INTRODUCTION:

Hypertension, defined as sustained elevation of systemic arterial blood pressure (≥140/90mmHg), represents one of the most prevalent chronic diseases worldwide and a leading modifiable risk factor for cardiovascular morbidity and mortality. According to the World Health Organization, an estimated 1.4 billion adults aged 30-79 years had hypertension in 2024, representing 33% of the population in this age range. The prevalence has increased dramatically from 650 million in 1990, with the burden disproportionately affecting low- and middle-income countries where two-thirds of hypertensive individuals reside¹.

In the United States, recent data from the National Health and Nutrition Examination Survey (August 2021-August 2023) revealed that 47.7% of adults have hypertension, with higher prevalence in men (50.8%) compared to women (44.6%), and a progressive increase with age reaching 71.6% in individuals aged 60 years and older². Alarmingly, approximately 44% of adults with hypertension worldwide remain unaware of their condition, contributing to inadequate disease management and increased cardiovascular complications.

Hypertension is directly associated with increased risk of coronary artery disease, heart failure, stroke, chronic kidney disease, and premature death. The condition imposes substantial economic burden on healthcare systems globally due to direct medical costs and indirect costs related to disability and premature mortality. Effective blood pressure control requires long-term pharmacological therapy combined with lifestyle modifications, presenting significant challenges in terms of medication adherence and therapeutic compliance.

Atenolol (4-(2-hydroxy-3-isopropyl amino propoxy) phenyl acetamide) is a second-generation cardio-selective β1-adrenergic receptor antagonist approved by the U.S. Food and Drug Administration for management of hypertension, angina pectoris, and acute myocardial infarction. The drug exhibits preferential blockade of β1-adrenoceptors located predominantly in cardiac tissue, thereby reducing heart rate, myocardial contractility, and cardiac output while minimizing β2-mediated broncho-constrictive effects³.

The oral mucosa represents an attractive alternative route for systemic drug delivery, offering several physiological and pharmacokinetic advantages over conventional oral administration. Mucoadhesion refers to the state in which a material (natural or synthetic polymer) adheres to mucous membrane for extended periods, serving as an effective strategy to prolong drug residence time at absorption sites. Mucoadhesive drug delivery systems have gained considerable attention in pharmaceutical research due to their ability to maintain intimate contact between dosage form and mucosal surface, thereby enhancing drug absorption and therapeutic efficacy^4-8.

MATERIALS AND METHODS:

Materials:

Active Pharmaceutical Ingredient, Atenolol (99.5% purity) was obtained as gift sample from pharmaceutical manufacturer. Polymers, and other chemical reagents were all procured from authorised dealers. All chemicals and reagents used were of analytical grade. Distilled water was used throughout the experimental work.

Formulation Development:

Preformulation Studies:

Drug-Excipient Compatibility Studies:

Compatibility between atenolol and selected polymers was evaluated using FTIR spectroscopy and DSC thermal analysis. Physical mixtures of drug and excipients (1:1 ratio) were prepared by trituration and stored at 40°C/75% RH for 4 weeks in sealed glass vials. Samples were analyzed at 0, 2, and 4 weeks to detect any physicochemical interactions⁹.

Solubility Studies:

Solubility of atenolol was determined in distilled water, phosphate buffer pH 6.8, and phosphate buffer pH 7.4 using shake-flask method. Excess drug was added to 10 mL of respective media in stoppered conical flasks and agitated at 37±0.5°C for 24hours. Solutions were filtered through 0.45μm membrane filters and analyzed spectrophotometrically at λmax 274nm.

Preparation of Atenolol Buccal Patches:

Buccal patches were prepared by solvent casting technique¹⁰. The formulation composition is presented in Table 1.

Table 1: Formulation composition of atenolol buccal patches

Ingredients (mg)	F1	F2	F3	F4	F5	F6	F7	F8
Atenolol	50	50	50	50	50	50	50	50
HPMC K4M	250	200	150		200	150	100
Sodium alginate				250	50	100	150	200
Carbopol 934P	50	100	150	50	50	50	50	100
PVP K-30	50	50	50	50	50	50	50	50
Propylene glycol (30\% w/w)	105	105	105	105	105	105	105	105
Distilled water	q.s.	q.s.	q.s.	q.s.	q.s.	q.s.	q.s.	q.s.

