To study the effect of Eudragit RL and RS in the formulation and Evaluation of Olmesartan Matrix Tablet

Mohd Bilal Sufi; Mohd Julebib Mohd Shafique*; Rajlaxmi Deolekar

Department of Pharmaceutics, New Montfort Institute of Pharmacy, Ashti, Dist – Wardha, (M.S)

*Correspondence: mjjulebib@gmail.com

DOI: https://doi.org/10.71431/IJRPAS.2026.5704      

INTRODUCTION

Hypertension is a chronic, multifactorial high blood pressure in the arteries and still one of the most important modifiable cardiovascular risk factors. Globally, about 1.3 billion adults are estimated to suffer from hypertension, however, it continues unrecognised and uncontrolled in a significant proportion of patients even with effective pharmacotherapy available [1-2]. This increasing demand is particularly pronounced in low and middle income countries, where rapid urbanization, lifestyle changes and limited health system resources have led to rising prevalence and poor control rates.[3-4] Hypertension is a well-established risk factor for various cardiovascular events like coronary artery disease, heart failure and peripheral vascular disease and cerebrovascular complications such as ischemic stroke as well as haemorrhagic stroke. [5-6] However, long-standing poorly controlled hypertension accelerates chronic kidney disease progression and end‑stage renal failure, contributing to escalating burden on health care resources and economic costs.[ 7-8] Hypertension is often asymptomatic and requires life-long treatment, thus optimizing long-term pharmacotherapy to improve adherence while ensuring stable blood pressure control represents a critical objective in contemporary cardiovascular care.[2,4]

Oral administration remains the most preferred route for chronic antihypertensive therapy because of its convenience, safety, and high level of patient acceptance.[9-10] One approach to rapid drug absorption is the conventional immediate‑release formulations, leading to high peak plasma concentrations followed by relatively short duration action resulting in unsatisfactory effect intervals requiring multiple daily dosing with plasma level variability (peaks and troughs) correlated with elegant treatment response. [9-11] For comparison, oral sustained or controlled-release dosage forms are used to keep drug concentrations in a therapeutic window for an extended period, thereby reducing dosing frequency, minimizing peak‑trough variability, and potentially lowering the incidence of dose‑related adverse effects.[9-10] Controlled‑release systems employ a variety of physicochemical mechanisms—such as diffusion through a polymeric matrix, erosion or dissolution of the matrix, or a combination of swelling‑controlled and diffusion‑controlled processes—to modulate drug release in a predictable manner. [9-10] Of these, matrix tablets have become especially important due to their relatively simple manufacturing, robustness, and suitability for a wide range of drugs with different physicochemical properties. [9, 12] Recent advances in polymer science and quality‑by‑design approaches have further enabled the development of matrix systems capable of providing tailored release profiles for once‑daily antihypertensive therapy.[10, 13]

Matrix tablets are a type of solid oral dosage form, where the active pharmaceutical ingredient is uniformly dispersed within a polymeric or lipid matrix that modulates drug release as gastrointestinal fluids permeate the system.[9-11] They can be broadly classified according to the nature of the matrix‑forming excipient into hydrophilic, hydrophobic, and lipid or wax matrices, as well as more complex multi‑polymeric systems [9,14]. Hydrophilic matrices, typically based on cellulose derivatives or other swellable polymers, form a viscous gel layer upon hydration through which drug molecules diffuse; hydrophobic matrices rely predominantly on pore formation and diffusion through a less swellable structure, while erosion of the matrix can contribute to release in all systems to varying extents. [9, 11] Matrix tablets have several advantages such as preparation by direct compression or wet granulationuniform drug release over prolonged periods, and the possibility of modulating kinetics by varying polymer type, viscosity grade, and concentration. [9-10] On the other hand, they also possess certain disadvantages as risk of dose dumping in abnormal states (e.g. under extreme pH level or agitation), release profiles being sensitive to GI motility and selection of polymer must be carefully considered to achieve desired rates of swelling, erosion, and diffusion processes. [11- 12] Accordingly rational design of matrix formulations needs a systematic understanding of the interplay between drug properties, polymer characteristics, and processing variables that jointly govern the in vitro and in vivo release behaviour. [9-10]

Olmesartan medoxomil along with its active form olmesartan which is an oral prodrug anti-hypertensive agent used in the treatment of mild to moderate essential hypertension. [15-16] Following oral administration, olmesartan medoxomil is rapidly hydrolysed via esterase-mediated mechanisms to yield the active acid form of the drug, olmesartan, which competitively inhibits angiotensin II binding at AT1 receptors located on vascular smooth muscle and other target tissues so that its antihypertensive action becomes effective. [15-17] Pharmacokinetic studies reveal olmesartan medoxomil has low aqueous solubility, approximate oral bioavailability of 20–30% and a terminal elimination half‑life of 10–15 hours, which is consistent with once‑daily clinically dosed regimens. [15, 18-19] The drug is moderately absorbed in the proximal small intestine, highly protein bound, and eliminated mostly unchanged in urine and bile with only a background level of metabolism that results in little potential for clinically significant drug–drug interactions [16, 18] Clinically, olmesartan medoxomil is indicated for the treatment of hypertension, either as monotherapy or in combination with other antihypertensive agents and has been shown to provide effective blood pressure reduction maintained over a 24-h period, with an acceptable tolerability profile. [16-17] However, its low solubility and incomplete bioavailability, along with requiring chronic treatment suggested the need for formulations that would increase dissolution and provide more prolonged plasma levels to enhance compliance.[ 20-21]

