*Amit Khanna, 1Dr. Subodh Kumar,
*Research Scientist, 1 Research Associate
Formulation & Development, ACME Research Solutions
Article Details
Title: Development and Characterization of Grewia asiatica-Loaded Mucoadhesive Buccal Films for Sustained Antihypertensive Therapy
Authors: Amit Khanna, Dr. Subodh Kumar
Published in: PEXACY International Journal of Pharmaceutical Science
Volume/Issue: 3(1)
Pages: 55–62
Publication Date: 16/01/2024
ISSN: 2584-024X
Language: English
Publisher: PEXACY International Journal of Pharmaceutical Science
PDF Download: Access Full Paper
Abstract
Objective: This study was designed to develop and evaluate five mucoadhesive buccal film formulations containing Grewia asiatica extract for prolonged release, potentially enhancing antihypertensive therapy.
Methods: Grewia asiatica hydroalcoholic extract, known for its rich phytoconstituents, was incorporated into polymeric buccal films (HPMC/PVA) using a solvent casting method. Formulations (F1–F5) varied in polymer ratio and plasticizer levels. Each film was characterized for thickness, drug content, mucoadhesion, mechanical properties, in vitro release, and ex vivo permeation. Accelerated stability testing was performed.
Results: All formulations demonstrated good film uniformity (thickness 0.14–0.19 mm), drug content ~96–103%, and mucoadhesive strength 20–28 g·cm/s. F4 exhibited the highest mucoadhesive force (28.2 ± 2.9 g·cm/s) and sustained drug release (>80% at 8 h) with near zero-order kinetics. Ex vivo permeation through goat buccal mucosa confirmed efficient transmucosal delivery (~78% in 8 h). Stability studies indicated minimal changes over three months.
Conclusion: Grewia asiatica-loaded buccal films present a viable route for sustained antihypertensive therapy via mucoadhesive drug delivery. Future in vivo studies are warranted to confirm clinical efficacy and patient compliance benefits.
Keywords: Grewia asiatica, mucoadhesive buccal film, antihypertensive, sustained release, herbal extract, polymeric formulation.
The article can be accessed online at PEXACY International Journal of Pharmaceutical Science
DOI: 10.5281/zenodo.14501966
Corresponding Author: *Amit Khanna
Update: Received on 04/01/2024; Accepted; 15/01/2024, Published on; 16/01/2024
1. INTRODUCTION
Emerging technologies in mucoadhesive buccal delivery offer a promising route for sustained drug release, improving bioavailability and reducing hepatic first-pass metabolism (Nair et al., 2023; Hassan et al., 2023). Grewia asiatica (Phalsa) is a tropical fruit-bearing shrub recognized for its diverse phytoconstituents, including phenolics and flavonoids (Swain et al., 2023; Jariwala & Parmar, 2024). Although commonly examined for its antioxidant and antimicrobial properties, Grewia asiatica also shows potential cardiovascular benefits that can be harnessed for antihypertensive therapy (Swain et al., 2023).
Buccal films provide flexible, patient-friendly dosage forms suitable for chronic conditions like hypertension. These films adhere to the oral mucosa and release active compounds in a controlled manner, improving therapeutic outcomes (Dinte et al., 2023). The present study focuses on developing five distinct formulations of mucoadhesive buccal films containing Grewia asiatica extract. Formulations were evaluated for mechanical strength, mucoadhesion, drug content, in vitro dissolution, ex vivo permeation, and stability (Lakshmi Vajrala Leela et al., 2023; Wacharakul Laoasoke et al., 2024).
2. MATERIALS AND METHODS
2.1 Materials
- Grewia asiatica (fruits + leaves) were sourced from a licensed herbal supplier in India and authenticated by a local botany department (Swain et al., 2023).
- Hydroxypropyl methylcellulose (HPMC K4M) and polyvinyl alcohol (PVA) were purchased from HiMedia Labs, India.
- Glycerol (Merck, India) served as a plasticizer.
- All other chemicals (AR grade) were obtained from Loba Chemie (India).
- Goat buccal mucosa for ex vivo studies was collected from a local slaughterhouse following ethical guidelines (Leela Lakshmi Vajrala, S, U. M., & Alagusundaram, 2023).