Formulation Procedure:

Accurately weighed HPMC K4M, sodium alginate, and carbopol 934P were dispersed separately in distilled water with continuous stirring until complete hydration and formation of clear viscous solutions. Atenolol was dissolved in minimal quantity of distilled water with constant stirring. PVP K-30 was dissolved in small volume of distilled water separately. All polymer solutions were mixed together followed by addition of atenolol solution with continuous stirring for 30minutes to ensure uniform dispersion. Propylene glycol (30\% w/w of total polymer weight) was added as plasticizer and mixed thoroughly. The homogenous polymeric dispersion was allowed to stand for 30 minutes to remove entrapped air bubbles. The resulting solution was poured onto circular glass petri dishes (10cm diameter) pre-coated with glycerin and dried in hot air oven at 45°C for 24hours. After complete drying, patches were carefully peeled off and cut into circular patches of 2.5 cm diameter (area = 4.91cm²). Backing membrane was prepared by casting 5\% w/v ethyl cellulose solution in dichloromethane onto backing layer of patches and dried. Patches were stored in desiccator containing fused calcium chloride until further evaluation.

Characterization of Buccal Patches:

Physical Appearance:

All formulated patches were visually inspected for color, clarity, flexibility, and smoothness. Any evidence of air bubbles, cracks, or imperfections was noted.

Weight Variation:

Ten patches from each formulation batch were randomly selected and weighed individually using electronic analytical balance (Shimadzu AUX 220). Average weight and standard deviation were calculated.

Thickness Uniformity:

Thickness of patches was measured using digital micrometer screw gauge (Mitutoyo) at five different locations (four corners and center). Mean thickness and standard deviation were calculated from ten patches of each formulation.

Folding Endurance:

Folding endurance was determined by repeatedly folding the patch at the same place until it broke or folded up to 300 times without breaking, whichever occurred earlier. This test provides information about brittleness and flexibility of patches.

Tensile Strength:

Tensile strength was measured using Universal Testing Machine (Instron). Patches were cut into dumbbell shape (length 60mm, width 10mm) and placed between two clamps. Lower clamp was fixed while upper clamp was movable. Force was gradually applied until the patch broke. Tensile strength was calculated as:

Force at Break (g)

Tensile strength = -------------------------------------------

(g/cm²) Initial cross Sectional Area of sample (cm²)

Surface pH:

Surface pH was determined to investigate potential side effects in vivo, as acidic or alkaline pH may cause irritation to buccal mucosa. Patches were allowed to swell by keeping them in contact with 1mL of distilled water (pH 6.5±0.05) for 2hours at room temperature. pH was measured by bringing combined glass electrode near the surface of patch and allowing it to equilibrate for 1 minute. Measurements were performed in triplicate.

Moisture Content:

Patches were weighed individually and kept in desiccator containing fused anhydrous calcium chloride at room temperature for 24hours. Individual patches were weighed repeatedly until constant weight was obtained. Moisture content was calculated as percentage weight loss using formula:

Initial weight – Final weight

%Moisture = ------------------------------------ x100

Content Initial Weight

Moisture Absorption Capacity:

Patches were weighed accurately and placed in desiccator containing saturated solution of aluminum chloride maintaining 79.5% RH at room temperature. After 24hours, patches were removed and reweighed. Moisture absorption was calculated as:

Final weight – Initial weight

Moisture = ------------------------------------ x100

Absorption Initial Weight

Drug Content Uniformity:

Patches of known area (4.91 cm²) were cut and placed in 100mL volumetric flask containing phosphate buffer pH 6.8. Flasks were shaken for 24hours to extract drug completely. Solution was filtered through 0.45μm membrane filter and analyzed spectrophotometrically at 274 nm after appropriate dilution. Drug content was calculated using calibration curve. Six determinations were performed.

Swelling Index:

Pre-weighed patches were placed in petri dishes containing 10mL of phosphate buffer pH 6.8. At predetermined time intervals (0.5, 1, 2, 3, 4, 6, 8hours), patches were removed, excess surface water blotted with filter paper, and reweighed. Swelling index was calculated as:

(W2- W1)

SI = ------------------------ x 100

Where W1 is the initial dry weight of the patch and W2 is the weight of the swollen patch at a specific time interval.