To address the biopharmaceutical restrictions of olmesartan medoxomil, various advanced delivery systems have been examined, including self‑nanoemulsifying drug delivery systems, nanoparticles, nanosuspensions, oleogels and transdermal and buccal platforms [20-22]. These approaches have generally succeeded in enhancing dissolution, permeability, and systemic exposure, often achieving several‑fold increases in bioavailability compared with conventional tablets. [20-22] However, numerous of these technologies are complex to manufacture, require specialized excipients or explore non‑oral routes that may limit their broad applicability, cost-effectiveness, or patient acceptance in routine hypertension management.[20, 24] In contrast, sustained‑release oral matrix tablets based on established excipient systems provide a simpler and more industry‑friendly approach to achieving prolonged drug release and smoother pharmacokinetic profiles for once‑daily therapy.[13, 25] Despite the widespread investigation of sustained‑release matrices for other antihypertensive agents such as losartan and valsartan, there remains comparatively limited work focusing on systematic matrix design for olmesartan medoxomil using robust rate‑controlling polymers.[25-27]

Among the various matrix‑forming and film‑forming excipients, Eudragit polymers, copolymers of methacrylic acid and methacrylate esters, occupy a key position in the design of controlled‑release oral dosage forms.[28-29] Eudragit polymers are commercially available in various grades that differ according to their charge characteristics, solubility and functional groups which allows a formulation scientist to control the drug release either by time or pH activated or permeability driven. This can be achieved using neutral, water-insoluble but swellable low quaternary ammonium content copolymers based on Eudragit RL or Eudragit RS, containing a low content of quaternary ammonium groups, which impart pH‑independent permeability to dissolved drug molecules.[28, 30] The principal structural distinction between RL and RS lies in the density of quaternary ammonium moieties: Eudragit RL possesses a higher fraction of these cationic groups and therefore exhibits greater permeability to water and dissolved solutes, whereas Eudragit RS contains fewer quaternary ammonium groups and forms a more diffusion‑resistant matrix. [28, 32-33] The presence and concentration of quaternary ammonium functionalities influence water uptake, swelling behaviour, ionic interactions, and the formation of aqueous channels within the hydrated polymer, thereby directly modulating the rates of diffusion, erosion, and overall drug release.[31, 33-34] Because these polymers are physiologically inert, exhibit good compressibility, and are compatible with a wide range of active ingredients, they are extensively used as rate‑controlling agents in matrix tablets, coated multiparticulate, and osmotic systems.[28, 30, 35]

Eudragit RL and RS have been successfully applied in the formulation of sustained‑release matrix systems and coatings for numerous drugs, including non‑steroidal anti‑inflammatory agents, beta‑blockers, and other cardiovascular medications.[36-38] Studies have demonstrated that by varying the RL:RS ratio, it is possible to fine‑tune the permeability of the matrix or coating and thereby modulate the lag time, release rate, and duration of drug delivery over 12–24 hours.[28, 30, 37] For example, matrix and multiparticulate systems designed with higher proportions of Eudragit RL generally exhibit faster water uptake and drug diffusion, whereas formulations enriched in Eudragit RS show more prolonged and diffusion‑limited release profiles.[28, 33, 39] In addition, the combination of Eudragit RL/RS with hydrophilic polymers or osmotic agents has been reported to provide complex release behaviours, such as sigmoidal or chronotherapeutic profiles, which underscore the versatility of these copolymers as rate‑controlling excipients.[34, 37, 40] Despite this extensive use, the influence of specific RL:RS ratios and total polymer loading on the release of poorly soluble, weakly acidic antihypertensives such as olmesartan medoxomil has not been comprehensively characterized in conventional matrix tablet designs.[28, 41]

While several formulation strategies have been proposed to enhance the solubility and bioavailability of olmesartan medoxomil, only a limited number of studies have systematically examined sustained‑release oral matrices based on methacrylate copolymers.[20-21, 42] Existing work on olmesartan tablets is largely focused on immediate‑release products or on advanced nanocarrier systems rather than on robust, scalable matrix technologies employing Eudragit RL and RS as primary release‑modifying agents.[41-43] Moreover, although the release‑modulating potential of RL/RS mixtures has been demonstrated for other drugs, there is a paucity of data regarding the optimization of RL:RS ratios specifically for olmesartan, particularly with respect to achieving near zero‑order kinetics and 24‑hour coverage using a single oral dose. [28, 30, 37] Critical formulation variables such as polymer level, drug‑to‑polymer ratio, matrix porosity, and the interplay between swelling and erosion have not been systematically explored in the context of olmesartan medoxomil, leaving a clear gap in knowledge regarding the rational design of such systems.[10, 13, 44] There is thus a need for focused research that correlates Eudragit RL and RS concentrations and ratios with in vitro release parameters and, by extension, with the desired pharmacokinetic behaviour for sustained antihypertensive therapy.[9, 28]

In this context, the present study aims to investigate the influence of Eudragit RL and Eudragit RS on the formulation and evaluation of sustained‑release matrix tablets of Olmesartan with the objective of achieving prolonged drug release, improved therapeutic efficacy, and enhanced patient compliance

MATERIALS AND METHODOLOGY

Materials

Olmesartan Medoxomil was purchased as gift sample from Swapnroop Drugs and Pharmaceuticals, Aurangabad, India. Hydroxypropyl methylcellulose (HPMC K15M), Eudragit RL, Eudragit RS, and methanol were procured from Research Lab Fine Chem Industries. Polyvinylpyrrolidone (PVP K30) was obtained from Simpson, while microcrystalline cellulose (Avicel PH-102), colloidal silicon dioxide, talc, and magnesium stearate were purchased from Thermosil Lab Fine Chem Industries. All excipients and reagents used in the formulation and evaluation of the sustained-release tablets were of analytical or pharmaceutical grade and were used without further purification.

