.
Figure 4: Linearity range of Venlafaxine HCl.
A sample of Venlafaxine HCl was obtained from Alembic Pharmaceuticals, Vadodara, Gujarat, India, for research purposes. The identity of the sample was confirmed using UV spectroscopy. Venlafaxine HCl drug solution in Ph 6.8 (Phosphates buffer) was scanned using UV Spectrophotometer between the range 210-400nm using pH 6.8 as blank and the maximum absorbance (? max) was found at 225 nm.
Evaluation of films:
Thickness:
The thickness of all formulations F1-F15 was found by using Vernier caliper and the results were shown in the table no. 02:
Table 2: Determination of Thickness for Different formulations of Venlafaxine films (F1-F15):
Each data represents Mean ±SD (n=3)
The thickness of formulations F1 to F15 ranged from 46-52?m. All formulations showed film thickness between 5-200?m, complying with previous limits.
Folding Endurance:
Three films from each formulation were cut using a sharp blade. Folding endurance was measured by repeatedly folding a small strip of film at the same spot until it broke. The number of folds without breaking indicated the folding endurance. The mean values from three readings were then calculated and results were shown in the table no. 03:
Table 3: Determination of folding endurance or Different formulations of Venlafaxine films (F1-F15)
Each data represents Mean ±SD (n=3)
The folding endurance values of formulations F1 to F15 ranged from 100-170. All formulations demonstrated folding endurance values within the acceptable limit of 100-150.
Surface pH of Films:
The surface pH of the films was tested to assess potential side effects from pH changes in vivo, as acidic or alkaline pH could irritate oral mucosa. Each film was moistened with 1.0 mL of distilled water, and the pH was measured by placing a pH meter electrode on the film surface after 30 seconds. The average pH of three readings for each formulation was recorded, and standard deviation was calculated. The surface pH of all films was found to be within the acceptable range of 6-7.
Table 4: Determination of Surface pH for Different formulations of Venlafaxine films (F1 –F15):
Each data represents Mean ±SD (n=3)
Weight Variation:
Weight of 2 cm × 2 cm 2 film from different batches was weighed, and variation was calculated using electronic weighing balance.
Table 5: Determination of Weight variation for different formulations of Venlafaxine films (F1-F15):
Each data represents Mean ±SD (n=3)
From the results depicted in Table 5,it can be inferred that variation in the weight was in prescribed limits.
Disintegration Test:
The results of disintegration time are given in Table 6. These results indicated that the F13 formulations disintegrated faster than the F3, F15 formulations.
Table 6: Determination of disintegration time for different Formulations of Venlafaxine films (F1-F15):
Each data represents Mean ±SD (n=3)
With the petri dish method F13, F3, and F15 formulations disintegrated/dissolved faster than the other formulations.
Drug Content Uniformity
Percentage of drug content for different formulations was calculated and the results were shown in the table 7.
Table 7: Determination of drug content uniformity for different formulations of Venlafaxine films (F1-F15):
Each data represents Mean ±SD (n=3)
Percentage of drug content of F13 was found to be 113% and was considered as best formulation compared to the other formulation. The formulations showed percentage drug content 85-113%. From the results obtained from the above formulations. The drug content of films should be complying with the limit as 85-110% as per IP specifications (IP 2007).
In-vitro drug release study:
The drug release studies were per formed using USP dissolution test apparatus type II (Paddle type) using phosphate buffer solution (pH 6.8).
Table 8 Determination of Percent cumulative drug released different formulations of Venlafaxine film (F1-F15):
Each data represents Mean ±SD (n=3)
Figure 5: Determination of in-vitro release of Different formulations of Venlafaxine fast dissolving film (F8-F15).
From the study, it was concluded that the formulation prepared with equal compositions of HPMC E15 and Gellan Gum (F13) enhanced the drug release rate.
Compatibility Studies:
Table 9: Compatibility Studies of Venlafaxine HCl with Excipients:
From above result we can conclude that all excipients is compatible with Venlafaxine HCL.
FT-IR Compatibility Study:
The compatibility study between drug and the carriers was carried out using FT-IR spectrometer. The peak numbers of the drug exhibiting O-H, C-H, C-C, C-O, N- H, C-N stretching was observed and is depicted as below:
Table 10: Comparison of the peak of functional groups of Venlafaxine HCl observed in IR spectra of compatibility studies:
The physical mixture of Venlafaxine and excipients was analyzed using FTIR to detect any potential interactions. The results showed no significant appearance or disappearance of characteristic drug peaks, confirming the absence of chemical interactions between Venlafaxine and the excipients. As a result, the excipients Gellan, HPMC, and Pectin, which were found to be compatible with Venlafaxine, were selected for further formulation development
Stability Data: Stability studies were done according to ICH guidelines. The stability studies were carried out on the optimized satisfactory formulations F13 as per ICH guidelines. The optimized formulation batch F13 was sealed in aluminum foil packaging and kept in humidity chamber at fixed temperature and humidity. Here stability study was carried out in accelerated conditions at 40 ± 20 C and 75 ± 5% RH for 1 month.