Mucoadhesive Strength:

Ex vivo mucoadhesive strength was measured using modified physical balance method. Fresh goat buccal mucosa was obtained from local slaughterhouse, washed with phosphate buffer pH 6.8, and tied to glass vial filled with buffer solution. Patch was adhered to mucosa by applying light force for 2minutes. The assembly was hanged to the left arm of balance. Weight was gradually added to right pan until patch detached from mucosa. Mucoadhesive force was calculated as:

Ww .g

F = --------------

Where:

F = Mucoadhesive force or Bond strength (typically in N/m², N/cm², or Pa).

Ww= Weight of water/mass added to the pan at the point of detachment (in grams or kg).

g = Acceleration due to gravity (usually 980cm/s² or 9.8 m/s²).

A = Surface area of the buccal patch (in cm² or m²).

In Vitro Drug Release Studies:

In vitro drug release studies were conducted using Franz diffusion cell with effective diffusion area of 4.91 cm² and receptor volume of 50mL. Cellophane membrane (previously soaked in phosphate buffer pH 6.8 for 24 hours) was mounted between donor and receptor compartments. Receptor compartment was filled with phosphate buffer pH 6.8 maintained at 37±0.5°C with constant stirring at 100rpm using magnetic stirrer¹¹. Patch was placed on membrane with drug-loaded side facing receptor compartment. At predetermined time intervals (0.5, 1, 2, 3, 4, 5, 6, 7, 8hours), 5mL aliquots were withdrawn and replaced immediately with equal volume of fresh buffer to maintain sink conditions. Samples were filtered through 0.45μm membrane filter and analyzed spectrophotometrically at 274nm. Cumulative percentage drug release was calculated and plotted against time.

Drug Release Kinetics:

To determine mechanism of drug release, data obtained from in vitro release studies were fitted to various mathematical models namely, Zero-order kinetics, First-order kinetics, Higuchi model, Korsmeyer-Peppas model. The value of n in Korsmeyer-Peppas equation indicates release mechanism: n≤0.45 (Fickian diffusion), 0.45<n<0.89 (non-Fickian or anomalous transport), n≥ 0.89 (Case II transport). The model with highest correlation coefficient (r²) was considered as best fit model.

Stability Studies:

Optimized formulation was subjected to stability studies as per ICH guidelines. Patches were packed in aluminum foil and stored at different conditions: 25°C±2°C/ 60%±5% RH, 30°C±2°C/ 65%±5% RH, and 40°C±2°C/ 75%±5% RH. Samples were withdrawn at 0, 1, 2, 3, and 6months and evaluated for physical appearance, drug content, and in vitro drug release.

RESULTS AND DISCUSSION:

Drug-Excipient Compatibility Studies: FTIR Spectroscopy:

FTIR analysis was performed to detect possible interactions between atenolol and polymers. The pure drug exhibited characteristic peaks at:

· 3346 cm⁻¹ (N-H stretching of secondary amine)

· 3288 cm⁻¹ (O-H stretching of hydroxyl group)

· 2966 cm⁻¹ (C-H stretching of aliphatic groups)

· 1640 cm⁻¹ (C=O stretching of amide)

· 1512 cm⁻¹ (N-H bending)

· 1246 cm⁻¹ (C-O-C stretching of ether linkage)

HPMC K4M showed peaks at 3420 cm⁻¹ (O-H stretching), 2935 cm⁻¹ (C-H stretching), and 1056 cm⁻¹ (C-O stretching). Sodium alginate exhibited peaks at 3440 cm⁻¹ (O-H stretching), 1620 cm⁻¹ (asymmetric COO⁻ stretching), and 1420 cm⁻¹ (symmetric COO⁻ stretching). Carbopol 934P displayed peaks at 3010 cm⁻¹ (O-H stretching) and 1710 cm⁻¹ (C=O stretching of carboxylic acid). Physical mixture and optimized formulation showed all characteristic peaks of atenolol without significant shifting or disappearance, indicating absence of chemical incompatibility between drug and polymers.