Instruments

The study employed a Shimadzu UV-1800 UV–Visible spectrophotometer for spectrophotometric analysis and a Bruker FT-IR spectrophotometer equipped with an Attenuated Total Reflectance (ATR) accessory for drug–excipient compatibility studies. Tablets were compressed using a Remik Mini Press rotary tablet compression machine. In vitro dissolution studies were performed using an Electro Lab TDT-08L USP Type II (Paddle) dissolution apparatus. A Shimadzu TX4231 digital weighing balance (Mumbai) was used for accurate weighing of materials, while tablet hardness was measured using a Pfizer hardness tester and friability was determined using a PSM Industries friabilator (Bengaluru). All instruments were calibrated prior to use according to standard laboratory procedures.

METHODOLOGY

Preformulation Studies

Determination of Absorption Spectrum (λmax)

Olmesartan stock solution was prepared by dissolving accurately weighed drug in methanol to get the concentration of 100 µg/mL. An appropriate fraction of the stock solution was suitably diluted followed by scanning of the solution over the range of wavelengths 200–400 nm, using methanol as blank in the UV-Visible spectrophotometer. The wavelength (λmax) with the highest absorbance of the compound peak was noted and chosen for further quantitative estimation of the drug.[45]

Preparation of Calibration Curve

Standard stock solution of 100µg/mL of Olmesartan was prepared in methanol. Appropriate aliquots were removed from this stock solution and diluted with methanol to make up 5, 10, 15, 20 and 25 µg/mL. A UV–Visible spectrophotometer was used to measure the absorbance of each solution at 257 nm. A calibration curve was plotted to determine the linear of the method as expected in the analytical method, a regression equation and R² were calculated and plotted.[46]

FTIR Compatibility Study

The compatibility between Olmesartan and the selected excipients, including Eudragit RL and Eudragit RS, was evaluated using Fourier Transform Infrared (FTIR) spectroscopy. FTIR spectra of pure Olmesartan and physical mixture of drug and excipients (1:1 ratio) were obtained by ATR technique in the range of 4000–400 cm⁻¹. Characteristic functional group peaks of the pure drug were compared with its physical mixture for any significant shift in peaks, disappearance or emergence of new peaks.[47-48]

FORMULATION OF SUSTAINED RELEASE TABLET:

Olmesartan medoxomil sustained-release tablets were formulated by dry compression. Drug and all the excipients, HPMC K15 M, Eudragit RL, Eudragit RS, PVP K30, Microcrystalline cellulose, colloidal silicon dioxide, talc and Magnesium stearate were precisely weighed as per each batch (B1–B12) and then sifted through Sieve No. 22 to get a homogenous particle size. Sieved drug and excipients were well mixed to have homogenous distribution of the drug and matrix forming polymer. MCC acted as a diluent to maintain the weight of the tablets and to complement the compressibility and PVP K30 functioned as a tablet binding agent. Colloidal silicon dioxide was added to impart a good flow property, followed by talc to further enhance powder flow. Magnesium stearate was finally added, mixed gently and lubricated without affecting the integrity of the tablet. The formed lubricated blends were then compressed into tablets using a rotary tablet compression machine, which are sustained-release tablets with even weight, proper mechanical strength and steady drug release profile. The prepared tablets were evaluated for different physicochemical and in vitro properties test to get the optimized batch.[49]

Table 01. Formulation Table

Evaluation of Precompression Parameters

Bulk Density

A known amount of powder blend was taken out and transferred into a clean dry graduated measuring cylinder with great care, so that no compaction of the powder had taken place.[50] The bulk volume was noted, and bulk density was calculated as the ratio of powder weight to bulk volume (g/mL).

Tapped Density

The tapped density was carried out by putting the graduated cylinder filled with powder blend on the tapped density apparatus and tapping the cylinder till a constant volume was obtained.[51] The actual tapped volume was then measured and the tapped density was obtained by dividing weight of the powder by the tapped volume.

Hausner Ratio

The Hausner ratio was calculated using the values of bulk density and tapped density according to the equation:

The obtained values were used to evaluate the flow characteristics of the powder blends.

Carr's Compressibility Index

Carr's Compressibility Index was calculated using the measured bulk density and tapped density according to the following equation:

The calculated values were used to assess the compressibility and flowability of the powder mixtures before compression.[52]

Angle of Repose

The angle of repose was determined using the fixed funnel method. The powder blend was allowed to flow freely through a funnel positioned at a fixed height to form a conical heap.[53] The height and radius of the powder cone were measured, and the angle of repose was calculated using the equation:

where h is the height of the pile and r is the radius of the powder heap.