Table 11: Evaluation Batch F13 after one month:
Batch F13 maintained its physical integrity, with minimal changes in folding endurance, surface pH, and assay after one month of storage, indicating good stability.
Each data represents Mean ±SD (n=3)
Percent Cumulative Drug Release of Formulation F13: The drug release profile of Batch F13 showed minimal variation after one month. At 5 minutes, the cumulative drug release was 98.42% initially and 97.75?ter one month, demonstrating consistent drug release over time with slight fluctuations across earlier time points. From the above stability data at 40°C/ 75% RH, shows that there was no significant difference in ?R of the formulation F13 before and after a month results. This concluded that the optimized formulation has sufficient
Percent Cumulative Drug Release of Formulation F13: The drug release profile of Batch F13 showed minimal variation after one month. At 5 minutes, the cumulative drug release was 98.42% initially and 97.75?ter one month, demonstrating consistent drug release over time with slight fluctuations across earlier time points. From the above stability data at 40°C/ 75% RH, shows that there was no significant difference in ?R of the formulation F13 before and after a month results. This concluded that the optimized formulation has sufficient stability at 40°C and 75% RH and extrapolated that formulation was stable at room temperature. So, the formulation after one month was found to be stable.
RESULT AND DISCUSSION:
In this study, orally dissolvable films (ODFs) of Venlafaxine were successfully formulated using the solvent casting method. HPMC E15 and Gellan gum were employed as film-forming polymers at different concentrations (25%, 30%, and 35%). The optimized formulations were developed by combining HPMC E15 and Gellan gum, with the combination formulation (F13) demonstrating superior results compared to formulations with individual polymers (F2 and F5). The use of the solvent casting method proved to be highly effective for ODF preparation. The optimized formulation (F13), which contained equal proportions of HPMC E15 and Gellan gum (25%), showed enhanced drug release rates and improved stability. These films were found to be highly beneficial in terms of patient compliance, particularly for pediatric and geriatric populations. Additionally, F13 provided advantages such as avoidance of first-pass metabolism, rapid onset of action, increased bioavailability, and reduced side effects. The overall stability of the formulation was also confirmed. Moreover, the study concluded that Gellan gum, either alone or in combination with HPMC E15, is a suitable natural polymer for ODF formulations. Its biocompatibility, biodegradability, non-toxicity, and cost-effectiveness make it an ideal choice for large-scale production. Therefore, the findings suggest that natural polymers like Gellan gum can be effectively used in the formulation of Venlafaxine ODFs, offering a promising and patient-friendly novel dosage form.
CONCLUSION:
The study successfully developed Venlafaxine ODFs using HPMC E15 and Gellan gum via solvent casting. The optimized formulation (F13), with equal concentrations of both polymers, showed enhanced drug release, stability, and patient compliance. The combination of natural, non-toxic, and cost-effective polymers makes this method ideal for large-scale production of ODFs with increased bioavailability and reduced side effects.
CONFLICTS OF INTEREST
The authors affirm that they have no conflicts of interest to disclose.
FUNDING
No funding applicable.
DECLARATION OF COMPETING INTEREST
I hereby declare that the research work presented in this article is original and has been carried out by me. It has not been submitted to any other journal for consideration of publication. All sources of information used in this study have been duly acknowledged. Furthermore, I take full responsibility for the accuracy of the data and the findings reported in this article.
ACKNOWLEDGMENT
I would like to express my sincere appreciation to the Principal of N.T.V.S institute college of pharmacy, Nandurbar, for his priceless mentorship and unwavering assistance. Additionally, I would like to extend my gratitude to the Principal of N.T.V.S institute college of pharmacy, Nandurbar, for their unwavering support and inspiration throughout this undertaking.
REFERENCE:
Vaishali R. Mahajan , Vasanti R. Mali , Rapid-Release Oral Films for Emergency Psychiatric Intervention: A Novel Formulation of Venlafaxine Hydrochloride, Int. J. of Pharm. Sci., 2024, Vol 2, Issue 10, 422-434. https://doi.org/10.5281/zenodo.13904697