Differential Scanning Calorimetry:

DSC thermogram of pure atenolol showed sharp endothermic peak at 153.2°C corresponding to its melting point, indicating crystalline nature of drug. HPMC K4M exhibited broad endothermic peak at 78°C due to loss of water molecules. Sodium alginate showed endotherm at 240°C corresponding to decomposition. Carbopol 934P exhibited broad endotherm around 100°C. Physical mixture demonstrated atenolol endothermic peak at 152.8°C with slight reduction in peak intensity but without significant shift in melting point. The optimized formulation showed similar pattern, confirming absence of drug-polymer interaction and maintenance of drug crystallinity in formulation.

Solubility Studies:

Solubility of atenolol was determined in different media. The results have been tabulated in table 2 under.

Table 2: Solubility of atenolol in different media (n=3, mean ± SD)

Medium	Solubility (mg/mL)
Distilled water	26.5 ± 1.2
Phosphate buffer pH 6.8	33.8 ± 1.5
Phosphate buffer pH 7.4	38.2 ± 1.8

Results indicated that atenolol exhibits pH-dependent solubility with increased solubility at slightly alkaline pH, which is advantageous for buccal delivery as salivary pH ranges from 6.5 to 7.5.

Drug Content Uniformity:

All formulations exhibited drug content within acceptable limits (96.85-99.28% of labeled claim), indicating uniform drug distribution and good manufacturing reproducibility (table 4). Slight variation is attributed to polymer viscosity differences affecting drug dispersion during casting.

Swelling Index:

Table 5: Swelling index of buccal patches at different time intervals (n=3, mean ± SD)

Formu-lation	2 hrs (%)	4 hrs (%)	6 hrs (%)	8 hrs (%)
F1	45.2 ± 2.8	68.5 ± 3.2	82.4 ± 3.8	95.8 ± 4.2
F2	62.8 ± 3.5	98.5 ± 4.8	128.6 ± 5.5	156.2 ± 6.2
F3	78.5 ± 4.2	125.8 ± 5.8	168.5 ± 7.2	198.5 ± 8.5
F4	58.5 ± 3.2	88.2 ± 4.2	115.8 ± 5.2	138.6 ± 6.5
F5	48.5 ± 2.9	72.8 ± 3.5	92.5 ± 4.2	108.5 ± 4.8
F6	55.2 ± 3.1	82.5 ± 3.8	108.2 ± 4.8	128.5 ± 5.5
F7	62.5 ± 3.4	95.8 ± 4.5	122.5 ± 5.5	145.8 ± 6.2
F8	68.8 ± 3.8	105.2 ± 4.8	138.5 ± 6.2	165.2 ± 7.2

Swelling index increased with time for all formulations, reaching maximum at 8 hours. Carbopol-containing formulations exhibited higher swelling due to ionization of carboxylic groups and electrostatic repulsion between polymer chains. Optimal swelling is essential for mucoadhesion as it facilitates intimate contact and chain interpenetration with mucus glycoproteins. Excessive swelling (F3, F8) may cause patient discomfort and premature detachment (table 5).

Mucoadhesive Strength and Residence Time

Table 6: Mucoadhesive strength and residence time of buccal patches (n=3, mean ± SD)

Formulation	Mucoadhesive Strength (N)	Residence Time (hrs)
F1	0.58 ± 0.05	6.2 ± 0.5
F2	0.82 ± 0.06	7.8 ± 0.6
F3	1.05 ± 0.08	8.5 ± 0.7
F4	0.68 ± 0.06	6.8 ± 0.5
F5	0.75 ± 0.05	7.5 ± 0.6
F6	0.88 ± 0.07	8.2 ± 0.6
F7	0.95 ± 0.07	8.6 ± 0.7
F8	0.78 ± 0.06	7.2 ± 0.6

Mucoadhesive strength ranged from 0.58 to 1.05 N, with carbopol-containing formulations exhibiting superior adhesion due to numerous carboxylic groups forming hydrogen bonds with mucin glycoproteins. Formulation F3 (highest carbopol content) demonstrated maximum mucoadhesive strength and residence time (8.5 hours), sufficient for once-daily or twice-daily administration. However, excessive adhesion may cause discomfort; thus, F5-F7 represent optimal balance between adhesion and patient comfort. HPMC and sodium alginate contributed to mucoadhesion through hydroxyl and carboxylate groups, respectively.