Evaluation of Post–compression Parameters

Weight Variation

Twenty tablets from each formulation were randomly selected and individually weighed using a calibrated digital analytical balance. The average tablet weight and percentage deviation from the mean weight were calculated and compared with pharmacopeial specifications to evaluate weight uniformity.[54]

Thickness

Thickness of ten tablets of each formulation was measured by using digital Vernier caliper. The average thickness was estimated and derived in millimetre to estimate the dimensional uniformity of prepared tablets.[55]

Hardness

The hardness of the tablets was determined by Monsanto hardness tester. Six tablets were randomly selected from each formulation and the force required to diametrically break each tablet was noted in kg/cm². The average was taken of this hardness value.

Friability

A Roche friabilator was used to assess the friability of the tablets. The 20 pre-weighed tablets were rotated for 4 minutes at 25 rpm for total of 100 revolutions.[56] The tablets were reweighed after dedusting to calculate the percentage friability using the standard formula. Friability values of less than 1% were deemed as acceptable.

Drug Content

An accurate weight of 10 tablets of each formulation was weighed and powdered. A quantity of powder equivalent to 20 mg of Olmesartan was transferred to volumetric flask and extracted thoroughly with methanol by sonication and filtered through Whatman filter paper and then diluted accordingly. The absorbance of the sample was measured at 257 nm using a UV–Visible spectrophotometer and the percentage drug content was determined from the calibration curve.[57]

In-vitro Drug Dissolution Study

The in-vitro dissolution study was conducted in USP Type II (Paddle) dissolution apparatus. This dissolution medium comprised 900 mL of phosphate buffer (pH 6.8), maintained at 37 ± 0.5°C and the paddle speed was varied. A single tablet of each formulation was introduced into the dissolution vessel; the samples (5 mL) were then collected at specific time points of 0.5, 1, 2, 4, 6, 8, 10 and 12 hours, with 5 mL of fresh dissolution medium added to replace what had already been collected and kept at the same temperature. The samples were filtered, diluted if required and spectrophotometrically analysed at 257 nm. The cumulative percentage drug release was determined and plotted against time.[58]

Accelerated Stability Study

The optimized formulation was then accelerated tested for its stability as per ICH guidelines. The tablets were packed in proper container the tablets were stored for 15 days at 75% RH, 40 ± 2°C. The tablets were tested at the end of storage period for physical appearance, weight variation, thickness, hardness, friability, drug content, and in-vitro dissolution profile to establish the stability of the formulation and effect of storage environment on the sustained release of the drug.[58]

RESULT AND DISCUSSION

PREFORMULATION STUDIES:

Determination of absorption Spectra – λ Max:

The UV absorption spectrum of Olmesartan in methanol (200–400 nm) showed a λmax at 257 nm. Therefore, 257 nm was selected for calibration, drug content estimation, dissolution, and stability studies due to its high sensitivity and reproducibility as depicted in Fig 01.

Fig 01. Absorption spectrum of Olmesartan

Calibration Curve:

The calibration curve of Olmesartan showed good linearity over the studied concentration range with a correlation coefficient (R² = 0.9938) as shown in Fig 02. The regression equation confirmed compliance with Beer–Lambert's law, validating the UV spectrophotometric method for quantitative estimation.

Fig 02. Calibration Curve

FTIR Compatibility Study of Olmesartan with Excipients

The compatibility of Olmesartan with the selected excipients, including Eudragit RL and Eudragit RS, was evaluated using Fourier Transform Infrared (FTIR) spectroscopy. The FTIR spectra of the pure drug and the physical mixture (1:1) were carefully compared (Fig 03 and Fig 04). The absorption peaks of the functional groups of Olmesartan did not change in the physical mixture in comparison to the original mixture without any significant shift, disappearance or appearance of additional peaks. These results were consistent with the absence of any chemical compatibility between the drug and excipients, an excellent result throughout the drug formulation process. The compatibility study also revealed that both Eudragit RL and Eudragit RS are appropriate polymers for use in the development of sustained release Olmesartan matrix tablets as a release controlling polymer.

Fig 03. FTIR of pure Olmesartan 

Fig 04. FTIR of Olmesartan with excipient mixture (Physical mixture 1:1)

PRECOMPRESSION PARAMETERS:

 Bulk Density:

The bulk density for the powder blends of the various formulations (B1-B12) was measured to determine the packing characteristics of the granules before compression. The bulk density values obtained from the different formulations ranged between 0.34 ± 0.01 and 0.46 ± 0.01 g/mL reflecting slight difference in the formulations that occurred due to the different concentrations of Eudragit RL and Eudragit RS polymers used in the preparation. Slightly lower bulk density was achieved for the formulations with relatively high concentrations of polymers due to the lightweight and porous nature of the polymers. The obtained values suggested satisfactory packing ability of the powder blends and indicated their suitability for direct compression.

Tapped Density:

The tapped density was obtained by tapping the cylinder till the volume becomes constant. Tapped density values were found to be in the range of 0.45 ± 0.01 – 0.57 ± 0.01 g/mL for all the formulations. The tapped density increased over the bulk density which was due to the loss in interparticle void space upon tapping. The narrow range of values was good packing efficiency of the powder blends and confirmed that the formulations had good compressibility characteristics needed for sustained-release tablet formulation.

Hausner Ratio:

Hausner ratio was used to measure the flowability of the powder blends. The values ranged between 1.23 ± 0.02 and 1.32 ± 0.03. The values of Hausner ratio of most formulations were less than 1.30, which is good to fair flow property appropriate for direct compression. Batch B8 showed the lowest Hausner ratio (1.23 ± 0.02), indicating superior flowability, whereas Batch B7 exhibited the highest value (1.32 ± 0.03), reflecting comparatively lower flow characteristics. However, none of the formulations had to be supplemented with any flow enhancing agent to give an acceptable flow behaviour.