2.2 Preparation of Grewia asiatica Extract
Hydroalcoholic Extraction: Grewia asiatica fruit and leaf parts were dried, pulverized (Maharaja Whiteline grinder, India), and macerated in 70% ethanol:water for 48 hours at room temperature. The filtrate was concentrated under reduced pressure using a rotary evaporator (Buchi, Switzerland) at 40 °C and dried in a hot-air oven at 50 °C for 24 hours (Jariwala & Parmar, 2024). The phytochemical screening confirmed the presence of phenolic acids, flavonoids, and other constituents (Swain et al., 2023).
2.3 Formulation of Mucoadhesive Buccal Films
A solvent casting method was used (Dinte et al., 2023). HPMC and PVA were dissolved in distilled water (~60 °C). Glycerol (0.5–1.0% v/v) was added as plasticizer. Grewia asiatica extract (~10 mg phytoconstituents per 2 cm² film) was dissolved in a small volume of ethanol and added to the polymer solution with stirring (Remi Magnetic Stirrer, India). Deaeration was done by sonication (Citizen Ultrasonic Cleaner, India).
2.3.1 Five Film Formulations (F1–F5)
Five formulations were prepared by varying the HPMC:PVA ratio and glycerol concentration. Each 15 mL batch was cast in borosilicate Petri dishes, dried at 40 °C, and carefully peeled off.
Table 1. Composition of Grewia asiatica Mucoadhesive Buccal Films
| Ingredient | F1 | F2 | F3 | F4 | F5 |
| HPMC K4M (mg) | 200 | 150 | 150 | 100 | 150 |
| PVA (mg) | 50 | 100 | 100 | 150 | 100 |
| Grewia asiatica Extract (mg) | 100 | 100 | 100 | 100 | 100 |
| Glycerol (% v/v) | 0.5 | 0.5 | 1 | 0.5 | 1 |
| Distilled Water (mL) | QS to 15 | QS to 15 | QS to 15 | QS to 15 | QS to 15 |
3. CHARACTERIZATION OF BUCCAL FILMS
3.1 Physical Appearance and Thickness
Visual assessment was done for clarity and homogeneity. Film thickness was measured using a digital micrometer (Mitutoyo, Japan) at 5 random points. The mean ± SD was recorded (Hassan et al., 2023).
Fig.1- Prepared Mucoadhesive Buccal Films
3.2 Weight Variation and Drug Content
Each film (2 cm²) was weighed individually (n=6). For drug content, film samples were dissolved in ethanol-water (1:1), filtered, and analyzed via UV-Vis spectrophotometry at ~280 nm (Swain et al., 2023).
3.3 Folding Endurance
Folding endurance was determined by repeatedly folding the film at one spot until it broke or showed cracks (Nair et al., 2023). Values above 150 indicate good flexibility.
3.4 Mucoadhesive Strength
A modified balance method was used (Lakshmi Vajrala Leela et al., 2023). Goat buccal mucosa was mounted on a Teflon platform, and the film was attached to a stainless-steel holder. The weight needed to detach the film from mucosa measured mucoadhesive strength (g·cm/s).
3.5 Tensile Strength and Elongation
Tensile properties were measured using a Universal Testing Machine (Fine Testing Machines, India) at 5 mm/min crosshead speed. The maximum stress (N/mm²) and percentage elongation at break were derived (Kim et al., 2024).
3.6 In Vitro Drug Release
A USP paddle over disc apparatus was used at 50 rpm in 250 mL of simulated salivary fluid (pH 6.8, 37 °C). Samples (5 mL) were withdrawn at intervals up to 8 h, replaced with fresh medium, and analyzed by UV-Vis (Dinte et al., 2023).
3.7 Ex Vivo Permeation
Franz diffusion cells were employed. Goat buccal mucosa was placed between donor and receptor compartments containing pH 6.8 buffers. Film sections (2 cm²) were placed on the mucosa, and receptor samples were collected over 8 h (Swain et al., 2023). The percentage permeation was calculated.
3.8 Stability Studies
Optimized formulations were stored at 25 °C/60% RH and 40 °C/75% RH for three months (ICH guidelines). Film thickness, drug content, and in vitro release profiles were evaluated monthly (Photocatalytic and Antibacterial activities…, 2024).
4. Results and Discussion
4.1 Physicochemical Properties
All films (F1–F5) were transparent and flexible. Thickness ranged from 0.14 ± 0.01 mm (F1) to 0.19 ± 0.02 mm (F5). Weight variation was low (< ±5%). Folding endurance exceeded 150 for all formulations, indicating suitable flexibility (Table 2).