In Vitro Drug Release Studies:

In vitro drug release profiles of all formulations are presented in Figure 1 and Table 7.

At pH 6.8, alginate carboxylate groups ionize, causing polymer relaxation and faster drug diffusion.

Hence based on the above interpretation, the optimized Formulation is F5 (HPMC 200 mg + sodium alginate 50 mg + carbopol 50 mg) demonstrated optimal release profile with 65.8% release at 8 hours and 92.5% at 12 hours, suitable for once-daily administration.

Drug Release Kinetics:

Release data were fitted to various mathematical models to elucidate release mechanism.

All formulations best fitted Higuchi model (highest r² values: 0.9885-0.9918), indicating diffusion-controlled drug release from matrix system. Higuchi model describes drug release from insoluble matrix as square root of time-dependent process. Korsmeyer-Peppas model provided n values between 0.518-0.548 (0.45<n< 0.89), confirming non-Fickian (anomalous) transport mechanism involving combination of drug diffusion through swollen polymer matrix and polymer relaxation/erosion. This dual mechanism ensures sustained and controlled drug release suitable for prolonged therapeutic effect.

Stability Studies:

Optimized formulation F5 was subjected to stability studies for 6 months under different storage conditions.

Table 9: Stability data of optimized formulation F5 (n=3, mean± SD)

Storage Condition	Initial	3 Months	6 Months
Drug Content % Release at start
25°C±2°C; 60%±5% RH	99.28±1.65	98.85 ± 1.82	98.42±1.95
30°C±2°C; 65%±5% RH	99.28±1.65	98.52 ± 1.88	97.85±2.08
40°C±2°C; 75%±5% RH	99.28±1.65	97.85 ± 2.12	96.58±2.35
8-hour Drug Release (%)
25°C±2°C; 60%±5 RH	65.8±3.0	65.2 ± 3.2	64.5±3.5
30°C±2°C; 65%±5 RH	65.8 ± 3.0	64.8 ± 3.5	63.8±3.8
40°C±2°C; 75%±5 RH	65.8 ± 3.0	63.5 ± 3.8	62.2±4.2

No significant changes in physical appearance (color, flexibility, smoothness) were observed throughout storage period. Drug content remained above 96% even under accelerated conditions (40°C/75% RH), indicating good chemical stability. Minor reduction in drug release rate under accelerated conditions may be attributed to increased polymer cross-linking. Overall, formulation demonstrated satisfactory stability profile suitable for long-term storage.

DISCUSSION:

The present investigation successfully developed mucoadhesive buccal patches of atenolol using combination of hydrophilic polymers (HPMC K4M, sodium alginate, carbopol 934P) to address pharmacokinetic limitations of conventional oral therapy. The rationale for selecting these polymers was based on their well-established mucoadhesive properties, biocompatibility, and ability to provide controlled drug release. HPMC K4M was selected as primary matrix-forming polymer due to excellent film-forming properties, good swelling characteristics, pH-independent release behavior, and biocompatibility. HPMC forms hydrophilic gel layer upon contact with aqueous media, controlling drug diffusion through tortuous pathways created by swollen polymer chains. Carbopol 934P, a cross-linked polyacrylic acid derivative, was incorporated to enhance mucoadhesive strength through abundant carboxylic groups capable of forming hydrogen bonds and electrostatic interactions with sialic acid residues of mucin glycoproteins. Additionally, carbopol provides pH-sensitive swelling and prolonged drug release. Sodium alginate, a natural polysaccharide derived from brown seaweed, was included for its excellent mucoadhesive properties, biodegradability, and ability to form reversible gels. Alginate's carboxylate groups contribute to mucoadhesion while providing controlled erosion-based release. PVP K-30 served as binding agent improving polymer dispersion and film integrity. Propylene glycol (30% w/w) was employed as plasticizer to impart flexibility, reduce brittleness, and facilitate folding endurance by increasing free volume between polymer chains.