Carr’s Compressibility Index:

Carr's Compressibility Index was determined to evaluate the compressibility and flow characteristics of the powder blends. The values ranged from 18.5 ± 0.6% to 24.4 ± 0.8%. Formulations exhibiting lower angle of repose values demonstrated better flowability due to reduced interparticle friction. Batch B8 showed the lowest angle of repose (28.5 ± 0.5°), indicating excellent flow characteristics, whereas Batch B7 exhibited the highest value (34.0 ± 0.8°), suggesting comparatively moderate flow. All formulations however, were within limits for direct compression, and thus had satisfactory packing and compression properties.

Angle of repose:

The angle of repose was determined to examine the frictional properties among powder particles and to evaluate the flow properties. The angle of repose values ranged from 28.5 ± 0.5° to 34.0 ± 0.8°. The products with lower angle of repose value showed the higher flowability of the product because the interparticle friction is less. Batch B8 had the best flow characteristic with the lowest angle of repose (28.5 ± 0.5°), while Batch B7 had the highest angle of repose (34.0 ± 0.8°), suggesting that the flow properties were comparatively poor. All powder blends showed good flowability, which is important for the uniform filling of the dies and consistency in tablet weight during compression.

Table 02. Precompression Parameters

POST COMPRESSION PARAMETERS:

Weight Variation and % deviation:

The weight variation test demonstrated excellent uniformity among all prepared sustained-release matrix tablets. All the tablets in each formulation had a mean weight of around 300 mg and the percentage weight variation was within the acceptable pharmacopoeial limit and was within the range of ±0.87% to ±1.12%. The minimal variation in tablet weight indicated uniform powder flow, consistent die filling, and reproducible compression throughout the manufacturing process. The results further confirmed that incorporation of varying concentrations of Eudragit RL and Eudragit RS did not adversely affect the weight uniformity of the formulations.

Thickness:

The thickness of the formulated tablets ranged from 4.05 to 4.18 mm, indicating excellent dimensional uniformity among all batches. Minimal thickness variations were noted resulting from polymer concentrations and compressibility. Thickness uniformity ensured even compression during tablet manufacturing and showed even distribution of the formulation ingredients. Such dimensional consistency is essential for maintaining tablet appearance, packaging quality, and reproducible drug release characteristics.

Hardness:

The hardness values of sustained release matrix tablets showed good mechanical strength with the hardness values ranging from 6.2 to 7.9 kg/cm². The hardness of the formulations containing a higher concentration of Eudragit polymers usually showed higher value due to better matrix formation and interparticle bonding properties. The samples of batch B8 had the highest hardness value (7.9 kg/cm²), while the batches of B4 had the lowest hardness value (6.2 kg/cm²). All formulations possessed sufficient mechanical integrity to withstand handling, transportation, packaging, and storage without significant breakage while maintaining their sustained-release characteristics.

Friability:

Friability testing demonstrated excellent mechanical resistance of all prepared formulations. The friability was between 0.48 and 0.64% which is lower than the official pharmacopoeial limit of 1.0%. Batch B3 exhibited the lowest friability (0.48%), whereas batch B7 showed the highest value (0.64%), although still within acceptable limits. The friability values were very low which showed that the tablets were strong enough to overcome abrasion and mechanical stress that occurs during their manufacture, packing, transport and normal handling.

Drug Content:

All formulations were found to be uniformly distributed after analysis of the drug content in the formulation. The range of percentage drug content was 98.6 % to 99.7 % that showed good content uniformity and efficient mixing of excipients with the drug. Batch B8 showed the highest drug content (99.7%), while Batch B7 exhibited the lowest value (98.6%). In all formulations, the pharmacopoeial specification was acceptable which validated the formulation process and resulted in uniformity of dose in the prepared sustained release tablets.

Table 03. Post compression Parameters

In-vitro studies of drug dissolution:

The in-vitro dissolution study demonstrated that the release profile of Olmesartan was significantly influenced by the concentration and ratio of Eudragit RL and Eudragit RS used as release-controlling polymers. Formulations with a higher proportion of Eudragit RL showed a comparatively more rapid release of drug because of its high permeability and more number of quaternary ammonium group in the matrix facilitates easier penetration of dissolution media in the matrix. In contrast, formulations containing a higher proportion of Eudragit RS showed slower and more controlled drug release owing to its comparatively lower permeability and denser polymer matrix. Batch B4, B8 and B10 showed efficient sustained-release profile with 98.6%, 98.2% and 97.9% cumulative drug release after 12 h, respectively, amongst all formulations while all of the other batches showed lesser profile. In contrast, Batch B12 showed the slowest release pattern, achieving only 71.9% drug release after 12 hours, indicating that excessive polymer retardation considerably reduced the diffusion of drug molecules from the matrix. The drugs were progressively released from the intermediate formulations with a range between 80% and 96% release corresponding to the choice of polymer ratio. The overall study of drug dissolution demonstrated that optimal design of both Eudragit RL and Eudragit RS formulations yielded extended drug release protecting the drug with appropriate optimisation, which can be used for sustained drug supply.