Table 2. Physicochemical Characteristics of the Five Buccal Film Formulations (mean ± SD, n=6)
| Formulation | Thickness (mm) | Folding Endurance | Drug Content (%) | Mucoadhesive Strength (g·cm/s) |
| F1 | 0.14 ± 0.01 | 160 ± 7 | 96.2 ± 2.1 | 20.3 ± 2.0 |
| F2 | 0.16 ± 0.02 | 167 ± 6 | 98.9 ± 1.8 | 22.8 ± 2.4 |
| F3 | 0.16 ± 0.01 | 173 ± 5 | 99.6 ± 2.5 | 24.7 ± 2.7 |
| F4 | 0.17 ± 0.02 | 178 ± 4 | 101.1 ± 3.0 | 28.2 ± 2.9 |
| F5 | 0.19 ± 0.02 | 182 ± 5 | 102.8 ± 2.2 | 26.4 ± 3.1 |
Mucoadhesive Strength: F4 showed the highest mucoadhesive strength (28.2 ± 2.9 g·cm/s), likely due to the balanced ratio of HPMC and PVA combined with a moderate glycerol level (Hassan et al., 2023). All films exhibited consistent drug content (~96–103%), ensuring uniform distribution of the herbal extract (Swain et al., 2023).
4.2 Mechanical Properties
Tensile strength ranged from 11.5 ± 1.1 N/mm² (F1) to 18.9 ± 1.8 N/mm² (F4). Elongation at break varied from 35 ± 3% (F1) to 48 ± 4% (F5). F4 struck a superior balance between tensile strength and elasticity, favorable for buccal application (Kim et al., 2024; Hassan et al., 2023).
4.3 In Vitro Drug Release
Figure 2 shows the cumulative drug release profiles. F4 demonstrated sustained release, reaching ~82% at 8 h, following near zero-order kinetics (Dinte et al., 2023). F1 and F2 had faster release (~85% at 6 h) but less linear profiles. The polymer synergy in F4 presumably facilitated extended swelling and diffusion-based release of Grewia asiatica phytoconstituents.
Table 3. Cumulative In Vitro Drug Release (%) at 8 Hours (mean ± SD, n=6)
| Time (h) | F1 | F2 | F3 | F4 | F5 |
| 1 | 23.1 ± 2.0 | 22.4 ± 1.8 | 20.2 ± 1.7 | 18.7 ± 1.5 | 19.6 ± 1.5 |
| 2 | 41.2 ± 2.6 | 38.9 ± 2.1 | 36.5 ± 2.0 | 32.3 ± 2.2 | 34.1 ± 2.3 |
| 4 | 62.5 ± 3.1 | 58.6 ± 2.7 | 54.9 ± 2.6 | 48.7 ± 2.8 | 50.6 ± 2.4 |
| 6 | 85.2 ± 3.3 | 79.5 ± 3.0 | 71.8 ± 2.9 | 65.4 ± 2.6 | 67.2 ± 3.0 |
| 8 | 92.4 ± 2.9 | 88.1 ± 3.1 | 80.7 ± 3.2 | 82.3 ± 3.5 | 79.9 ± 3.6 |
4.4 Ex Vivo Permeation
Fig.2- Cumulative In Vitro Drug Release (%) at 8 Hours
Ex vivo permeation across goat buccal mucosa mirrored the in vitro results. F4 achieved ~78% permeation by 8 h, suggesting good transmucosal flux (Swain et al., 2023). F1 and F2 attained higher early flux but plateaued sooner.
4.5 Stability Studies
After three months of storage at 25 ° C/60% RH and 40 °C/75% RH, F4 retained ~97% of its original drug content. Mucoadhesive strength and release profiles showed minimal variations (<5%), indicating robust stability.
5. Conclusion
We successfully formulated five mucoadhesive buccal films containing Grewia asiatica extract, demonstrating sustained antihypertensive drug release potential. F4 emerged as the optimum formulation with excellent mucoadhesive strength, mechanical integrity, and sustained in vitro/ex vivo release over 8 hours. These findings underscore Grewia asiatica’s promise in buccal delivery. Further in vivo validation is recommended to confirm therapeutic outcomes and patient acceptability.
Acknowledgments
The authors acknowledge ACME Research Solutions for providing necessary facilities and the local suppliers for authenticated Grewia asiatica raw materials.
Conflict of Interest
No conflict of interest is declared by the authors.
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