Comprehensive physicochemical characterization confirmed that formulated patches possessed desirable attributes for buccal drug delivery. Adequate tensile strength (2.15-2.92 MPa) and excellent folding endurance (>240 folds) ensure patches can withstand mechanical stress during handling, packaging, and application without breaking or cracking. These properties are crucial for patient acceptability and ease of administration. Mucoadhesive strength (0.58-1.05 N) and residence time (6.2-8.6 hours) were sufficient for prolonged drug absorption. Carbopol-containing formulations exhibited superior mucoadhesion due to extensive hydrogen bonding and chain interpenetration with mucus layer. Residence time exceeding 6 hours is adequate for once-daily or twice-daily dosing, significantly improving patient compliance compared to conventional multiple daily dosing. Controlled swelling (45-198% at 8 hours) is critical for mucoadhesion as it facilitates intimate contact with mucosal surface and creates hydrophilic gel layer for sustained release. Optimal swelling balances mucoadhesion and drug release without causing excessive bulkiness or patient discomfort. Surface pH (6.18-6.58) within physiological salivary range minimizes risk of mucosal irritation, burning sensation, or tissue damage, ensuring patient comfort during application.

Drug release kinetics analysis revealed Higuchi model as best fit (r² > 0.98), confirming diffusion-controlled release from matrix system. Korsmeyer-Peppas n values (0.518-0.548) indicated non-Fickian (anomalous) transport combining diffusion and polymer relaxation/erosion. This dual mechanism ensures zero-order-like release profile suitable for maintaining therapeutic plasma concentrations throughout dosing interval.

Buccal Patches of Atenolol offer Several Therapeutic Advantages:

Enhanced Bioavailability: Bypassing first-pass hepatic metabolism and gastrointestinal degradation potentially increases bioavailability from 50% (oral) to significantly higher values through transmucosal absorption.

Sustained Drug Release: Controlled release over 8-12 hours eliminates need for frequent dosing, reducing from 2-3 times daily to once or twice daily administration.

Reduced Dosing Frequency: Improved patient compliance particularly beneficial in chronic hypertension requiring lifelong therapy. Medication adherence is major challenge in hypertension management; simplified dosing regimen significantly improves compliance.

Rapid Onset of Action: Rich buccal blood supply facilitates rapid drug absorption and onset of therapeutic effect, advantageous in acute hypertensive episodes.

Avoidance of Gastrointestinal Side Effects: Direct systemic absorption bypasses gastric irritation and intestinal disturbances associated with oral administration.

Easy Self-Administration and Removal: Non-invasive application without need for healthcare professional intervention. Patch can be easily removed if adverse effects occur, providing safety advantage.

Stable Plasma Concentrations: Sustained release minimizes peak-trough fluctuations in plasma drug levels, reducing risk of dose-dependent adverse effects (hypotension, bradycardia) while maintaining therapeutic efficacy.

CLINICAL IMPLICATIONS:

Atenolol buccal patches represent promising therapeutic option for hypertension management, particularly beneficial for:

· Patients with poor oral medication compliance

· Elderly patients experiencing difficulty swallowing tablets

· Patients with gastrointestinal disorders affecting oral absorption

· Situations requiring rapid blood pressure control with sustained effect

· Patients experiencing gastrointestinal side effects with oral therapy

Clinical efficacy and safety must be established through well-designed pharmacokinetic and pharmacodynamic studies in human subjects. Comparative bioavailability studies versus conventional oral tablets are essential to quantify bioavailability enhancement. Long-term clinical trials should evaluate antihypertensive efficacy, safety profile, and patient acceptability.

FUTURE RESEARCH DIRECTIONS:

Incorporation of permeation enhancers (sodium glycocholate, bile salts) to improve transmucosal absorption. Unidirectional release design with impermeable backing layer directing drug release toward mucosa. Development of bi-layer patches with immediate-release and sustained-release layers for rapid onset and prolonged duration. Incorporation of taste-masking agents and flavoring agents to improve patient acceptability. Investigation of novel mucoadhesive polymers (thiolated polymers, nanoparticle-based systems). In vivo pharmacokinetic studies in animal models followed by human clinical trials. Long-term stability studies under tropical climate conditions. Patient preference and quality-of-life studies comparing buccal patches with conventional therapy.

CONCLUSION:

This comprehensive research investigation successfully formulated and characterized mucoadhesive buccal patches of atenolol for effective management of hypertension. Solvent casting technique using combinations of HPMC K4M, sodium alginate, carbopol 934P, and PVP K-30 yielded patches with excellent physicochemical properties, adequate mechanical strength, good mucoadhesive performance, and sustained drug release characteristics.