Table 04. Drug Dissolution Studies

Fig 05. In–vitro Drug Dissolution Studies

Determination of optimized batch:

Based on the comprehensive evaluation of post-compression characteristics and in-vitro drug release studies, Batch B8 was identified as the optimized formulation. The formulation exhibited excellent physical properties, including satisfactory hardness (7.9 kg/cm²), low friability (0.57%), acceptable thickness (4.09 mm), uniform tablet weight, and the highest drug content (99.7%). Furthermore, Batch B8 achieved a cumulative drug release of 98.2% over 12 hours, providing a desirable sustained-release profile without excessive initial burst release. The optimized balance of Eudragit RS effectively regulated drug diffusion from the polymeric matrix, ensuring prolonged therapeutic release while maintaining excellent tablet integrity. Therefore, Batch B8 was selected as the optimized sustained-release formulation for Olmesartan.

Accelerated stability study:

The optimized formulation (Batch B8) was subjected to accelerated stability studies under ICH-recommended storage conditions to evaluate its physical integrity and drug release performance. The physical characteristics of the tablets including appearances, mean weight, thickness, hardness, friability, drug content and dissolution profile did not differ significantly after 15 days storage. Excellent formulation stability was revealed with an average tablet weight of 300 ± 1.3 mg, thickness of 4.1 mm, friability of only 0.59% and drug content of 99.4%. The dissolution profile following stability testing was similar to that of the freshly prepared formulation indicating that there was essentially no change in dissolution properties following stability testing due to the release of Olmesartan. The results showed that the optimized formulation could be physically and chemically stable and maintain a sustained-release effect for a long time under accelerated storage conditions and this could be applied as a long-term pharmaceutical.

Table 05. Stability Study After 15 days

Fig. 06. stability studies for drug release

CONCLUSION:
The study successfully developed sustained-release matrix tablets of Olmesartan using Eudragit RL and Eudragit RS with HPMC K15M as release-modifying polymers. Preformulation studies confirmed drug purity and compatibility with the selected excipients. All formulations exhibited satisfactory pre- and post-compression characteristics within pharmacopoeial limits. In vitro dissolution studies showed that drug release was influenced by the type and concentration of polymers, with Eudragit RL enhancing release and Eudragit RS providing prolonged release. Among all batches, B8 was identified as the optimized formulation, showing 99.7% drug content and 98.2% drug release over 12 hours. Stability studies confirmed that B8 remained physically and chemically stable. Overall, the optimized formulation demonstrated effective sustained drug release, reduced dosing frequency, and potential for improved patient compliance in hypertension management.

REFERENCES:

1. Beheiry H, Auala T, Dawi E, Nur M, Ahmed M, Markos S, et al. P019 hypertension prevalence, health policy, and guidelines mapping: a comparative analytic study across nine african countries 2024. J Hypertens. 2024; 42(Suppl 3):e60.
2. De Bacquer D, Vanassche T, Brouwers S, Van De Borne P, Van Der Niepen P, De Backer T, et al. Prevalence, Awareness And Therapeutic Control Of Hypertension In Belgium: An Opportunistic Screening Of Nearly 6,000 Participants During The May Measurement Month Campaigns 2017-23. J Hypertens. 2024; 42(Suppl 1):E167.
3. Mukosha M, Hatcher A, Mutale W, Lubeya MK, Conklin JL, Chi BH. Prevalence of persistent hypertension following pregnancy complicated by hypertensive disorders in low- and middle-income countries: a systematic review. Front Glob Womens Health. 2024; 5:1315763.
4. R S, Suryavanshi JV, Shedole DT, Dhadave MM. A cross-sectional study on prevalence and risk factors of hypertension among residents of urban field practice area of Gulbarga Institute of Medical Sciences, Kalaburagi, Karnataka, India. Int J Community Med Public Health. 2024; 12(1):330-336.
5. Albab CF, Saputri ON, Andrianto. The Prevalence and Risk Factors of Hypertension Among Adolescents in Southeast Asian Countries: A Systematic Review and Meta Analysis. J Hypertens. 2024; 42(Suppl 2):e5.
6. Cho MJ, Jung YJ, Min HJ, Kim HJ, Kunutsor SK, Jae SY. Sex disparities in physical activity domains and hypertension prevalence. Clin Hypertens. 2024; 30(1):1.
7. Kemeterian Kesehatan Republik Indonesia (Kemenkes RI). Laporan Nasional Riskesdas 2018. Jakarta: Lembaga Penerbit Badan Penelitian dan Pengembangan Kesehatan; 2019.
8. Singh S, Shankar R, Singh GP. Prevalence and associated risk factors of hypertension: A cross-sectional study in urban Varanasi. Int J Hypertens. 2017; 2017(5491838):1-10.
9. YW. Oral drug delivery systems in novel drug delivery pharmaceutical technology. New York: Marcel Dekker Inc.; 1992. p. 139-52.
10. Atre P, Rizvi SAA. Advances in Oral Solid Drug Delivery Systems: Quality by Design Approach in Development of Controlled Release Tablets. BioChem. 2025; 5:9.
11. Tadikonda Rama Rao. Hydrophilic Matrix Tablets As Oral Controlled Drug Delivery Systems In 20th Century: A Review. Int J Adv Res. 2024; 12(8):1372-1393.
12. Roy P, Bhunia A, Ghosh I, Sarkar SUPK, Mondal N, Hossain CM. Swellable hydrophilic matrix tablets for oral drug delivery: Mechanisms, polymer systems, formulation design and future directions. World J Biol Pharm Health Sci. 2026; 26(3).
13. Gokulakrishnan S, Ilango KB, Kalyan R, Samyuktha R, Subash A, Subhashini K. An Innovative Formulation Development Approach of Sustained Release Matrix Tablet: A Review. J Drug Deliv Ther. 2025 Dec 15; 15(12):232-9.
14. Dinesh Kumar Das, Anjan Kumar, Ch. Niranjan Patra. PREPARATION AND OPTIMIZATION OF ONCE DAILY QUETIPINE FUMARATE SUSTAIN RELEASE TABLETS. Asian J Pharm Clin Res. 2026; 62-69.
15. Brunner H. The new oral angiotensin II antagonist olmesartan medoxomil: a concise overview. J Hum Hypertens. 2002; 16(Suppl 2):S13-S16.
16. Brunner HR. Olmesartan medoxomil: current status of its use in monotherapy. Vasc Health Risk Manag. 2006; 2(4):327-40.
17. Scott LJ, McCormack PL. Olmesartan Medoxomil. Drugs. 2008; 68:1239-1272.
18. Kirch W, Püchler K, Laeis P. The pharmacokinetic and metabolic profile of olmesartan medoxomil limits the risk of clinically relevant drug interaction. J Hypertens. 2001; 19:S21-S32.
19. Landry L, Dong X. Investigation of hydrolysis of olmesartan medoxomil in different pH buffers by simultaneously measuring olmesartan medoxomil and olmesartan. PLoS One. 2025 May 2; 20(5):e0321142.
20. El-Dahmy RM, Elsayed I, Hussein J, Althubiti M, Almaimani RA, El-Readi MZ, et al. Development of Transdermal Oleogel Containing Olmesartan Medoxomil: Statistical Optimization and Pharmacological Evaluation. Pharmaceutics. 2023; 15(4):1083.
21. Eid H, Ali A, Salama A, et al. Development of Novel Olmesartan Medoxomil Loaded Leciplex for Enhanced Oral Bioavailability: Formulation, Histopathological Analysis, and In Vivo Pharmacokinetic Studies. J Pharm Innov. 2026; 21:37.
22. Nasr A, Gardouh A, Ghorab M. Novel Solid Self-Nanoemulsifying Drug Delivery System (S-SNEDDS) for Oral Delivery of Olmesartan Medoxomil: Design, Formulation, Pharmacokinetic and Bioavailability Evaluation. Pharmaceutics. 2016; 8(3):20.
23. Zisis C, Pitsikalis M. Blends of linear poly(ethylene oxide) with poly(ethylene oxide) and poly(styrene oxide) brushes. Synthesis, characterization, and study of their thermal properties. Colloid Polym Sci. 2025; 303(12):2481-2500.
24. Abd Elrady AN, Elkhatib MM, Mohamed MI, Fatouh AM. Enhanced buccal bioavailability of olmesartan through ultradeformable bilosomes loaded film: a novel approach for hypertension management. J Liposome Res. 2026; 36(2):142-155.
25. Azharuddin M, Kamath K, Paneerselvan T, Pillai SS, Shabaraya AR. Formulation and evaluation of controlled release matrix tablets of antihypertensive drug using natural and synthetic hydrophilic polymers. Res Biotech. 2011; 2(4):26-32.
26. Kadam RD, Dhembre GN, Jadhao UT, Thoke ST, Rathod DA, Kauthekar VR, et al. Formulation and evaluation of sustained release matrix tablet of ketoprofen. World J Biol Pharm Health Sci. 2024; 20(2):295-304.
27. P SS, G HB, K U, M KB. Formulation, design, and evaluation of valsartan sodium-sustained-release matrix tablets. J Multidiscip Res. 2024; 4(2):1-13.
28. Ganguly D, Choudhury A, Deka H, Sarmah J, Mahanti K, Rahaman SF, et al. A scientific review on Eudragit RS 100 and RL 100 polymer blends for colon-specific oral nanoparticulate drug delivery system. J Appl Pharmacol Toxicol. 2025; 1(1):10-19.