FTIR and DSC studies confirmed absence of drug-polymer interactions, ensuring chemical stability of atenolol in formulation. All formulations exhibited acceptable weight variation, thickness uniformity, folding endurance, tensile strength, and drug content uniformity. Surface pH remained within physiological range (6.18-6.58), minimizing risk of mucosal irritation. Mucoadhesive strength (0.58-1.05 N) and residence time (6.2-8.6 hours) were adequate for prolonged buccal retention. In vitro drug release studies demonstrated sustained release profile extending up to 12 hours. Release kinetics followed Higuchi model with non-Fickian transport mechanism involving diffusion and polymer relaxation. Optimized formulation F5 (HPMC 200 mg + sodium alginate 50 mg + carbopol 50 mg) exhibited optimal balance of mucoadhesion, mechanical properties, and drug release (65.8\% at 8 hours, 92.5\% at 12 hours). Stability studies demonstrated satisfactory physical and chemical stability for 6 months under various storage conditions.

Atenolol buccal patches represent innovative drug delivery system offering potential to overcome limitations of conventional oral therapy including poor bioavailability (50%), first-pass metabolism, and short half-life (6-7 hours) necessitating frequent dosing. By providing sustained drug release over extended duration with enhanced bioavailability through transmucosal absorption bypassing hepatic first-pass effect, buccal patches can significantly improve therapeutic efficacy, reduce dosing frequency, minimize adverse effects, and enhance patient compliance in chronic hypertension management.

The developed mucoadhesive buccal patch formulation demonstrates significant promise as alternative therapeutic approach for hypertension management. However, translation from laboratory bench to clinical practice requires extensive in vivo pharmacokinetic studies, clinical efficacy trials, safety evaluations, and regulatory approvals. With further optimization and clinical validation, atenolol buccal patches could become valuable addition to armamentarium of antihypertensive therapies, particularly benefiting patient populations requiring simplified dosing regimens and enhanced medication adherence.

This research contributes to growing body of evidence supporting buccal drug delivery as viable strategy for improving therapeutic outcomes in cardiovascular diseases. The methodologies, formulation strategies, and characterization techniques described herein provide foundation for development of mucoadhesive patches for other cardiovascular drugs suffering from similar pharmacokinetic limitations.

CONFLICT OF INTEREST:

The authors declare no conflict of interest.

REFERENCES:

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Received on 27.02.2026 Revised on 19.03.2026

Accepted on 04.04.2026 Published on 21.04.2026

Available online from April 24, 2026

Res. J. Pharma. Dosage Forms and Tech.2026; 18(2):128-136.

DOI: 10.52711/0975-4377.2026.00020

This work is licensed under a Creative Commons Attribution-Non Commercial-Share Alike 4.0 International License. Creative Commons License.

Formulation	Average Weight (mg)	Thickness (mm)	Folding Endurance	Tensile Strength (MPa)	Surface pH
F1	185.2± 3.8	0.38 ± 0.02	285 ± 8	2.85 ± 0.12	6.45 ± 0.08
F2	178.5± 4.2	0.35 ± 0.02	278 ± 6	2.68 ± 0.15	6.28 ± 0.12
F3	172.8± 3.5	0.32 ± 0.01	265 ± 7	2.42 ± 0.18	6.18 ± 0.10
F4	188.6± 4.5	0.40 ± 0.02	242 ± 9	2.15 ± 0.14	6.52 ± 0.09
F5	180.2± 3.9	0.36 ± 0.02	296 ± 5	2.92 ± 0.11	6.58 ± 0.07
F6	176.8± 3.2	0.34 ± 0.02	288 ± 7	2.78 ± 0.13	6.48 ± 0.11
F7	174.5± 4.1	0.33 ± 0.01	280 ± 6	2.55 ± 0.16	6.42 ± 0.09
F8	183.4± 3.7	0.37 ± 0.02	255 ± 8	2.28 ± 0.15	6.55 ± 0.08