29. Dave VS, Fahmy RM, Bensley D, Hoag SW. Eudragit® RS PO/RL PO as rate-controlling matrix-formers via roller compaction: Influence of formulation and process variables on functional attributes of granules and tablets. Drug Dev Ind Pharm. 2012; 38(10):1240-1253.
30. Zhang Z, Ke F, Wu J, Li X, Chen X, Zhang L, et al. Development of the novel formulations of perospirone for the treatment of schizophrenia. Drug Deliv Transl Res. 2024; 15(6):2162-2178.
31. Kharroubi AT, Darwish HM. Diabetes mellitus: The epidemic of the century. World J Diabetes. 2015; 6(6):850-867.
32. Chang RK, Price JC, Hsiao C. Preparation and Preliminary Evaluation of Eudragit RL and RS Pseudolatices for Controlled Drug Release. Drug Dev Ind Pharm. 1989; 15(3):361-372.
33. Rongthong T, Sungthongjeen S, Siepmann F, Siepmann J, Pongjanyakul T. Quaternary polymethacrylate–magnesium aluminum silicate films: Water uptake kinetics and film permeability. Int J Pharm. 2015; 490(1-2).
34. Narisawa S, Nagata M, Hirakawa Y, Kobayashi M, Yoshino H. An organic acid-induced sigmoidal release system for oral controlled-release preparations. 2. Permeability enhancement of Eudragit RS coating led by the physicochemical interactions with organic acid. J Pharm Sci. 1996; 85(2):184-188.
35. Tsai T, San YP, Ho HO, Wu JS, Sheu MT. Film-forming polymer-granulated excipients as the matrix materials for controlled release dosage forms. J Control Release. 1998; 51(2-3):289-299.
36. Petrie JR, Guzik TJ, Touyz RM. Diabetes, hypertension, and cardiovascular disease: Clinical insights and vascular mechanisms. Can J Cardiol. 2018; 34(5):575-584.
37. Kringeland E, Tell GS, Midtbø H, et al. Factors associated with increase in blood pressure and incident hypertension in early midlife: the Hordaland Health Study. Blood Press. 2020; 29(5):267-275.
38. Abed T, Aly SH, Salim SA, Haikal RR, Shams-Eldin R, EL-Moslamy SH, et al. Optimizing hydrogel performance composed of Japanese pagoda tree extract loaded-gelatin-sodium alginate-polyethylene oxide for biomedical applications: Influence incorporated calcium-based metal organic frameworks and zinc oxide NPs. Int J Biol Macromol. 2025; 310:143526.
39. Muhamad H, Bashir AB, Charlton-Harrison J, Abdulhussain R, Mawla N, Patel K, et al. Hot-melt extruded-FDM 3D-printed polyethylene oxide tablets: Dissolution imaging analysis of swelling and drug release. Eur J Pharm Biopharm. 2025; 208:114636.
40. Chang RK, Hsiao C. EUDRAGIT® RL and RS pseudolatices: properties and performance in pharmaceutical coating as a controlled release membrane for theophylline pellets. Drug Dev Ind Pharm. 1989; 15(2):187-96.
41. González R, Peña MÁ, Torrado G. Formulation and Evaluation of Olmesartan Medoxomil Tablets. Compounds. 2022; 334-352.
42. Gupta H, Sharma M, Ahuja A, Tiwari S. Review on Gastroretentive Systems for Olmesartan Medoxomil. Asian J Pharm Res Dev. 2025; 13(5):126-130.
43. Nagaraj K, Narendar D, Kishan V. Development of olmesartan medoxomil optimized nanosuspension using the Box–Behnken design to improve oral bioavailability. Drug Dev Ind Pharm. 2017; 43(7):1186-1196.
44. Gupta SK, Patra S. Development, Characterization And Pharmacokinetic Evaluation Of Optimized Vildagliptin Sustained Release Matrix Tablet Using Box-Behnken Design. Int J Appl Pharm. 2024; 16(1):214-233.
45. Beckett AH, Stenlake JB. Practical Pharmaceutical Chemistry. 4th ed. New Delhi: CBS Publishers & Distributors; 2023. p. 275-279.
46. International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). ICH Harmonised Guideline: Validation of Analytical Procedures: Text and Methodology Q2(R2). Geneva: ICH; 2023.
47. Stuart B. Infrared Spectroscopy: Fundamentals and Applications. 2nd ed. Chichester: John Wiley & Sons; 2024. p. 55-60.
48. Waterman KC, Adami RC. Accelerated aging: prediction of chemical stability of pharmaceuticals. Int J Pharm. 2005; 293(1-2):101-125.
49. Pasha A, Somashekhar CN. Formulation and evaluation of sustained release matrix tablet of lornoxicam by direct compression method. J Pharm Sci Innov. 2021; 10(5):131-136.
50. Shanmugam S, Srivastav A, Vetrichelvan. Formulation and Evaluation of Sustained Release Matrix Tablets of Venlafaxine Hydrochloride. 2013; 1(5):506-510.
51. Kumari S, Puri A, Dev D, Prasad M. Formulation and evaluation of sustained release matrix tablet of metoprolol succinate by using xanthan gum and Carbopol. 2019; 9:309-316.
52. Alburyhi M, El-Shaibany A. Formulation, Development And Evaluation Of Tribulus Terrestris Extract Capsules Delivery System As An Advanced Phytotherapy Approach For Controlling Diabetes. World J Pharm Res. 2024; 13:1264-1282.
53. Kumbhar DM, Havaldar VD, Mali KK, Dias RJ, Ghorpade VS, Londhe RB. Formulation and Evaluation of Sustained Release Tablets of Venlafaxine Hydrochloride for the treatment of Depressive disorders. Asian J Pharm Res. 2017; 7(1):8-14.
54. Uddin MS, Mamun AA, Tasnu T, Asaduzzaman M. In-process and finished products quality control tests for pharmaceutical tablets according to Pharmacopoeias. J Chem Pharm Res. 2015; 7(9):180-185.
55. Katke NG, Kalshetti MS, Vangari AN, Waghmare OA, Yawalkar NS, Zade MR. A Comparative Quality Control Study of Brand and Generic Amlodipine Tablets by In-Vitro Testing. Int J Sci Res Sci Technol.
56. Akhtar MF, Rabbani M, Sharif A, Akhtar B, Saleem A, Murtaza G. Formulation and characterization of modified release tablets containing isoniazid using swellable polymers. Afr J Tradit Complement Altern Med. 2011; 8(3):250-9.
57. The United States Pharmacopeial Convention. USP. 2011.
58. Kadam RD, Dhembre GN, Jadhao UT, Thoke ST, Rathod DA, Kauthekar VR, et al. Formulation and evaluation of sustained release matrix tablet of ketoprofen. World J Biol Pharm Health Sci. 2024; 20(2):295-304.