Formulation	Moisture Content (%)	Moisture Absorption (%)	Drug Content (%)
F1	4.85 ± 0.28	12.45 ± 0.65	98.45 ± 1.85
F2	5.12 ± 0.32	18.28 ± 0.82	97.82 ± 2.12
F3	5.45 ± 0.38	22.85 ± 0.95	96.85 ± 2.35
F4	6.28 ± 0.42	15.62 ± 0.72	98.12 ± 1.95
F5	4.92 ± 0.26	13.85 ± 0.68	99.28 ± 1.65
F6	5.18 ± 0.30	15.42 ± 0.75	98.65 ± 1.78
F7	5.65 ± 0.35	17.68 ± 0.88	97.48 ± 2.08
F8	6.05 ± 0.40	16.92 ± 0.78	97.92 ± 1.88

	2 hrs	4 hrs	6 hrs	8 hrs	10 hrs	12 hrs
F1	18.5 ± 1.5	35.8 ± 2.2	52.5 ± 2.8	68.5 ± 3.2	82.5 ± 3.5	92.8 ± 3.8
F2	15.2 ± 1.2	28.5 ± 1.8	42.8 ± 2.5	58.5 ± 2.8	72.8 ± 3.2	85.5 ± 3.5
F3	12.5 ± 1.0	22.8 ± 1.5	35.5 ± 2.2	48.5 ± 2.5	62.8 ± 2.8	76.8 ± 3.2
F4	22.5 ± 1.8	42.5 ± 2.5	58.5 ± 3.0	72.5 ± 3.5	85.2 ± 3.8	95.5 ± 4.2
F5	16.8 ± 1.3	32.5 ± 2.0	48.8 ± 2.6	65.8 ± 3.0	80.5 ± 3.5	92.5 ± 3.8
F6	14.5 ± 1.1	28.8 ± 1.8	44.5 ± 2.5	60.5 ± 2.8	75.8 ± 3.2	88.5 ± 3.6
F7	13.2 ± 1.0	25.5 ± 1.6	39.8 ± 2.3	54.8 ± 2.7	69.5 ± 3.0	82.8 ± 3.5
F8	20.5 ± 1.6	38.5 ± 2.3	54.5 ± 2.8	68.8 ± 3.2	82.5 ± 3.6	93.5 ± 4.0

Formulation	Zero Order r²	First Order r²	Higuchi r²	Korsmeyer-Peppas r²	Best Fit Model
F1	0.9456	0.9682	0.9885	0.9912	0.548
F2	0.9512	0.9725	0.9902	0.9925	0.532
F3	0.9568	0.9758	0.9918	0.9935	0.518
F4	0.9368	0.9458	0.9618	0.9835	0.528
F5	0.9485	0.9705	0.9892	0.9918	0.542
F6	0.9528	0.9738	0.9908	0.9928	0.528
F7	0.9545	0.9745	0.9915	0.9932	0.522
F8	0.9428	0.9238	0.9708	0.9528	0.515

MATERIALS AND METHODS:

Materials:

Formulation Development:

Preformulation Studies:

Drug-Excipient Compatibility Studies:

Solubility Studies:

Preparation of Atenolol Buccal Patches:

Formulation Procedure:

Characterization of Buccal Patches:

Physical Appearance:

Weight Variation:

Thickness Uniformity:

Folding Endurance:

Tensile Strength:

Surface pH:

Moisture Content:

Moisture Absorption Capacity:

Drug Content Uniformity:

Swelling Index:

Mucoadhesive Strength:

In Vitro Drug Release Studies:

Drug Release Kinetics:

Stability Studies:

RESULTS AND DISCUSSION:

Drug-Excipient Compatibility Studies: FTIR Spectroscopy:

Differential Scanning Calorimetry:

Solubility Studies:

Physicochemical Characterization of Buccal Patches:

Physical Appearance:

Weight Variation:

Thickness Uniformity:

Folding Endurance:

Tensile Strength:

Surface pH:

Moisture Content and Moisture Absorption:

Drug Content Uniformity:

Swelling Index:

Mucoadhesive Strength and Residence Time

In Vitro Drug Release Studies:

Drug Release Kinetics:

Stability Studies:

DISCUSSION:

Buccal Patches of Atenolol offer Several Therapeutic Advantages:

CLINICAL IMPLICATIONS:

FUTURE RESEARCH DIRECTIONS:

CONCLUSION:

CONFLICT OF INTEREST:

REFERENCES: